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ine COPREEG TED PAPERS 


OF 


JOSEPH, BARON LISTER 


PUBLISHED BY 
HENRY FROWDE, M.A. 
OXFORD UNIVERSITY PRESS 


AND 


HODDER AND STOUGHTON 
WARWICK SQUARE, E.C. 


LONDON 


4 
THE COLLECTED PAPERS 


OF 


JOSEPH, BARON LISTER 


MEMBER OF THE ORDER OF MERIT 
FELLOW AND SOMETIME PRESIDENT OF THE ROYAL SOCIETY 
KNIGHT GRAND CROSS OF THE DANISH ORDER OF THE DANEBROG 
KNIGHT OF THE PRUSSIAN ORDRE POUR LE MERITE 
ASSOCIE ETRANGER DE L’INSTITUT DE FRANCE 
EEC) EXC. 


IN TWO VOLUMES 


VOL. I 
_— 
Lay 
Ate 
a 4\ 
AN 
a 
OXFORD 


AT THE CLARENDON PRESS 


MDCCCCIX 


OXFORD 
PRINTED AT THE CLARENDON PRESS 
BY HORACE HART, M.A. 
PRINTER TO THE UNIVERSITY 


PREFACE 


WHEN, on the 5th of April, 1907, Lord Lister attained his eightieth birthday, 
he was the recipient of many congratulations, not only from his fellow country- 
men, but from representatives of medicine and surgery throughout the world, 
and a unanimous desire was then expressed that some permanent memoria] 
should be instituted of so happy an occasion, and of a life so rich in benefits to 
mankind. 

No memorial seemed more appropriate than a collected edition of his scien- 
tific papers, scattered through many different periodical publications, inasmuch 
as in them are recorded the steps by which the great revolution in surgery with 
which his name will be imperishably associated was brought about, and by 
their perusal succeeding generations may learn at first hand the great principle 
on which that revolution was based. The proposal, it was ascertained, com- 
mended itself to Lord Lister, and the Committee which has prepared these 
volumes for the press has had the inestimable advantage of his guidance and 
advice. 

The two volumes contain all the papers and addresses which he himself 
considers to possess permanent interest and importance ; the omissions in fact 
are few in number, and consist almost solely of addresses on certain official 
occasions dealing with matters of ephemeral or merely local interest. The 
papers have been classified under four general heads, according as they deal with 
Physiology, Pathology and Bacteriology, the Antiseptic System, or General 
Surgery, while various general addresses and lectures are gathered together 
in a fifth part. In arranging the several papers in each Part chronological 
order has generally been followed. 


The Committee has thought it well to preface the text of the papers and 


vi PREFACE 


addresses themselves by a brief introduction giving some account of the state 
of surgery at the date when Lord Lister began his work, indicating the growth 
of the principle by which he was guided, and tracing the early stages of its 
application to practical surgery. Without some such preliminary statement, 
those unacquainted with the position of surgery, and the conditions prevalent 
in surgical wards in the middle of the nineteenth century, may fail adequately 
to understand the difficulty and complexity of the problem as it presented 
itself to him, and the brilliancy of the long chain of reasoning and experiment 


by which he was led to its triumphant solution. 


NOTE 


These volumes were prepared for the press by a Committee consisting of : 
Sir Hector C. Cameron. 
Sir W. Watson Cheyne, Bt., C.B., F.R.S. 
Rickman J. Godlee, M.S. 
Gi). Martin’. MAD nS: 
Dawson Williams, M.D., F.R.C.P. 


(evo OF CONTENTS 


VOLUME I 


PAGE 
PREFACE ., i ‘ : : : : : . ; ; ; V 
INTRODUCTION ; ; : ; : . : : : , : . Xi 


Pas ly PHYSIOLOGY 


Observations on the Contractile Tissue of the Iris . ; ; ; ‘ : : I 
Quarterly Journal of Microscopical Science, vol. i (1853), p. 8. 


Observations on the Muscular Tissue of the Skin . : : ‘ ; : . : 9 
Ibid., p. 262. 
On the Minute Structure of Involuntary Muscular Fibre : . 15 


Transactions of the Royal Society of Edinburgh, vol. xxi, P; urt IV (1857), p. 549. 


On the Flow of the Lacteal Fluid in the Mesentery of the Mouse. : : : _ 2 
Report of the Meeting of the British Association, Dublin, 1857, p. 114. 


An Inquiry regarding the Parts of the Nervous System which regulate the Contractions of 
the: Arteries |, : : ; ; : : : ; : : - @ 
Philosophical ae acon Part II for 1858, p. 607 (read June 18, 1857). 


On the Cutaneous Pigmentary System of the Frog . : : : : a: : - 48 
Ibid., p. 627 (read June 18, 1857). 


On Spontaneous Gangrene from Arteritis and the Causes of Coagulation of the Blood in 
Diseases of the Blood-vessels. 
Edinburgh Medical Journal, April 1858. 


A Case of Ligature of the Brachial Artery, illustrating the Persistent Vitality of the Tissues 
Ibid., vol. iv, p. 119, August 1858. 


Preliminary Account of an lee into the Functions of the Visceral Nerves, with special 
Reference to the so-called * Inhibitory System ’ : : 
Proceedings of the Royal Soctety of London, vol. 1x, Ro: 32 (1858). 


Some Observations on the Structure of Nerve-fibres (jointly with Sir William Turner) - — 99 
Quarterly Journal of Microscopical Sctence, October 1859. 

Notice of further Researches on the Coagulation of the Blood . 
Edinburgh Medical Journal, December 1859. 


On the Coagulation of the Blood. The Croonian Lecture delivered before the Royal Society 


of London, June 11, 1863 , 
Proceedings of the Royal Society of Deion 186 3. 


On Anaesthetics. Part I written 1861, Part II written 1870, Part III written 1552 
Holmes’s System of Surgery, vol. iii, third edition. London, 1853 


Vill CONTENTS 


Effects of the Position of a Part on the Circulation through it . . ° : - - 
British Medical Journal, 1879, vol. 1, p. 923. 

On the Application of a Knowledge of Hydrostatics and Hydraulics to Practical Medicine . 
Lancet, 1882, vol. ii, p. 638. 


On the Coagulation of the Blood in its Practical Aspects. The Annual Oration to the Medical 
Society of London, delivered May 4, 1891 : : ‘ ; ‘ : : 4 
British Medical Journal, 1891, vol. i, p. 1057. 


PART II. PATHOLOGY AND BACTERIOLOGY 


Notes of the Examination of an Exostosis removed by Mr. Syme on October 2, 1853, from the 
Os Humeri of a young Lady aged about Twenty Years. . - 4 : ° 
Monthly Journal of Medical Science, January 1854. 


Report of a Case of Carbuncle occurring in Mr. Syme’s Practice, illustrating especially the 
Pathology of that Disease 
Iitd., July 1854. 


. 


On the Early Stages of Inflammation 
Philosophical Transactions, Part II for 1858, Dp: a fend dame 18, 1857). 


A Contribution to the Germ Theory of Putrefaction and other Fermentative Changes, and to 
the Natural History of Torulae and Bacteria 
Transactions of the Royal Society of Edinburgh, ll XXVU, 7875 cod April os 1873). 


A further Contribution to the Natural History of Bacteria and the Germ Theory of Fermenta- 
tive Changes 


Quarterly Journal of Macsoscnece! Serene. lOelanes 7875. 
On the Nature of Fermentation. The Introductory Address delivered in King’s Ce 


London, at the Opening of the Session, October 1, 1877 
Quarterly Journal of Microscopical Science, April 1878. 


On the Lactic Fermentation and its Bearings on Pathology (delivered December 18, 1877) . 


Transactions of the Pathological Society of London, vol. xxix, 1878. 


On the Relations of Micro-organisms to Disease. An Address delivered before the Pathological 
Section of the British Medical Association at Cambridge, August 12, 1880 
Quarterly Journal of Microscopical Science, April 1881. 


An Address on the Relations of Minute Organisms to Inflammation, delivered in the Patho- 
logical Section of the International Medical Congress, August 5, 1881 
Transactions of the International Medical Congress, London, 1881. 


PAGE 


186 


189 


201 


206 


209 


275 


309 


335 


353 


387 


399 


LisT OF PLATES IN VOL. I 


PORTRAIT OF LorRD LIsTER. From a photograph taken in Edinburgh in 1856 . Frontispiece 
Pai ot 
To face page 
(To illustrate ‘ Observations on the Contractile Tissue of the Iris’ ) 
"(To illustrate ‘ Observations on the Muscular Tissue of the Skin’ F ; : jo 
II. Two-page plate to Ulustrate ‘On the Minute Structure of Involuntary Muscular Fibre’ 24 
III. To illustrate ‘On the Cutaneous Pigmentary System of the Frog’. . 68 
IV. To illustrate ‘Some Observations on the Structure of Nerve-Fibres’ : , . 104 
PAK Ter 
V. To illustrate ‘On the Early Stages of Inflammation’ 274 
VI. 
| 
VIII. ‘ To illustrate ‘A Contribution to the Germ Theory of Putrefaction’ . . 308 
IX. | 
4 
XII.- To illustrate ‘A Further Contribution to the Natural History of Bacteria’ . - 334 
CUE: 


XIV. To illustrate ‘On the Lactic Fermentation’ : : : ; ; . 386 


CHRONOLOGICAL NOTE 


Born April 5, 1827. 

Graduated B.A. 1847, M.B. 1852, University of London. 

Edinburgh: House Surgeon, 1854; Extra-Mural Lecturer, 1855, and Assistant 
Surgeon, Royal Infirmary, 1856. 

Glasgow: Professor of Surgery, 1860-9. 

Edinburgh : Professor of Clinical Surgery, 1869-77. 

London: King’s College, Professor of Clinical Surgery, 1877-93. 


INTRODUCTION 


IT is not proposed to enter into any biographical details in the following 
notes, which are merely intended to indicate the sequence of events in the course 
of Lord Lister’s work, and thus to enable the reader to follow the development of 
his great discovery. His work was carried out at different periods and under 
the varying circumstances of different hospitals and clinical schools. 

The first of these periods was one of preparation, ending in his graduation 
in medicine at the University of London in 1852. Among the men whose 
influence during this period was of the greatest importance in determining 
his future line of thought and work were his father, Joseph Jackson Lister, 
William Sharpey, Professor of Physiology, and Thomas Graham, Professor 
of Chemistry in University College. 

Joseph Jackson Lister was a merchant in the City of London who devoted 
his leisure to scientific pursuits, and especially to the perfecting of the microscope, 
and his name will always be remembered as the first to solve the problem of the 
production of achromatic lenses. He was a man of extreme accuracy of thought, 
a most methodical worker, a good classical scholar, and skilful with brush and 
pencil. His influence on his son’s character and career was very great. This 
has been acknowledged with gratitude by Lord Lister himself, not only in the 
obituary of his father, reprinted in the second of these volumes, but also on 
many other occasions. 

During his career at University College, Lister came specially under the 
influence of Sharpey, and under his guidance early applied himself to the study 
of various physiological problems. Papers describing the results of three 
important researches made by him at this period are reproduced in this volume. 
They relate to the contractile tissue of the iris, to the muscular tissue of the 
skin, and to the flow of lacteal fluid in the mesentery of the mouse respectively. 
His keen interest, too, in the study of chemistry under Graham had an abiding 
effect, for it equipped his mind with a sound knowledge of the principles and 
methods of chemical science, which greatly aided him in many ways in his 
future researches, not least in devising various forms of antiseptic dressings, 
a task which entailed great labour and patience in the conduct of a long 
series of experiments extending over many years. 

The second of the periods referred to was that of his first residence in 
Edinburgh (1852-60). After completing his course at University College, and 


Xi INTRODUCTION 


his time of residence in University College Hospital as House Physician and 
House Surgeon with Dr. Walsh and Mr. Erichsen respectively, he went to 
Edinburgh, taking an introduction from Dr. Sharpey to James Syme, Professor 
of Clinical Surgery in the University, on what was intended to be only a short 
visit. Asa matter of fact, however, this visit led to Lister’s settling in Edinburgh, 
where he remained until he received a call to occupy the chair of surgery in the 
University of Glasgow. Lister appears at once to have conceived a great admira- 
tion for Syme, then at the zenith of his great powers as a clinical teacher. He 
respected not only Syme’s skill and resource as an operator, but also the strength 
of his intellect and the soundness of his judgement. Syme formed a just estimate 
of the powers of his visitor, for on a vacancy unexpectedly occurring he appointed 
Lister his House Surgeon in the Edinburgh Royal Infirmary. This association 
resulted in a warm personal friendship, which was cemented by Lister’s marriage 
a few years later with Syme’s eldest daughter, a lady who to the end of her life 
was indeed her husband’s helpmeet in all his scientific investigations. 

Lister became successively Lecturer in Surgery in the Extra-Mural School, 
and Assistant Surgeon to the Royal Infirmary, and held these appointments 
at the time of his translation to Glasgow. The work which Lister did during this 
period of his life, and the direction of his thoughts, cannot be better indicated 
than by a glance at the writings he then published. The earliest papers were 
on the duration of vitality in the tissues, on the structure of involuntary muscular 
fibre, and on the cutaneous pigmentary system of the frog. Another group of 
papers dealt with the early stages of inflammation, with gangrene from arteritis, 
and with the coagulation of the blood both within and without the blood-vessels, 
while a third group was concerned with the nervous system and included obser- 
vations on the functions of the visceral nerves, with special reference to the 
inhibitory system, on the parts of the nervous system regulating the contraction 
of the arteries, and on the structure of nerve-fibre. It is not difficult to perceive 
the interrelation of these several lines of study and investigation, and the perusal 
of the papers in which they are embodied affords an interesting example of 
acute reasoning applied to the interpretation of the results of accurate observa- 
tion and experiment. 

The third distinct period of Lord Lister’s life was that during which he 
occupied the chair of Systematic Surgery in the University of Glasgow (1860 
to 1869). He there found himself in charge of a large number of beds 
in the old Royal Infirmary, to which, serving as it did the requirements 
of a great manufacturing city, accidental wounds of all sorts and degrees 
were daily admitted. From its wards, as he has related in the papers on the 
effects of the antiseptic system upon the salubrity of a general hospital here 


INTRODUCTION Xlil 


republished,’ septic diseases were seldom absent, and the mortality from 
wounds and after all surgical operations was enormous. At the beginning 
of his career in Glasgow we find him continuing his work on the coagulation of 
the blood, the subject to which he devoted the Croonian Lecture delivered before 
the Royal Society in 1863 ; but he published also several important contribu 
tions to practical surgery, including the introduction of a new method of 
excising the wrist-joint, and the preparation of articles on anaesthetics and on 
amputation for Holmes’s System of Surgery 

But the gravity and constant prevalence of septic diseases in his wards, and 
the distressing mortality which occurred in consequence thereof, often in the most 
promising cases, so disappointed, pained, and distressed him, that his thoughts 
became more and more turned to the question of the cause and prevention of 
these disasters. Very many methods were tried in the hope of improving the 
treatment of wounds and the salubrity of his wards, for he was not satisfied 
to accept the fatalistic view then prevalent that septic diseases of wounds were 
unavoidable incidents, as much acts of God as a hail in harvest, and matters, 
therefore, in regard to which the surgeon had no personal responsibility. It 
was out of this divine discontent with things as they then were that there grew 
up the great work of his life, the introduction of the antiseptic method of wound 
treatment. During the remainder of this period of his life the majority of the 
papers he published were concerned with this subject, and others, such as those 
on the methods of ligaturing blood-vessels and stitching wounds, hada direct and 
essential bearing upon it. While his main aim was from the first and always the 
prevention of sepsis in wounds, he at the same time recognised, equally from the 
beginning, the importance of diminishing and as far as possible neutralizing the 
irritation of the wound and the general toxic effects which might be produced 
by the chemical substances employed as antiseptics. 

The fourth period in his life was that during which he occupied the chair 
of Clinical Surgery in the University of Edinburgh. To this he was appointed 
by the Crown on the resignation of Mr. Syme. He assumed its duties at the 
beginning of the winter session of 1869. Already in Glasgow the soundness 
of the principles on which he was proceeding had been thoroughly established, 
but the methods by which those principles were carried into practice were still 
cumbrous and far from perfect ; during his incumbency of the Edinburgh Chair 
he was largely occupied in devising and testing improvements in the methods of 
carrying out the antiseptic principle, with the object of rendering its use in 


* Vol. li, pp. 123 and 156. 
2 These articles, revised at a later date, are reprinted by permission of Messrs, Longmans at p. 135 
of this volume, and p. 378 of volume ii. 


X1V INTRODUCTION 


everyday practice simpler. The writings published during this period are, as 
will be seen by reference to the second volume, chiefly devoted to such matters. 
At the same time he carried out investigations and published papers on other 
allied subjects, as, for example, on the germ theory of putrefaction, and on 
lactic fermentation. 

The last period of Lister’s active life dated from 1877, when he went to 
London in response to an invitation from the authorities of King’s College, 
to fill the chair of Clinical Surgery in succession to Sir William Fergusson. 
This period, which extends until his retirement from active surgical work in 
1892, may be characterized as one in which the final details of antiseptic surgery 
were more or less perfected. Various fresh antiseptics were tested, especially with 
the view of obtaining some antiseptic dressing which, while as reliable as the 
carbolic gauze, might yet prove less directly irritating, and being non-volatile 
might be trusted for longer periods, thus avoiding the necessity for frequent 
change of dressings and disturbance of the wounds. During this period, his 
method of treatment approximated more and more to his ideal of converting 
open wounds, as regards their subsequent course, to the condition of sub- 
cutaneous injuries. 

These preliminary remarks cannot be more appropriately brought to a 
close than by a reference to the unwearied help that Lady Lister afforded to her 
husband in the pursuit of his investigations throughout her life. Those who 
were admitted to the inner circle can never forget the vivid interest which she 
took in the details of his work, and the many closely written volumes of dictated 
notes in her handwriting containing full records of the experiments on which 
the conclusions expressed in the essays reproduced in these volumes were 
largely founded. 


PHYSIOLOGICAL AND PATHOLOGICAL WORK 


In his Huxley lecture,’ delivered in 1900, Lord Lister has given an account 
of some of his early physiological researches. In it he dwelt particularly on 
those researches which were more intimately connected with the development 
of his ideas upon the nature and causation of inflammation and suppuration. 

From this account it can be seen how Lister’s ideas of these processes 
gradually matured. It wanted only the conception of infection to complete 
them, and this was supplied in Pasteur’s discovery of the causation of putre- 
faction, the full significance of which Lister was thus able at once to realize. 

This chapter of scientific discovery could hardly have been more pleasingly 


po eb et oat na 


INTRODUCTION XV 


told than by the author himself, so that it is here only necessary briefly to 
review Lister's principal investigations in physiology and pathology as con- 
tributions to these sciences. 

It is not surprising that Lister’s first investigations should have been 
histological. His father, Joseph Jackson Lister, who had by his optical experi- 
ments very greatly improved the compound microscope, was an accomplished 
microscopist and made important discoveries concerning the structure of zoo- 
phytes and acidians. At this period the theory of the microscope was being 
rapidly developed, and each consequent improvement in this instrument of 
research opened up further fields to the investigator. Kdlliker had recently 
discovered the cellular structure of plain muscular tissue and the first investiga- 
tions of Lister were concerned with the contractile tissue of the iris! and skin?, 
and with the structure of involuntary muscular fibre generally.2 The observa- 
tions and conclusions of Kolliker were at this time by no means universally 
accepted, but Lister’s work not only vindicated their accuracy, but cleared 
away many apparent discrepancies between the observations of different 
observers. He also made a number of new observations upon the structure 
and distribution of smooth muscle fibres. These three papers were illustrated 
by excellent camera-lucida drawings made by Lister himself, which are repro- 
duced in the present volume. 

At the time when the last of these papers was written Lister had already 
commenced an inquiry into the process of inflammation,’ a subject to which 
he seems to have been irresistibly attracted from the first ; around it, hence- 
forth, almost all his researches centred, although he often made wide excursions 
to investigate physiological problems encountered in efforts to interpret some 
one or other of the processes concerned in inflammation. 

The investigation of the nature of the process of inflammation was, tor 
the most part, made by direct observation upon the frog’s web, a method 
which permitted the study of the phenomena from the beginning. Therein 
lay its great fertility. His observations were, however, carefully controlled 
by observations made upon the higher animals and man. The phenomena ot 
stasis, and the vascular reaction, immediate and subsequent, following the 
application of irritants of all classes were for the first time accurately described. 
The former was shown to be due to the direct action of the irritant upon the 
blood-cells and blood-vessels, and the latter to be occasioned reflexly through the 
nervous system. These observations upon the early stages of inflammation were 
communicated to the Royal Society in 1857. They have formed the basis of 
all subsequent discoveries, and the conclusions drawn are as valid to-day as then. 


Vol dy ps 3. 2 Vol. i, p. 9. #NW6l.4, Ds 18. Vol. 1, p. 200. 


xv INTRODUCTION 


The vascular reaction to irritation was found by Lister, as has been said, 
to be indirectly produced through the medium of the central nervous system. 
That the calibre of the arteries was controlled by the nervous system had 
recently been established by Claude Bernard’s discovery that section of the 
cervical sympathetic was followed by dilatation of the blood-vessels in the 
head and neck, and Waller’s observation that stimulation of this nerve caused 
constriction in the same area. Waller and Budge also had just shown that 
the fibres of the cervical sympathetic, stimulation of which occasioned con- 
striction of the vessels, emanated from the upper dorsal region of the spinal 
cord. On the other hand, Wharton Jones had stated that whilst division of 
the sciatic nerve was followed by extreme dilatation of the vessels in the 
frog’s web, section of the roots of the sciatic within the spinal canal failed to 
produce this effect, whence he inferred that the constrictor fibres in the sciatic 
trunk came not from the cord but from the ‘Sympathetic system’. 

Lister, who was no doubt interested in the control of the calibre of the 
blood-vessels primarily on account of his observations upon the vascular reaction 
in inflammation, proceeded to make an investigation to ascertain which parts 
of the nervous system regulated the contraction of the arteries,! with the 
view of clearing up the apparent discrepancy suggested by the observations 
of Waller and Budge and Wharton Jones respectively. 

The experiments were made upon the frog, and the size of the vessels of 
the web directly observed and measured by an eyepiece-micrometer. Both 
webs were simultaneously under observation, sothat when the nervous connexions 
of the one side were interfered with, the other served as a control. With this 
simple technique he conducted a series of experiments, which even at the 
present time could not fail to excite admiration on account of the simple 
directness of their conception and the ingenuity with which they were carried 
out. He showed how Wharton Jones was led to a false conclusion, and estab- 
lished the fact that the fibres controlling the calibre of the vessels in the web 
of the frog issue from the spinal cord, as do those through which sensation 
and motion are effected in the hind limbs. He further demonstrated that the 
greatest focus whence those fibres emerged was at the posterior end of the cord, 
so that if this portion of the spinal axis were removed, intense dilatation ensued. 
Unless, however, the amount of cord removed was extensive, after an interval 
of some days the vessels recovered to some extent their former calibre, showing 
that the supply is not absolutely confined to any limited region. Experiments 
on frogs in which the whole nervous system had been destroyed, and upon 
amputated limbs also, led him to conclude that there must in addition be © 


1 Vol. 1, p27. 


INTRODUCTION XVil 


a local co-ordinating mechanism, but that this local mechanism was dominated 
by the central nervous system. 

In the course of these investigations Lister had under frequent observation 
the stellate pigment-cells of the frog’s skin, the concentration and diffusion 
of the chromatophorous particles within which produce the temporary varia- 
tions in colour of the animal. The diffusion of the particles throughout the 
stellate cells causes the tint to darken, whereas their concentration in the body 
of the cell produces the opposite effect. Lister noticed that when the animal 
struggled, the particles moved suddenly and energetically in the direction of 
the body of the cell, as if acted upon by some stimulus. Convinced that he 
was observing a vital phenomenon of great physiological importance, he deter- 
mined to investigate it. 

Von Wittich had found that the process was under the influence of the 
nervous system and that the sciatic nerve contained fibres which controlled 
the condition of the pigment-cells of the hind limbs. Lister confirmed these 
observations and further succeeded in demonstrating the mechanism of control, 
and showed that the adaptation of the colour of the frog to its surroundings 
was brought about reflexly by light entering the eye. 

Lister also made observations of the first importance upon the nervous 
mechanism of the musculature of the gut.2, These experiments were primarily 
undertaken to test Pfliiger’s conclusion that the splanchnic nerves contained 
special inhibitory fibres distributed to the muscular coats of the intestine. 
Lister verified Pfliiger’s results, but did not accept his interpretation. He 
came to the conclusion that both the observations of Pfluger and his own 
experimental results were not inconsistent with the view that the same fibres 
produce increased and diminished muscular activity, according to the strength ot 
the stimulus impressed upon them. Although later work has justified the inter- 
pretation of Pfliiger, the experiments devised by Lister to test this hypothesis led 
him to important conclusions regarding the mechanism of intestinal movements, 
namely, that there was an intrinsic nervous apparatus which co-ordinated the 
movements of successive muscular fibres in peristalsis, and that the latter could be 
stimulated or checked by impulses coming from other parts of the nervous system. 

Another department of physiology to which Lister made considerable con- 
tributions was the causation of the coagulation of blood.’ His attention seems 
to have been drawn to this subject by the coagulation of blood in an inflamed 
artery, and the question presented to him was, why does blood clot in contact 
with an inflamed vascular wall, whereas it remains fluid when surrounded by 
healthy endothelium ? 

TeVol. a: p- 48. * Vol. i, p. 87. * Vol. i, pp. 69, 105, 109, and 189. 


LISTER I b 


xvii INTRODUCTION 


At this time knowledge of physiological chemistry was but little advanced. 
It is only now, fifty years after Lister’s work, that we are beginning to arrive 
at an adequate interpretation of the complicated phenomena of coagulation, 
and that an answer to the question with which Lister was confronted is 
forthcoming. At that date all that could be vouchsafed to the most patient 
and gifted experimenter was to remove false conceptions and accumulate 
a number of accurate observations to serve as guide-posts for future workers. 
This Lister accomplished. He showed the untenability of the then prevalent 
theory of Richardson that coagulation was due to the escape of ammonia when 
blood was shed. Both in so doing and afterwards in seeking for an explanation 
why blood should comport itself so differently when in healthy living vessels, 
and when in contact with ordinary solids, he discovered a large number of 
cardinal facts concerning coagulation which have been, and will in the future 
still be, of service to investigators in their efforts towards complete under- 
standing of the phenomena of the clotting of blood. 


SURGICAL WORK 


A just conception of the value of Lister’s surgical work can only be formed 
if the state of surgery and the conditions of surgical practice towards the middle 
of the last century are borne in mind. The results of surgical operations are 
now so generally good that it is hard to realize what they were before Lister 
began his reform. At that time, though they naturally varied a good deal 
in different hands and under different sanitary conditions, the broad facts 
with regard to the very unsatisfactory results of the surgical treatment 
of wounds and the dangers of operations were much the same in every 
country and in every hospital. Putrefaction of the discharges present in and 
escaping from the wounds occurred in almost every case, and was accompanied 
by more or less local inflammation. Wounds were, during their early stages, 
swollen and painful, and this local inflammation was constantly attended by 
more or less fever, which usually lasted for several days. Union by first in- 
tention was of very rare occurrence ; it was indeed impossible in large wounds, 
owing to the fact that the ligatures with which the vessels were tied had 
subsequently to be extruded by a process of granulation and suppuration ; the 
suppuration which necessarily occurred along the track of the ligatures usually 
spread to the rest of the wound. Associated with this process of separation of 
the ligatures was another danger, from the dread of which the surgeon’s mind 
was never free: this was the fear that the process by which this separation was 
brought about might open up the lumen of the vessel, and lead to so-called 
secondary haemorrhage. 


+ 


INTRODUCTION X1X 


Still more serious than these local troubles was the frequent occurrence of 
general septic diseases, such as septicaemia, pyaemia, erysipelas, tetanus, or 
hospital gangrene. In a large proportion of the cases in which a wound of 
any considerable size was produced, whether by an accident or by the surgeon’s 
knife, the patient suffered more or less severely from one or other of these surgical 
diseases. After major amputations, for example, the mortality was very high 
the average in the practice of various surgeons at that time varied from 30 to 50 
per cent. Lister collected his statistics of amputation for two years (1864 and 
1866), just before he introduced the antiseptic method of treatment, and found 
the mortality to be 45 per cent.1 The causes of death are not definitely stated, 
but almost all the deaths were due to infective diseases ; for example, of six deaths 
following amputation of the upper extremity four were due to pyaemia and 
one to hospital gangrene. In his paper on excision of the wrist-joint, published 
in 1865, he refers to fifteen cases in which he had performed this operation, 
and incidentally remarks that six were attacked by hospital gangrene, while 
one died of pyaemia.? 

Volkmann, in one of his earliest papers * on antiseptic treatment, stated that 
for the four years preceding the adoption of Lister’s method, that is down to 
1872, he had left his wounds entirely open. During the first year in which this 
method was carried out, the results were very favourable, and he was thoroughly 
convinced of its superiority over the plans which he had formerly adopted. As 
time went on, however, and as overcrowding of the wards became unavoidable, 
infective diseases of wounds increased progressively, and at last, in the sum- 
mer and autumn of 1871, the deaths from pyaemia and septicaemia were so 
numerous that he made up his mind to close the hospital altogether for a 
time. Before resorting to this desperate remedy, however, he determined to 
try the Listerian method for a few weeks, and the result of this trial was 
entirely to alter the aspect of affairs. 

Similar facts were published by Nussbaum of Munich, who commenced the 
treatment two years later than Volkmann. The hospital at Munich, a building 
by no means satisfactory as regards sanitary arrangements, became a hot-bed 
of septic infections to so great an extent that almost every case of open wound 
was attacked by one or other of these diseases. Pyaemia was rife, affecting 
nearly all cases of compound fracture, wounds of bones, and amputations. 
Erysipelas was constantly present. During 1872 hospital gangrene also appeared, 
and steadily spread in spite of all the precautions which experience dictated 
or ingenuity could devise; in that year 26 per cent. of all the wounds were 
attacked by this dreaded disease; during 1873 the proportion increased to 


* See vol. li, p. 129. 2 See vol. ii, p. 440 * Beitydge sur Chirurgie. 


b2 


XX INTRODUCTION 


50 per cent., and it ultimately reached 80 per cent. Erysipelas, too, which 
in 1872 was of a comparatively mild type, became much more virulent as well 
as more frequent. All this occurred in spite of the use of antiseptic lotions, 
of the open method, and other devices. In 1878, after he had put Lister’s method 
to the test of practice, Nussbaum published an essay entitled Sonst und Jetzt, in 
which he drew the following striking contrast between the previous state of 


affairs and that which followed the introduction of Listerism : 
Formerly. Now. 

Injuries of the head, compound fractures,ampu- 

tations and excisions, in fact almost all patients in 

whom bones were injured, were attacked by pyaemia. 

For example, of 17 cases of amputation 11 died from 

this cause. Even patients with severe whitlow died 

from it. No pyaemia. 
Hospital gangrene had got the upper hand to 

such an extent, that in spite of the open method, in 

spite of continuous water-baths, in spite of the use of 

chlorine water, or the actual cautery, finally 80 per 

cent. of all wounds and ulcers were attacked, large 


arteries being opened into. No hospital gangrene. 
Almost every wound was attacked with ery- 
sipelas. No erysipelas. 


It would be easy to produce a great cloud of witnesses to the appalling state 
of matters in various hospitals before the introduction of the Listerian method, 
but their testimony would merely be a repetition of the above statements. Itis 
true that these untoward results were witnessed most often and in their direst 
form under hospital conditions of a particularly insanitary kind, and that their 
frequency and severity varied considerably, according to the methods of wound 
treatment adopted. Nevertheless these infective diseases were present every- 
where, and it will readily be understood that the dread of them, never absent 
from the surgeon’s mind, was a serious bar to progress. 

Further, the operations undertaken in those days were very different from 
those now commonly performed. Surgical intervention was then limited 
more or less entirely to operations absolutely necessary for the saving of life. 
Operations of expediency, designed to add to the patient’s comfort or to make 
his life more useful, were not deemed justifiable owing to the probability of the 
onset of some form of infection, and the consequent risk of the development of 
one of the severe general infections which so frequently ended in death. The 
major operations then performed were for the most part amputations for 
injury and disease, excision of joints, amputation of the breast, removal of 
tumours, operations on the jaw and tongue, trephining, operations for strangu- 


INTRODUCTION XX1 


lated hernia, operations on the urinary organs, and certain plastic operations. 
Abdominal surgery, as we now understand it, did not exist, the extensive opera- 
tions for malignant growths and tuberculous disease now generally practised 
were not performed, and the numerous exploratory operations undertaken at 
the present day were not even contemplated. In fact, modern surgery dates 
from the introduction of the Listerian methods. 


The treatment of wounds as practised at different periods varied greatly, 
according to the views taken by different surgeons as to the causes of the septic 
troubles which were so prone to arise. But until Lister framed and began to 
test the antiseptic hypothesis, the whole subject of the diseases of wounds was 
in a State of chaos. 

It may be interesting to mention some of the chief methods of wound treat- 
ment in vogue during the early part of the nineteenth century. At that time 
the air was looked on as the cause, in some way or other, of the troubles resulting 
from wounds, and many surgeons attempted to exclude it by putting on great 
masses of dressings and ointments. A reaction against this method of treatment 
set in, leading to the development of what was called the open method of treating 
wounds. In that plan the wound was left freely open, no more being done than 
to provide means for allowing the discharges to flow freely away, and to prevent 
contact of clothing. This gave results in many ways superior to those obtained 
from methods previously in vogue. 

Another plan which also furnished good results and is still employed in 
suitable cases, was constant irrigation of wounds with water, or the immersion 
of the wounded part in a water bath. The bath gave excellent results in the 
hands of Vallette and others, especially when combined with the use of various 
substances which we now know to possess antiseptic properties, such as tincture 
of benzoin, creosote, and iron salts. 

About this time also subcutaneous surgery was introduced, but unfor- 
tunately it was a method applicable only in a very limited number of cases. 
John Hunter had at an earlier date pointed out the advantage of healing by 
scabbing, and to obtain this became a frequent object in the treatment of 
small wounds. Nevertheless the most common method of treating wounds 
was, perhaps, by a water dressing, a piece of lint dipped in water being applied 
over the surface of the wound, and covered by oiled silk. This method led to 
putrefaction and suppuration in the wound in the great majority of cases. 

Shortly before Lister began his work some surgeons had begun to employ 
various substances, with the avowed intention of diminishing the putrefaction 
of the discharges in wounds. Among the materials thus employed were alcohol, 


XXil INTRODUCTION 


glycerine, chlorine compounds, iodine, chloride of iron, coal-tar preparations, 
and even carbolic acid. But the methods followed in the employment of these 
substances were imperfect, and, not being founded on any precise knowledge of 
the causes of putrefaction, they failed to ensure the desired result. 

The method which Lister himself employed before he took up antiseptic 
work is thus described by Sir Hector Cameron, who was his dresser and house 
surgeon at the time he began his antiseptic work :— 


He was in the habit at this time of treating all recent wounds by the 
simple plan which had been for many years taught and practised by Mr. Syme 
in the Edinburgh Hospital. After the principal arteries had been secured by 
ligaturing them with well-waxed silk strings, and smaller bleeding-points were 
arrested by torsion as originally suggested by Amussat, two folded pads of lint 
were placed on each side of the lips of the wound so as to exercise pressure, while 
a larger piece of the same absorbent material was placed over these, and secured 
by a fairly firm bandage. Drainage was effected by bringing the ends of the 
long silk ligatures out at one or both ends of the wound, and the sutures used 
were of silver wire. This dressing was left undisturbed for several days, unless 
a complaint of pain or a quickened pulse demanded earlier interference. Occa- 
sionally, union by first intention occurred except in the tracks of the ligatures, 
but so long as these remained there was no security against the supervention of 
one or other of the many hospital diseases which were always present in the 
wards. More often the wound—whatever its original nature—inflamed and 
suppurated freely ; it was then treated either with water dressing covered by 
gutta-percha tissue, or poulticed with linseed-meal poultices. In either case, 
the coverings of the wound were frequently changed, and at each renewal the 
pus was squeezed out as thoroughly as possible (counter openings being made 
if necessary), and the wound well washed with a mixture of warm water and 
Condy’s Fluid, usually poured out of a kettle. Lister soon began to enjoin on 
all persons in his clinique the practice of scrupulous cleanliness, which was at 
that time by no means always a characteristic of surgical practice. The washing 
of hands was insisted on after dressing each individual case, and large piles of 
clean towels stood on the tables of his wards for the use of his dressers and nurses. 

In consequence of the reported results of some experiments on dogs by Polli 
of Milan, he tried at this time the free exhibition of sulphite of soda or potash in 
solution as a cure and also as a prophylactic of pyaemia and other septic diseases. 
Every patient operated on or admitted to his wards with a wound had this 
remedy administered to him in suitable doses from the very first, and it was also 
used largely in washing and dressing wounds. All these, and many other attempts 
to improve the salubrity of his wards, unfortunately availed little or nothing. 


Cameron ends his description of the treatment of wounds at that time as 
follows :— 


When I first became a dresser, the carrying out of such details was 
my daily occupation. Every wound discharged pus freely, and putrefactive 
changes occurred in the discharges of all, producing in the atmosphere of every 
surgical ward, no matter how well ventilated, a fetid sickening odour, which 


INTRODUCTION XX1ll 


tried the student on his first introduction to surgical work just as much as the 
unaccustomed sights of the operating theatre. It is hardly necessary to add 
that fatal wound diseases and complications were never absent at anv time 
from the hospitals of that day. 


Such then was the state of surgical practice about the time when Lister 
began his work. From his student days, the subjects which had most attracted 
his attention were inflammation and the general septic diseases which so con- 
stantly followed the infliction of wounds, and when he commenced surgical 
teaching in Edinburgh the nature of inflammation occupied a very prominent 
place in his lectures as in his thoughts. Being dissatisfied with the views held at 
that time, he proceeded to investigate the subject for himself, and produced his 
classical papers on the early stages of inflammation, on the pigment cells of the 
frog, and on the nervous regulation of the arteries ; subsequently, as has been 
mentioned above, his attention was turned to the subject of coagulation of 
the blood, and to the behaviour of blood in healthy and diseased blood-vessels. 
But although these investigations furnished most important results and were of 
inestimable value in his subsequent work, yet they did not directly lead him to 
the antiseptic principle in surgery. 

In spite of the ight thrown on inflammatory processes by his researches, 
there still remained the fact that inflammation and suppuration constantly 
occurred after the infliction of open wounds, and that the various septic diseases 
frequently attacked the simplest wounds and rendered the most skilful operations 
unavailing. Most surgeons had become resigned to the occurrence of inflamma- 
tion and suppuration in wounds, and looked on them as natural and inevitable 
consequences. Many indeed regarded the occurrence of ‘ healthy ’ suppuration as 
a thing to be desired, because it was observed that once suppuration was 
established the patient’s condition improved. It was therefore assumed that 
the sooner suppuration occurred the better. Hence the aim of many was to 
hasten the formation of this ‘laudable’ pus, and at the same time to control 
‘the excessive action’ in the wound which was supposed to lead to the various 
septic diseases. 

This was not Lister’s view. His ideal of what should happen in a wound 
was what occurred in a subcutaneous injury such as a simple fracture, in 
which repair took place without any inflammation, suppuration, constitutional 
disease, or general sepsis. In his opinion the occurrence of inflammation and 
suppuration in a wound was by no means a desirable thing, but was, in fact, 
contrary to the natural processes, as exemplified by subcutaneous injuries, and 
was therefore to be avoided rather than aimed at. 

At an early period Lister had come to recognise that the essential cause 


XX1V INTRODUCTION 


of the troubles after operations and injuries was in some way or other con- 
nected with the putrefaction of the blood and discharges in wounds. Putre- 
faction did not occur in subcutaneous injuries, or in wounds which healed by 
first intention, and in these there were no septic troubles, while conversely, as 
soon as putrefaction appeared, inflammation and other septic diseases followed. 
He concluded, therefore, that these complications were due to the formation of 
irritating materials in the discharges of the wounds as the result of putre- 
factive fermentation, and that the aim of treatment should be to get rid of the 
putrefactive process. 

In his Huxley Lecture? he refers to the treatment of hospital gangrene while 
he was house surgeon to Mr. Erichsen, and it is clear that even then he looked 
on the various diseases of wounds as essentially the result of putrefaction of the 
discharges. At that time the general teaching was that these putrefactive 
changes were the result of the action of the air, and more especially of the oxygen, 
on the organic fluids present in the wounds. He was never satisfied with this 
explanation ; like John Hunter, he was at an early period puzzled by a case of 
general surgical emphysema after fracture of the ribs with puncture of the lungs, 
for although air was present in the tissues and in contact with a large amount 
of blood, putrefaction and septic troubles nevertheless did not occur. This 
puzzle was constantly present in his mind until the solution was revealed by 
the researches of Pasteur. 

It is interesting to note in passing that even after the introduction of anti- 
septic surgery, some surgeons, unwilling to give up the oxygen theory, spoke of 
the antiseptic dressings as ‘occlusive’, their assumption being that the dressings 
excluded oxygen. Lister himself always recognised the hopelessness of any attempt 
to exclude oxygen, and never made any efforts in that direction. He had already, 
as has been pointed out, tried to mitigate the putrefactive process by scrupulous 
cleanliness, insisting on the washing of the hands between the dressings, a plenti- 
ful supply of towels in the wards, and the use of various substances which we 
now know to possess antiseptic properties. No appreciable improvement resulted, 
and it was perhaps fortunate for the development of antiseptic surgery that 
Lister’s wards were so insanitary that these attempts at cleanliness were of little 
avail. It is important to remember this fact, for the considerable improvement 
which in numerous instances followed on the recognition of the great importance 
of scrupulous cleanliness, led many surgeons to attribute the good results of 
antiseptic surgery entirely to simple cleanliness and not to the destruction of 
bacteria. 

At this time (the early ‘ sixties’ of the last century) Lister, then Professor 


** Vol. ti, p. 515. 


INTRODUCTION XXV 


of Surgery in the University of Glasgow, was constantly speculating on these 
matters, especially on the cause of the putrefaction of the discharges in 
wounds, and during one of his discussions with friends the suggestion was made 
that the perusal of Pasteur’s papers on fermentation and spontaneous generation, 
which had then recently appeared, might be of assistance to him. This sugges- 
tion was fertile, and it may well be imagined how great a revelation to Lister 
were these researches of Pasteur. The oxygen theory of putrefaction, which had 
- seemed to oppose all advance, was at once swept away, and the problem was now 
seen to be not to exclude intangible gases, but to deal with living organic particles 
which could be destroyed and the characteristics of which could be carefully 
studied. . 

It is interesting to note that previous to the appearance of Pasteur’s work 
three papers had been published which really laid the foundation of the germ 
theory and of modern bacteriology ; these were by Schultze in 1836, Schwann in 
1837, and Cagniard-Latour in 1838. The two latter authors brought forward 
a large amount of evidence which satisfied them that the alcoholic fermen- 
tation of grape-juice was due not to oxygen but to the growth in the fluid of the 
Torula cerevisiae. Schwann also studied the putrefactive decomposition of meat- 
juice and other organic substances, and came to the conclusion that it was not the 
gases of the air which caused these changes, but organic particles which floated in 
the air, and could be destroyed by heat. He went further and ascribed all fer- 
mentative processes to the growth of the organisms found in fermenting liquids. 
In 1854 additional evidence was brought forward by Schréder and Dusch, who 
showed that it was not necessary, following the example of previous observers, 
to calcine the air which had access to the flasks, but that putrefaction did not 
occur in organic fluids contained in flasks if the air entering the flasks were 
filtered through cotton-wool. Pasteur finally (1864) completed the proof by 
showing that it was not necessary either to heat the air or to filter it before 
admitting it to properly prepared organic fluids, but that if it were con- 
ducted along a tortuous tube in which the dust could settle before it reached 
the fluid, no change took place in the organic matter. He showed also that if 
flasks containing putrefactive material were left open in a place where the air 
had been undisturbed sufficiently long to allow the dust to settle, as, for example, 
in a cellar, no decomposition took place, nor did any micro-organisms appear in 
the fluids. 

Apart from these researches on the causes of fermentation, much heated 
discussion had gone on for many years as to the significance of the minute 
“animalculae ’ which appeared in decomposing fluids, and the question whether 
these organisms originated de novo from the organic fluids in which they were 


XXV1 INTRODUCTION 


found, or whether they always came from pre-existing organisms which had 
somehow or other gained admission to the fluids, had been warmly debated. 
Pasteur’s work, however, really struck the final blow at the doctrine of 
spontaneous generation, although many further convincing proofs were 
brought forward later by other experimenters, notably by Tyndall and by 
Lister himself. 

The information, then, which Lister obtained from studying Pasteur’s work 
was (1) that organic fluids which had been boiled but were still prone to the, 
development of organisms and to fermentative changes, could be preserved 
without any change if the air admitted to the material after boiling had been 
calcined, or filtered, or had been kept at rest so long, or reached the fluids so 
slowly, that all the dust had had time to settle; (2) that the organisms found 
in the decomposing fluids were not produced spontaneously by changes in 
albuminoid materials, for they might appear and grow in artificial fluids con- 
taining mineral substances only ; (3) that these organisms were present in the 
dust of the atmosphere, and in that deposited on surrounding objects ; and 
(4) that the decomposition of the organic fluids coincided with the develop- 
ment of these organisms. If they were absent, no decomposition occurred ; 
as soon as they were admitted and began to grow, fermentative changes 
appeared. 

This was the work to which Lister’s attention was called, and it is easy 
to imagine the flood of light thrown on the whole subject of decomposition in 
wounds by its perusal. Lister at once applied himself to the task of finding some 
means of preventing the development of these living organisms in wounds. He 
formulated the hypothesis that the inflammation and septic diseases which 
occurred after wounds were due to the putrefaction of the discharges of the 
wounds ; while this putrefaction was in its turn due to the entrance of living 
micro-organisms from the air, and from the dust on surrounding objects. He 
made the deduction that if the access of living organisms could be prevented, and 
their growth in wounds arrested without at the same time damaging the wounds 
seriously by the means employed for this purpose, an open wound would follow 
the same course as a subcutaneous injury. No doubt this first conception was 
incomplete, but it was thoroughly sound, and while subsequent work has enor- 
mously extended the facts, the basal idea that it is the entrance of organisms 
into the wound from without which produces the inflammatory and septic 
troubles, and that therefore the aim of treatment must be to exclude or destroy 
them or inhibit their growth, still remains the fundamental principle of 
the treatment of wounds. The great variety of bacteria which may enter 
wounds, their very different behaviour, their various pathogenic properties, 


INTRODUCTION XXVI1I 


their origin, and the reaction of the tissues to their growth, are all subsequent 
developments which have had their influence on the details of the method, but 
which have in no way affected the original Listerian principle. 

With the light thus shed on the problems on which he had been pondering 
for years, Lister at once threw all his energies into the application to the treatment 
of wounds of the principle established by these researches in vitro. It was 
evident that filtration of the air which reached wounds was not a practical plan, 
nor could heat be used to destroy the organisms in all places from which they 
might contaminate the wounds, for these organisms were not merely floating 
in the air, but were deposited on all surrounding objects, and to operate in an 
atmosphere of filtered air, or of air previously subjected to heat, could not meet 
the requirements of the case. Hence he turned to the search for chemical sub- 
stances which possessed the power of destroying these living particles. About 
that time experiments had been made at Carlisle on the disinfection of sewage by 
German creosote, the active agent in which was crude carbolic acid; the interesting 
results so obtained suggested to Lister that this substance might serve his purpose, 
and he accordingly procured a supply. He determined to test the new principle 
first in the treatment of compound fractures, the results in these injuries being 
especially bad at that time in his wards. He had to wait some months before 
he could put his ideas into practice, but at length the opportunity came, and on 
the 12th of August, 1865, he was able to put the matter to the test, with results 
which amply justified his hypothesis. It is very curious that the material thus 
more or less accidentally selected in the first instance as an antiseptic has turned 
out to be the most suitable of any yet known and tested for various purposes 
in connexion with the asepsis of wounds, especially for the disinfection ot 
the skin. 

Now followed a period of the most remarkable activity, involving an amount 
of mental exertion and patient toil which probably no other man would have had 
the genius or indeed the physique to carry through. Lister came to this work 
equipped in an entirely exceptional manner. Endowed with extraordinary mental 
insight, and provided with much physiological and chemical knowledge, he had 
spent years in considering and investigating the subject of wounds, and he was thus 
able to grasp the significance of the numerous new phenomena which he observed 
while carrying out his methods of treatment. During this early period every case 
contributed fresh information, and led to constant improvement in his attempts 
to imitate nature’s processes, and this constant modification of his methods in 
accordance with fresh observations is remarkable evidence of his clearness of 
vision, and a striking proof of the elasticity of his mind and of the absence ot 
bias. To the very end of his active work as a surgeon he was never entirel\ 


XXV111 INTRODUCTION 


satisfied, but was always straining for something better, having ever in mind his 
one great ideal of making the conditions existing in an open identical with 
those in a subcutaneous wound. 

This activity took three great directions : (I) bacteriological work, especially 
in connexion with the germ theory of putrefaction ; (2) constant striving after 
improvements in the methods employed in carrying out the principle which he 
had laid down as essential in the treatment of wounds; and (3) improvements 
in the treatment of various diseases and injuries, rendered possible by the fact 
that operations had lost their greatest dangers. 


BACTERIOLOGICAL WORK 


In the early days Lister did a great deal of bacteriological work, partly 
in order to satisfy himself as to the accuracy of the theory on which he had 
based his system of treatment, and partly to test suggested alterations in his 
methods. Very little of this work has been published, indeed most of it was 
never intended for publication, but what he has written shows the impress of 
his genius. He repeated Pasteur’s experiments, especially that of the flask with 
the contorted neck, and he showed that the same results might be obtained by 
another method, namely by the use of glasses provided with loosely fitting glass 
covers." He also pointed out the importance of properly sterilizing by heat all 
vessels employed in these experiments, and he introduced the methods of dry 
sterilization which are still employed for this purpose.? He devised a flask for 
the storage of organic fluids and also methods of filling tubes and vessels from 
these flasks, which are most valuable when working with fluid media.® 

Perhaps his most important work in pure bacteriology was that on lactic 
fermentation. In that he obtained for the first time a pure cultivation of a 
single species of bacterium (Bacillus lactis), and he demonstrated that the 
lactic fermentation was due to the growth of this organism in milk. In this 
connexion he devised a plan of separating different kinds of bacteria from 
one another by repeated dilution which, though very laborious, remained 
practically the only satisfactory means of obtaining pure cultures till the 
introduction of Koch’s method of cultivation on solid media. 

Experiments were also made on the sterility of the natural fluids of the body, 
such as milk and urine, before they came into contact with the external air. 
A great deal of work was done in the way of testing new antiseptics and the 
value of different dressings, in fact almost every one of the later stages in his 
methods was tested in this way. Very interesting also is his work on the value of 


= Voli. p.. 270: “a Vola; (pez * Vol. ii, p. 55. 


INTRODUCTION XX1X 


the inhibitory action of antiseptics on the growth of bacteria, as distinguished 
from their destructive action.' 

Apart from these experiments 7 vitvo, it must be realized that the intro- 
duction of the antiseptic system was one vast experiment on the living body. 
Up to that time, with perhaps the exception of observations by Davaine upon 
anthrax, no work had been done which demonstrated any pathogenic action of 
bacteria. Indeed during the early development of antiseptic surgery the question 
of pathogenic bacteria, as we now know it, did not arise. In the first instance 
it was ‘putrefaction’ in the discharges of a wound which was attacked, and 
though this was looked on as due to the bacteria present in these discharges, no 
classification of these bacteria into species was thought of, and no differentiation 
into pathogenic and non-pathogenic organisms was made. It was simply a case 
of preventing the entrance of bacteria as a class into wounds and their develop. 
ment there. Very soon, however, we find Lister pointing out that there must be 
different species of bacteria, and that putrefaction was not the only injurious fer- 
mentation which might occur in wounds, for he noted that in some cases, although 
there was no odour in the discharges, suppuration nevertheless occurred; thus, 
in a footnote toa paper published in 1870? he says: ‘ This group (cases of putre- 
factive suppuration) ought to include the products of other ferments besides those 
of putrefaction, for I am satisfied that inodorous ferments sometimes occur in 
the animal fluids and produce salts which stimulate to suppuration ; also viruses 
inducing suppuration are very probably of the same essential nature (ferments), 
though some at least are odourless, as in the case of erysipelas.’ It is true that 
he attributed the odourless suppuration in some of these cases to reflex distur- 
bance of the nervous system, produced, for example, by tension in the wound, vet 
at the same time he recognised that, in some instances at any rate, it was due to 
bacterial infection. Indeed it was more especially with the view of demonstrating 
that there are different kinds of bacteria, each with its own fermentative action, 
that he undertook his work on lactic fermentation. Very soon also we find him 
beginning to realize the possibility of the penetration of bacteria into the bod 
from the wound, and thus the distinction between pathogenic and non- 
pathogenic bacteria. 

Under the system he evolved not only did inflammation and suppuration 
disappear, but also pyaemia, hospital gangrene, erysipelas, and tetanus. In his 
demonstrations at the hospital he was fond of pointing out how erysipelas spread 
like fairy rings, as if the organisms which produce it were advancing in the tissues 
before the redness and dying out behind it, a view strikingly confirmed sub- 
sequently by Koch and others. He also remarked, with some diffidence it is true, 


A Wolrt. pe 273: * Vol. il, p. 140. 


xx INTRODUCTION 


on the disappearance of tetanus from his wards, as if that also were a disease 
due to bacteria. 

Another subject on which he soon began to speculate was the protective 
arrangements of the body. He succeeded in preserving urine and milk from 
alteration without subjecting them to any preliminary treatment by boiling or 
otherwise, thus showing that bacteria did not penetrate. along healthy canals, 
such as milk-ducts. This he attributed to the destructive action of the healthy 
living organism on the bacteria, and he pointed out that in wounds also it was 
capable, to a certain extent, of disposing of micro-organisms. Although Lister 
did not do any experimental bacteriological work on animals, there is no doubt 
that the remarkable results obtained by his methods of wound treatment, and 
the energy and insight with which he laid stress on bacteria as the cause of the 
grave troubles following wounds, had a most important influence on others, 
leading them to the study of the pathogenic effects of bacteria, and thus served 
to stimulate the rapid development of the science of bacteriology. 


THE DEVELOPMENT OF THE ANTISEPTIC SYStEi- 


We have already traced matters up to Lister’s first application of his views 
to a case of compound fracture. That compound fractures should have been the 
form of injury selected by Lister as likely to afford the most suitable test of his 
hypothesis is not difficult to understand when it is remembered how great was 
the contrast in those days between the course followed respectively by simple 
and compound fractures. The latter were indeed the most fatal of all surgical 
injuries, and accounted for a large proportion of the cases of pyaemia which 
were of such frequent occurrence in all hospitals. 

The object aimed at being the prevention of the putrefaction in the wound 
brought about by organisms introduced either at the time of the accident or 
subsequently during the course of the treatment, means were taken to obviate 
both dangers. The first indication was fulfilled by introducing into the wound 
a pledget of calico or lint held in a pair of forceps and saturated with undiluted 
crude carbolic acid; with this all the interstices of the wound were thoroughly 
swabbed out. The second indication was met by placing over the wound, and over- 
lapping it in all directions, for about half an inch, a double layer of lint saturated 
in the same material. This lint was covered bya piece of thin block-tin or sheet- 


* In this section the history of the evolution of wound treatment which Sir Hector Cameron has given 
in his James Watson Lectures before the Faculty of Physicians and Surgeons of Glasgow has been largely 
drawn upon, and to that volume readers who desire a fuller guide to Part III of these collected papers 
are referred (Lord Lister and the Evolution of Wound Treatment during the last Forty Years. Glasgow. 
J. MacLehose & Sons. 1907. Post 8vo, pp. 96). See also vol ii. pp. 349, 365. 


INTRODUCTION XXX] 


lead, moulded in a concave form so as to fit over the mass of lint. It was fixed 
in position by strips of adhesive plaster, the limb being placed in suitable splints. 
The carbolic acid and blood mingling in the small piece of lint formed a thick 
paste, and converted the whole into a sort of crust or scab, which adhered to the 
wound with great tenacity. Once a day the tin cap was removed, and the crust 
of lint and blood was painted over lightly on its outer surface with carbolic acid. 
What was aimed at was to keep this crust from becoming septic, while its under 
surface in contact with the wound, becoming gradually free from the carbolic acid 
which it at first contained, should cease to be irritating in itself, and therefore no 
longer interfere with the process of healing. The dressing was of the nature of an 
artificial scab, but with this difference, that the substance of the scab was charged 
- with an antiseptic introduced with the object of destroying any germs of putre- 
faction which might find their way to the scab from the skin, or from the splints 
padded with soft absorbent material to receive such bloody discharges as oozed 
from the wound during the first day or two. It was, however, recognised that 
the vapour of the carbolic acid retained under the cap of tin interfered with the 
process of cicatrization, and therefore, after it seemed likely that the wound was 
so far repaired as no longer to communicate with the seat of fracture, the anti- 
septic crust was detached, and the final closure of the surface wound allowed to 
take place under some simple form of dressing. 

The results of the application of the principle to the treatment of compound 
fractures could not have been more striking, for the patients suffered neither 
from putrefaction and inflammation in the wound nor from general septic 
diseases. The necessity for primary amputation in the majority of cases dis- 
appeared, many limbs and lives were saved, and the treatment of these injuries 
underwent a radical change. 

There is no instance in the history of surgery, and indeed few in the history 
of science, in which a deduction has been so completely verified when put to 
the test. 

Its success in this particular class of cases naturally suggested and even 
urged the extension of the principle to others, and it was not long before an oppor- 
tunity occurred of employing it in a case of psoas abscess, an affection from which 
at that period few adults recovered, while it was only slightly less fatal in 
children. The patient was a middle-aged woman, and the abscess, which was 
pointing in one loin, was about to burst. It was incised, and some of its thick 
contents mixed with the crude carbolic acid; two pieces of lint soaked in this 
mixture were laid over and around the wound and covered with a cap of block- 
tin. When the dressing was removed next day, there was no escape of pus as 
was usual under the treatment then customary, and pressure caused only a drop 


XXXIl INTRODUCTION 


or two of serous fluid to exude. This result, though highly satisfactory, produced 
a momentary embarrassment, for there was no pus or blood with which to mix 
the carbolic acid for the new dressing. This difficulty was overcome by thickening 
a solution of carbolic acid in boiled linseed oil (1 in 4) with whitening (carbonate 
of lime). This putty-like material was spread upon a piece of block-tin and laid 
over the incision, care being taken that this dressing overlapped it widely in all 
directions ; it was fixed in position by strips of adhesive plaster, and an absorbent 
compress was bandaged over all. The dressing was renewed daily. The result 
was entirely satisfactory; the abscess cavity remained free from any septic 
change, and eventually healed, having yielded no pus from first to last, but only 
a steadily diminishing quantity of clear serous fluid. 

This case taught many important lessons ; it not only afforded a fresh proof, 
under slightly different conditions, of the truth of the theory, but was the first 
demonstration of facts since grown familiar, but which could not then certainly 
have been foretold. These were that after the original contents of an abscess, 
whether acute or chronic, were evacuated, if changes in its interior resulting from 
contact with outside morbid agents be avoided, instead of pus onlya thin serous 
fluid would be discharged and would rapidly diminish in quantity; that in 
consequence it was neither essential to open the abscess at a dependent part, 
nor necessary to make counter-openings ; that under such circumstances no 
constitutional disturbance need be feared; and lastly, that such abscesses, if 
a careful course of antiseptic treatment were persevered in, might be expected 
to close permanently. 

A purer specimen of carbolic acid was obtained before long and found to 
be soluble in water in the ratio of one part in twenty (five per cent.). After the 
introduction of this carbolic lotion the method followed in the treatment of 
compound fracture was first to wash out the interior of the wound thoroughly 
with a five per cent. solution of the acid, and then to cover its surface with a piece 
of lint saturated with carbolic oil (zr to 4) large enough to overlap it in every 
direction ; over this was put a large dressing of the putty, smoothly spread on 
calico to the thickness of about a quarter of aninch. At first, a further covering 
of block-tin was employed, but its use was afterwards dispensed with as un- 
necessary. The dressing of putty was changed daily, but the piece of oiled lint, 
soon saturated with blood, was left next the wound, harbouring under it a crust of 
blood of greater or less thickness. It became usually fairly dry, and when the time 
arrived for removing the crust and discontinuing the splints, either a firm cicatrix 
or a superficial granulating sore was exposed to view. In opening an abscess 
a large piece of lint soaked in a solution of carbolic acid (r to 4) was placed over 
the portion of the skin to be incised and left for a little to act upon it. The lower 


INTRODUCTION XXXlil 


edge of it was then raised, the incision made, and the curtain of lint let fall, the 
abscess being evacuated by gentle pressure under its protection. The anti- 
septic was not injected into the cavity of the abscess, experience having shown 
that while such injection was quite superfluous, it could only do mischief by 
causing irritation. A narrow strip of lint dipped in the same oily solution 
was introduced through the incision to prevent primary union and at the 
same time to act as a drain. On removal of the oily antiseptic curtain a 
dressing of the putty, spread on a piece of block-tin, was immediately fixed 
over the incision by adhesive plaster and bandaged to the part. The thin 
discharge flowed out beneath the edges of the putty, which was renewed 
yonce. a. day. 

The use of block-tin was not long continued: the putty was spread upon 
calico, and in this form the dressing was extended to the treatment of incised 
wounds made by the surgeon. Although the results obtained with this anti- 
septic putty dressing were strikingly satisfactory, its employment was attended by 
certain practical inconveniences, and Lister devoted a great deal of patient 
research to devising a substitute which should be not less effective to achieve 
the main object in view, but more convenient in use. After many experiments, 
he found a suitable material in shellac prepared in the following manner. When 
mixed with carbolic acid (rz to 4) shellac forms a flexible mass from which, 
as from a reservoir, the acid is constantly and not too rapidly given off. The 
practical objection to its use in this form was that it adhered too firmly to the 
skin, but this was overcome by spreading the mixture on calico and then painting 
a solution of india-rubber in benzene over thesurface. The thin layer of india- 
rubber left on the surface of the shellac when the benzene evaporated prevented 
the plaster sticking to the skin, while the carbolic acid as it was liberated from 
the shellac passed freely through it. This new dressing presented many practical 
advantages. It was not disintegrated by friction like putty, and being much 
lighter was not only far less cumbrous, but could be more easily maintained 
in position ; while, further, it was always ready for use, whereas the putty had to 
be specially prepared by the surgeon on each occasion. It was adopted alike for 
the treatment of injuries, abscesses, and incised wounds. In the last the method 
of treatment was as follows : During the performance of an operation the wound 
was from time to time irrigated with carbolic lotion, and more especially was 
filled with this lotion while it was being stitched up. The lotion was then 
expressed from the wound, the lac-plaster immediately applied, overlapping the 
surface to a considerable area around the wound, cloths being placed about the 
margin in order to absorb the discharge that passed out from under the lac-plaste! 
Attention was also paid to the drainage of wounds, and for this purpose a strip 


LISTER I G 


XXXIV INTRODUCTION 


of lint soaked in a solution of carbolic acid and oil (r to 4) was inserted at one 
angle of the wound and retained for at least forty-eight hours. 

It will be observed that these early antiseptic dressings were not absorbent, 
and were therefore impervious to the discharges from the wound. Though the 
carbolic acid they contained could not be washed out of them, however great the 
flow of blood or serum in the early stage, it was constantly given off, thus pre- 
venting the entry of infective organisms. The fluids of the wound were, alike 
by the putty and the lac-plaster, shed from it in an antiseptic atmosphere main- 
tained between the dressing and the skin by the carbolic acid slowly and con- 
stantly liberated from the putty or lac. Under the lac-plaster the wound healed 
without a scab. 

The favourable reports of some surgeons on the use as an antiseptic dressing 
of oakum carefully selected and teased into a fine soft uniform mass next induced 
Lister to consider the advantages of a dressing which would absorb the fluids 
of a wound instead of distributing them. His previous objection to the use 
of porous dressings was founded on the observation? that the discharge, if at all 
free, washed out the antiseptic from the fibres of the material used and, by 
leaving over the wound a dressing devoid of any antiseptic, opened up the way 
for the penetration of putrefaction. In oakum, however, each fibre was imbued 
with the antiseptic (creosote) in an insoluble vehicle, so that the discharge could 
not wash the antiseptic out of the fibres any more than in flowing beneath the 
lac-plaster, to a narrow strip of which each individual oakum fibre might fairly 
be compared. 

While impressed with the advantages of an absorbent material thus thoroughly 
imbued with an antiseptic which would not be washed out of its fibres by the 
discharges, Lister preferred to devise a dressing in which the proportion of the 
antiseptic could be accurately adjusted, and free from certain minor practical 
drawbacks which attended the use of oakum. This led to the introduction 
of the gauze dressing, which in one form or another has since been and still is 
used all the world over, either charged with some antiseptic substance or sterilized 
by heat. Acheap muslin of open texture, known in the trade as ‘book-muslin ’, 
was charged with resin, paraffin, and carbolic acid. Resin, which is one of the 
principal constituents of ordinary oakum, holds carbolic acid with great tenacity, 
so that a mixture of one part to five does not, if applied to the tongue, produce 
any undue sense of pungency. The paraffin was added to obviate the objection 
that this mixture was very sticky, as well as apt to be irritating to many skins. 
The melted ingredients were mixed in the proportion of one part of the acid 
to four respectively of resin and paraffin, and the mixture was diffused through 


1 Vol. ii, p. 168. 


INTRODUCTION 


XXXV 

the fibres of the cloth. This antiseptic gauze had carbolic acid thus fixed in every 
fibre, while the fine spaces between, which give its porous character to the cloth. 
were still open for the discharge to pass through. It was folded in such a way 
as to make a thickness of eight plies and placed over the wound, overlapping it 
widely in all directions. But in order to prevent fluids from solng straight 
through the eight plies of gauze and possibly exhausting its antiseptic ingredients 
at that part, a piece of very thin macintosh or jaconet, previously washed in the 
antiseptic lotion, was incorporated with the mass of gauze by being slipped 
under its top layer, thus leaving seven layers of the gauze next the wound, and 
compelling the discharges to make their way to the margins of the dressing, 
instead of coming straight through. 

As has already been said, the whole aim of Lister’s work was to bring about 
and maintain in an open wound conditions similar to those which exist in a 
subcutaneous injury, and from the first he fully recognised that while fermentative 
changes were the most important they were not the only sources of irritation— 
that in fact the chemical substance employed to prevent fermentation was also 
more or less irritating, and interfered with the attainment of his ideal. He there- 
fore now directed his attention to devising means of diminishing or altogether 
avoiding irritation of the wound by the carbolic acid contained in the dressings. 
The irritation produced by the antiseptic which came into contact with the wound 
during the operation was only temporary. The carbolic acid when mixed with 
the blood lost much of its irritating character, and was moreover absorbed, 
and disappeared from the wound in a comparatively short time. When once 
the wound had been closed at the operation, Lister considered it unnecessary 
to irritate the line of incision or the interior of the wound by subsequent appli- 
cations of the antiseptic. He therefore never syringed out a wound at a subse- 
quent dressing, as some surgeons were fond of doing; the utmost he did was to 
have some carbolic lotion flowing over the line of incision and the adjacent skin 
while the dressings were being changed. This lotion did not penetrate into the 
interior of the wound, and acted on the surface only for the brief period during 
which it was exposed. Nevertheless he recognised that the carbolic-acid vapour 
coming off from the gauze or the lac-plaster was irritating to the line of incision, 
and therefore he made numerous experiments with the view of finding some 
material more or less impenetrable to the vapour of carbolic acid, which might 
be placed directly over the wound below the carbolic gauze, but widely ove! 
lapped by the absorbent antiseptic gauze dressing. Though the vapour o! 
carbolic acid passed easily through gutta-percha tissue and thin sheets o! india- 
rubber, the common oil-silk used for covering water dressings was found to b 
much less penetrable by it. Taking this as a basis, he covered it with 


Cc ? 


XXXVI INTRODUCTION 


copal, which was found to offer even stronger opposition to the passage of 
carbolic acid than oiled silk itself, and lastly, painted over both a solution 
of dextrine, which permitted the surface to be uniformly wetted. Before 
being applied to the wound this ‘protective plaster’ was dipped in a 
solution of carbolic acid. The acid was soon dissipated, and the plaster 
became an unstimulating covering to the wound, defending and _ protect- 
ing it from the direct action of the superimposed and widely overlapping 
antiseptic dressing, but in no way interfering with the outflow of the blood 
and serum. 

While these improvements in the material of the dressings and their manner 
of application were in progress, another question had been engaging Lister’s 
attention, and had been the subject of much thought and experimental inquiry. 
From an early stage he had seen that if the full advantages of the antiseptic 
system and all that it implied were to be realized in general surgical treatment, 
the method of arresting haemorrhage, and especially the kind of ligature used, 
must be reconsidered. He had very early obtained evidence that blood-clot 
could, in the absence of fermentative changes, undergo organization. In 1867+ 
he placed on record the following observation: ‘I was detaching a portion of 
the adherent crust from the surface of the vascular structure into which the 
extravasated blood beneath had been converted by the process of organization, 
when I exposed a little spherical cavity about as big as a pea, containing brown 
serum, forming a sort of pocket in the living tissues, which, when scraped with 
the edge of a knife, bled even at the very margin of the cavity. This appearance 
showed that the deeper portions of the crust itself had been converted into living 
tissue. For cavities formed during the process of aggregation, like those with clear 
liquid contents in a Gruyére cheese, occur in the grumous mass which results 
from the action of carbolic acid upon blood; and that which I had exposed had 
evidently been one of these, though its walls were now alive and vascular. Thus 
the blood which had been acted upon by carbolic acid, though greatly altered 
in physical characters, and doubtless chemically also, had not been rendered 
unsuitable for serving as pabulum for the growing elements of new tissue in its 
vicinity.’ He also made an observation which was quite novel at the time, that 
a piece of dead bone which lay exposed in the wound of a compound fracture, 
instead of being exfoliated as would have occurred in a septic wound, became 
absorbed.’ 

These and other similar observations raised the question whether ligatures 
might not be cut short and left in the wound, for it seemed reasonable to hope 
that, just as dead bits of tissue had been disposed of by absorption, so more or 


“Vol, i, p. 'S. e Vols p: 0: 


INTRODUCTION 


XXXVI1I 
less slender threads of organic material, prepared so as to be free from septic 
organisms, might be similarly removed. 

Lister’s experiments and observations on this subject are fully recorded in 
papers printed in volume ii. He first, on the 12th of December, 1867, tied 
the left carotid artery of a horse with purse-silk which had been steeped in a 
strong watery solution of carbolic acid ;' the ends were cut short, and the wound, 
which was dressed antiseptically, healed immediately. Six weeks later the horse 
died, and on laying open the vessel there was found at the cardiac side of the 
ligature a firm adherent clot, an inch and a quarter long, but at the distal side 
coagulation had been entirely prevented by the reflux current of blood through 
a branch about as large as the human vertebral artery, which took origin as close 
to the ligature as possible. Under such circumstances secondary haemorrhage 
would certainly have occurred had a thread been applied in the manner then 
commonly employed. But in this specimen the artery appeared as strong at 
the part tied as elsewhere. The cul-de-sac showed some irregularity due to 
puckering of the internal and middle coats, but the surface appeared completely 
cicatrized, and presented the same character as the natural lining membrane 
of the vessel, and the ligature, which seemed as yet unaltered, was found lying 
dry in a bed of firm tissue. The tissue within the noose was apparently a new 
formation in place of the portion of external coat killed by the tightly tied 
thread ; externally, the constriction, necessarily caused in the first instance by 
tying the ligature, had been filled in by a similar compact structure. 

The success of this experiment justified the application to man of the 
principle upon which it was based. Accordingly, when a few weeks later (29th of 
January, 1868) Lister was called upon to tie the external iliac artery for aneurysm 
of the common femoral artery in an elderly lady, he made use of a silk ligature 
steeped in undiluted carbolic acid, used sufficient force to divide the inteinal 
and middle coats of the artery, cut the ends of the ligature short, and dressed 
the wound antiseptically. The aneurysm consolidated, the wound healed without 
suppuration, and the patient was out of bed in four weeks, and was able to take 
outdoor exercise in two more. Within a year she died suddenly from rupture 
of an aortic aneurysm. Careful examination of the iliac artery after death 
showed that the knot of silk was still in great part present, enclosed in a thin- 
walled capsule. Besides the remnant of the ligature, the tiny capsule contained 
a minute quantity of yellowish semi-fluid material, looking to the naked eye 
very like thick pus. Microscopic exaniination, however, proved that pus cor- 
puscles formed but a small proportion of its constituents, which were princi- 
pally rounded corpuscles of smaller size, and fibro-plastic corpuscles, together 


* Vol. i, p. 64. 


XXXVI INTRODUCTION 


with some imperfect fibres and granular material. There were evidences of the 
silk having been eroded by the action of the tissues around it, pieces of its fibres 
being present in the puriform fluid ; they had not been materially softened, but 
only ‘ superficially nibbled, so to speak. Indeed,’ Lister added, ‘ considering the 
organic character of silk, the remarkable thing seems to be, not that it should be 
absorbed by the living tissues, but that it should resist their influence so long.’ 

The local result in this case was thus not altogether satisfactory, and Lister 
therefore turned his attention to other materials. Animal ligatures of various 
kinds, catgut, tendon, and leather, had long before been tried and abandoned 
as unsatisfactory, but there was good reason to expect that in the absence of 
sepsis very different results would ensue. Lister had been struck by the fact 
that the sloughs and clots produced by the injection into naevi of strong solutions 
of perchloride of iron or tannic acid, though impregnated with these substances, 
yet rapidly disappeared without suppuration. He had also learnt that portions 
of dead tissue and of blood-clot, free from sepsis, were absorbed, and that this 
process was in no way interfered with when carbolic acid had freely acted upon 
them. There seemed, therefore, to be no reason why carbolic acid should not 
be used for disinfecting the animal ligature. 

In his next experiment, in which (on the 31st of December, 1868) he tied 
the right carotid of a calf at about the middle of the neck, he applied two ligatures 
separated from each other by a distance of about an inch and a half. One was 
composed of three strips of peritoneum from the small intestine of an ox, twisted 
into a cord, the other was of fine catgut. Both had previously been soaked for 
four hours in a saturated watery solution of carbolic acid. The wound healed by 
first intention, and the calf was killed a month afterwards. The result of the 
dissection of the vessel was at first disappointing, for the ligatures were still to 
all appearance present and as large as ever ; more minute examination showed 
that in reality they had been absorbed and replaced by bands of living tissue, 
‘the growing elements of which had replaced the materials absorbed, so as to 
constitute a living solid of the same form’. The fleshy bands so formed were 
continuous with the arterial walls, and so far from weakening the vessel at the 
point of ligature had rather strengthened and reinforced it, while by the early 
healing of the wound an immediate reconsolidation of the tissues detached from 
the vessel had taken place. The evidence of the organization of the ligatures, 
clear to the naked eye, was abundantly confirmed by the microscope. All these 
facts seemed to give sure promise, as indeed has proved to be the case, of security 
against secondary haemorrhage, so frequent and so justly dreaded up to that 
time, as well as of the absence of suppuration in connexion with such 
ligatures. 


INTRODUCTION XXX1X 


Lister subsequently gave much time and thought to the discovery of the best 
methods of preparing the catgut ligature so as to meet the various conditions 
which were required, and his latest contribution to the subject was in fact pub- 
lished so recently as the 18th of January, 1908.1 The raw catgut as obtained 
from the shops was unsatisfactory, for the ligature as soon as it becarne soaked 
with fluid, and especially with serum, swelled up, and the knots became untied : 
further, it was absorbed too rapidly, a most serious drawback. The chief points 
to which he paid attention in the preparation of catgut suitable for general 
surgical use were the breaking strain, the solidity and permanence of the knot, 
the pliability of the material, and the rapidity of its absorption in the tissues ; 
the papers in which he described the different methods devised for attaining 
these objects are reprinted in the second volume. At the present time, in the 
preparation of catgut attention is directed chiefly to its sterilization, without 
special reference to the other essentials on which so much stress was laid by 
Lister, but it may be doubted whether this is wise, and whether any better 
material than Lister’s sulpho-chromic catgut has been introduced. 

The adoption of absorbent dressings and absorbable ligatures marked a 
distinct stage in the development of antiseptic surgery ; by simplifying the 
technique and rendering the results surer in the hands of other surgeons, it 
greatly contributed to bring about the general adoption of the system, and 
paved the way for the extraordinary extension of the field of surgery which the 
next quarter of a century was to witness. 

At about the same time the metallic suture ceased to be the sole method 
of closing the wound, giving place to more convenient stitches of silk. In 1870° 
Lister gave an interesting account of the methods he employed in stitching up 
a wound, especially in those cases in which a portion of the skin had been removed, 
and where, therefore, there was considerable tension at the edges of the wound. 
The silk was rendered aseptic by being impregnated with a mixture of carbolic 
acid and melted bees-wax, and was kept in a five per cent. solution of carbolic 
acid until required. Catgut was also used in suitable cases for stitches, silver 
wire was employed where much tension existed, and silkworm gut and horsehair 
were utilized especially in septic cases. Later, waxed silk was replaced for 
most purposes by ordinary Chinese twist, rendered aseptic by having been steeped 
in I to 20 watery solution of carbolic acid. 

It was at about this period also that Lister began to make use of the india- 
rubber drainage-tubes devised by Chassaignac early in the century for carrying 
off pus. Though no pus was formed in aseptic wounds, yet a considerable flow of 
blood and serum followed immediately upon the infliction of the wound, however 


1- Vol. 0, p. 119. * Vol. i p. 139. 


x] INTRODUCTION 


managed. Pressure forceps, the use of which makes it possible to stanch by 
a few minutes’ pressure, and, if thought necessary, to tie all bleeding-points, had 
not yet been introduced. Moreover, the stimulation of the wound by the anti- 
septic fluid, even though the endeavour was made to reduce this to a minimum, 
increased the flow of serum. To prevent the accumulation of these discharges, 
Lister had been in the habit of introducing and retaining for at least forty-eight 
hours, at one angle of the wound, a strip of lint soaked in a solution of carbolic 
acid and oil (1 to 4). The substitution of india-rubber drainage-tubes proved 
a valuable improvement in antiseptic technique. They were, of course, kept 
constantly immersed before use in a strong solution of carbolic acid. 

Holding the view that the dust floating in the air was a potent source of 
infection, but recognising that the contact of carbolic lotion with the wound 
during the operation and at subsequent dressings was a source of irritation, Lister 
at about this period introduced the use of a spray of carbolic acid solution to play 
around the wound, with the view of destroying the germs floating in the air before 
they settled on the wound. He, however, eventually convinced himself, firstly; 
that the spray did not thoroughly disinfect the atmospheric dust, and secondly, 
that not only were the microbes in the air for the most part not pathogenic, but 
also that the tissues were capable of destroying organisms, provided they were 
neither very numerous nor very virulent. After full consideration of all the 
facts, and especially those constantly observed in the treatment of empyema,} 
Lister abandoned the use of the spray without reverting to the other precautions 
against the atmospheric infection which had formerly been deemed, and perhaps 
then were, essential. 

Although carbolic acid had proved so conspicuously satisfactory as an 
antiseptic for use in surgery, it was open to two objections. The first was that 
it was irritating to the wound, and must therefore to some extent retard healing, 
and was poisonous if absorbed in quantity; the second, that, being volatile, 
it was constantly being dissipated from the dressings, which it was therefore 
deemed advisable to change oftener than would otherwise have been necessary. 
Lister, consequently, was always seeking to find some substance which, while 
possessing adequate antiseptic properties, would yet be unirritating, non- 
poisonous, and non-volatile. 

Among a large number of substances which were tested in practice, the 
tollowing may be mentioned. In consequence of reports as to the value of 
boracic acid for the preservation of food, this substance was very extensively 
tried ; it was, however, found to be quite inefficient as an antiseptic for ordinary 
practice, but it did very well in the case of superficial sores and ulcers, and for 


’ Address to International Medical Congress, Berlin, 1890. Reprinted in vol. li, p. 332. 


INTRODUCTION 


xhi 
those purposes it has continued to be used. At the present time, under suit- 
able circumstances, boracic lotion (saturated solution of boracic acid in water). 
boracic lint, and boracic ointment are commonly employed. Salicylic acid was 
much praised by Thiersch, and was consequently carefully tested by Lister, but 
it was found to be open to many objections, especially that it was irritating to 
the wounds, and inefficient as an antiseptic. It is only used now in the form 
of salicylic wool and salicylic ointment. Thymol was for a time a favourite anti- 
“septic with some surgeons, but after testing it in various ways it was rejected 
as being untrustworthy. Preparations of eucalyptus also failed to meet the 
requirements, and it only remains in use in the form of ointment, which is 
still occasionally employed, chiefly in the treatment of burns. Acetate of alumina 
was used to a considerable extent at one time, but on putting it to a careful test 
it also was rejected. | 

After the publication of Koch’s earlier papers on disinfection, the various 
mercurial salts were examined, and they form a very essential part of the anti- 
septic equipment at the present time. A good deal of time was expended in 
testing the relative merits of lotions of the biniodide and perchloride of mercury : 
the conclusion reached was that, from every point of view, especially in respect 
to its efficiency as an antiseptic and lesser tendency to irritate the skin and the 
wound, the perchloride was superior to the biniodide. The strength of the 
perchloride lotions employed at an early period, I-2000 and I-4000, were the 
strengths used by Lister at the end of his work, and are still extensively employed. 
A great deal of labour was also expended on finding a suitable mercurial dressing 
which should, on the one hand, be non-irritating to the skin, and on the other 
would provide a sufficient store of antiseptic to obviate the necessity of frequent 
changing of dressings, even when the discharge was considerable. The record 
of several of these attempts will be found in the published papers ; for example, 
we have! a description of an attempt to form a gauze with a combination of 
perchloride of mercury and albumen. This again, gave place* to a gauze 
containing the double chloride of mercury and ammonium (sal alembroth). 
Sal alembroth, however, had the defect of being very soluble in the serum of 
the discharges, and the solution so formed was very apt to irritate the skin ; it 
eventually gave place to the double cyanide of mercury and zinc, which was quite 
unirritating, and while sufficiently soluble in blood to give to the gauze charged 
with it sufficient antiseptic power to inhibit the growth of microbes, was yet 
not so soluble as to be washed out of the dressing by the discharges, however 
copious. An aniline dye added to the salt was found to have the double advan- 


} 


tage of fixing the double cyanide in the gauze, so that it did not shake out When 


*  Wolg.1y pp. 3038 2 Vol. ii, | 


xhi INTRODUCTION 


dry, and of indicating that the dressing had been uniformly charged. The use 
of this insoluble and non-volatile antiseptic allowed the macintosh covering to 
be dispensed with, and thus the discharges could dry up and the gauze became 
a dry dressing. In place of macintosh, a mass of antiseptic wool (double cyanide 
or salicylic) was applied outside, so as to add to the thickness of the antiseptic 
material through which the discharge had to pass. 

Lister, as Cameron has pointed out,’ was probably the first to use a dressing 
sterilized by heat, and not containing any antiseptic substance. This he did while 
still Professor in Edinburgh, and the material used for the purpose was absorbent 
cotton-wool. He did not, however, persevere in the practice, because he felt 
that it could only be safely adopted in such cases as furnished a comparatively 
small amount of discharge, for if the discharge came through the dressing without 
having acquired any antiseptic material in its passage, there was nothing to 
prevent putrefaction spreading into the wound. Hence in cases in which there 
was a considerable amount of discharge, it was necessary to change the dressings 
very frequently ; and further, the successful employment of sterilized materials 
not containing antiseptics was a much more difficult and complicated matter 
than the use of antiseptic dressings, and implied considerable practical experience 
in bacteriological work. He therefore preferred to retain the use of antiseptics 
judiciously chosen and carefully used, so that, while their germicidal influence 
was retained, an irritating effect was avoided. 

By the time he ceased active work as a surgeon, he had arrived at a method 
of wound treatment in which the maximum amount of protection against 
bacterial invasion was secured with a minimum amount of irritation to the wound. 
The result was that the frequent dressings formerly employed were given up, 
and usually one dressing, or at most two, sufficed for a clean case. At the same 
time also the irritation of the wound had been so much reduced that, in a great 
majority of cases, there was no necessity for drainage; in fact, his ideal of 
a subcutaneous injury had been more or less attained. 


GENERAL SURGICAL, ACTIVITY 


Apart from the surgical improvements directly resulting from the preven- 
tion of sepsis, Lister published various articles on other surgical subjects. 
Attention may especially be directed to the article on excision of the wrist, 
and to the essays on amputation and anaesthetics * written for Holmes’s System 
of Surgery. The article on amputation differs from other articles on the same 
subject written at that date, in that it presents the reader with the principles 


* loc. cit, Vols is sp. At, * Vok 4i;, px 375% Vole 15. ps 0356 


INTRODUCTION xi 


which should guide the surgeon in dealing with the several parts of each limb, 
and omits those tedious details which are often more confusing than instructive. 
One of the best amputations of the thigh is here described for the first time. 
The essay on anaesthetics set forth the methods then employed in Edinburgh, 
and supported them by scientific arguments in favour of their validity. The 
subject of anaesthetics was one in which Lister has always taken the keenest 
interest, and it is needless to add that his teaching has many followers at the 
present day. 

Another very interesting paper was that on the effects of the position of 
a part on the circulation through it.1. For years before the introduction of 
Esmarch’s bandage, Lister had been in the habit, in operations on the extremities, 
of elevating the limb for a few minutes, and then, while it was still elevated, 
applying a tourniquet at the upper part; in this way he brought about a blood- 
less state of the limb. On the publication of Esmarch’s paper, Lister adopted 
his elastic band in place of the tourniquet ; but he continued to employ elevation 
of the limb, as a safer means of emptying it of blood in the first instance than 
the application of a bandage from below upwards, as advised by Esmarch. In 
the paper to which reference is made Lister explained his views as to the mode 
in which his plan brought about the desired exsanguine state. 

As soon as it became evident that antiseptic methods protected the patient 
against septic diseases, a great change came over general surgical treatment, and 
from the very first there was not a case admitted into Lister’s wards which was 
not considered from a fresh point of view. The dangers arising from the risk of 
wound infection being averted, the question arose in most instances whether 
something better might not be done in the way of treatment by operation than 
had been customary. The result of the treatment of compound fractures by 
the antiseptic principle was that instead of looking on amputation of the limb 
aS an imperative procedure, in the great majority of cases that plan became 
relegated to a secondary place, and all the surgeon’s energies were devoted 
to an attempt to save the limb. The result is that nowadays amputation is 
only very rarely performed in compound fracture, or compound dislocation. 
The method led also to a complete revolution in the treatment of spinal abscess 
and tuberculous abscesses of joints generally. Quite early the subject of 
ununited fractures was taken up, and instead of employing apparatus or 
inefficient subcutaneous operations, the bones were boldly cut down upon and 
repaired in any way which seemed mechanically advisable. From that it was but 
a step to operations on recent fractures,—the patella, for example—to operations 
for malunited fractures, and to osteotomy for knock-knee and other deformities. 


> Vol; 15, ps 176: 


xliv INTRODUCTION 


Operations on healthy and diseased joints were introduced—the bold removal 
of loose bodies from joints, drainage of chronic synovitis, incision into 
diseased joints, and so on. Extensive operations for cancer of the breast 
became justifiable, and his results as regards recurrence in those early days 
were very excellent. Were it necessary, it would be easy to enumerate many 
improvements and fresh operations which were carried out by him from the very 
first. Indeed much of the present operative work was directly initiated by Lister, 
although he published very little with regard to it, for as such innovations 
seemed to follow naturally from the altered course of wounds, Lister did not 
consider that the publication of improvements in individual operations was 
necessary. The great charm of Lister’s hospital work and lectures in the early 
days was not only the way in which the wounds healed, and in which the 
patients operated on recovered without pain, or fever, or illness, but also the 
fresh point of view from which every surgical affection was considered, and the 
manner in which the ancient canons of surgical practice were one by one over- 
thrown. 


poke. Rivy slOLOGY 


OBSERVATIONS ON THE 
GONTRACTILE “TISSUE OF THE IRIS 


[Quarterly Journal of Microscopical Science, vol. i (1853), p. 8.] 


Our knowledge of the cause of the movements of the iris was till within 
the last few years in a very unsatisfactory condition. That this organ possessed 
contractile fibres was a matter of inference, not of direct observation. In the 
third part of the last edition of Quain’s Anatomy, published in 1848, we find 
it stated (p. 915) that the radiating and circular fibres of the iris are generally 
admitted to be muscular in their nature, but the grounds for that admission are 
not mentioned. Mr. Bowman’s Lectures on the Eye, delivered in the summer 
of 1847, and published in 1849, show us that the then state of histology in 
this country did not enable that accomplished microscopical anatomist to 
identify the fibres of the iris with other plain (unstriped) muscular tissue. At 
p- 49 he says, ‘The fibres which make up the proper substance of the iris 
are of a peculiar kind, very nearly allied to the ordinary unstriped muscle, 
but not by any means identical with it.’ He afterwards goes on to argue that, 
as we know that the organ changes its form, and as its vessels are so distributed 
that it cannot be erectile, we have no other resource than to consider its fibres 
contractile, which conclusion he supports by reference to the striped fibres in 
the iris of birds and reptiles. 

In 1848 Professor K6lliker announced to the world his grand discovery 
of the cellular constitution of all plain muscular tissue, in a full and elaborate 
paper in the Zevrtschrift fiir wissenschaftliche Zoologie At p. 54 of the first 
part of the first volume of this journal, after speaking of the arrangement of the 


* Professor K6lliker may almost be said to have been anticipated in this discovery by Mr. Wharton 
Jones. Through the kindness of that gentleman, I have now before me two original drawings, made 
by him about the year 1843, of plain muscular tissue from the small intestine. In one of these the 
muscular fibre-cells are characteristically shown, except that their nuclei are not apparent; one of 
them is wholly isolated. In the other drawing, the alternate disposition of the fibre-cells is seen after 
the addition of acetic acid. He also observed, as he informs me, that the unstriped muscle of the oeso- 
phagus and stomach, and also of the uterus and other organs, consisted of similar elements—a fact 
which he yearly communicated to his class in his public lectures at Charing Cross Hospital. He was 
led, from appearances in the embryo, to infer that striped muscular fibre is originally composed of 
similar elements, which, in the process of development, are enclosed in a sarcolemma common to many 
of them, and become split into fibrillae. He thus accounted for the nuclei of striped muscular fibre, 
which, according to this view, are the persistent nuclei of the primitive muscular fibre-cells.—J. L. 

LISTER I B 


2 OBSERVATIONS ON THE 


fibres of the ciliary muscle, the sphincter pupillae, and dilator pupillae, he makes 
the following statement: ‘The elements of all these muscles are undoubtedly 
smooth muscular fibres. In man I have but seldom succeeded in isolating 
the individual fibre-cells, but I have had more frequent success in the case of 
the sheep, where I found them in the ciliary muscle, on an average, I-600th 
of an inch in length, and 1-4000th to 1-3000th of an inch in breadth. In man, 
in all these muscles one sees, as a rule, only parallel fibres projecting to a greater 
or less extent at the edges of small fragments of the tissue, these fibres exhibiting 
in abundance the well-known elongated nuclei, either with or without the aid 
of acetic acid. In man, the muscle of the choroid (ciliary muscle) has broader 
and more granular fibres and shorter nuclei than the iris. In the former the 
nuclei measure from 1-2400th of an inch to 1-1333rd of an inch; in the latter 
as much as I-1ogoth of an inch.’ 

Here, then, we have, so far as I know, the first and only recorded observa- 
tion of tissue in the iris identical with ordinary unstriped muscle. 

It is to be remarked that, where he alludes, in the passage above quoted, 
to having in rare cases separated the individual fibre-cells of the muscular 
tissue, Professor Kolliker speaks of the three muscles (ciliaris, sphincter, and 
dilator) collectively ; in other words, that he does not tell us in plain terms 
that he has isolated the fibre-cells of the iris at all. Now, the ciliary muscle 
is confessedly easier to deal with than the iris. Mr. Bowman, who speaks 
so doubtfully of the fibres of the iris, says of the ciliary muscle, ‘ the fibres are 
seen to be loaded with roundish or oval nuclei, often precisely similar to those of 
the best marked examples of unstriped muscle’ (op. cit., p. 53). Another very 
eminent microscopical anatomist has informed me, as the result of his experi- 
ence, that it was easy to identify the tissue of the ciliary muscle with that of 
other organic muscle, but that this had not been the case with the iris. That 
Professor Kolliker’s isolation of the fibre-cells of the muscles of the eye was 
in reality confined to the ciliary muscle is rendered probable by the fact that, 
while the whole article quoted from shows a manifest desire on the part of its 
author to give al! available detail, yet regarding the iris he mentions no facts 
requiring isolation of the fibre-cells for their determination ; while, on the other 
hand, he tells us that the fibre-cells of the iris are narrower than those of the 
ciiary muscle, and gives the length of the nuclei in the human iris—things 
which are very readily observed without isolation of the fibre-cells. His figures 
refer to the human ciliary muscle alone ; and the only measurements given by 
him of muscular fibre-cells from the eye refer to the same muscle in the sheep. 

It would seem, then, that with regard to the iris, KOlliker’s prooi falls 
short of the test of isolation of the fibre-cells. 


CONTRACTILE TISSUE OF THE IRIS 3 


An operation for artificial pupil, by excision, performed by Mr. Wharton 
Jones, at University College Hospital, on the 11th of August of the present 
year (1852), placed in my possession a perfectly fresh portion of a human iris, 
and, without knowing that Kolliker’s observations had extended to the muscles 
of the eye, I proceeded to avail myself of this somewhat rare opportunity of 
investigating the muscular tissue of the human iris. On placing under the 
microscope, four hours after the operation, portions of the tissue carefully 
teased out in water with needles, I found that some of the muscular fibre-cells 
had become isolated, and presented very characteristic appearances. I accord- 
ingly made camera-lucida sketches of the finest specimens, which are reproduced 
on a smaller scale in the accompanying figures (see Pl. I, A, Figs. 7-11). I drew 
the last cell (Fig. 8) nine and a half hours after the operation. And here I may 
mention that I have not found the muscular fibre-cells by any means a very 
perishable tissue. After an iris has been soaking two or three days in water, 
the muscular tissue of the sphincter is still quite recognisable, not only by 
the nuclei, but also by the individual fibre-cells. 

Of the figures above referred to, (7) and (8) are examples of the most 
elongated cells that I saw. By reference to the scale it will be found that the 
cell (7) is about 1-125th of an inch in length, and about 1-3750th of an inch 
in greatest breadth ; while (8) is a little shorter, but of about the same average 
breadth. Kolliker divides muscular fibre-cells into three artificial divisions, 
according to their shape, of which the third contains the most elongated and 
most characteristic cells. Of this third division, the cells (7) and (8) are good 
examples, and, in fact, correspond in their measurements to average fibre-cells 
of the muscular coats of the intestines. The cells (9) and (10), though less 
characteristic in respect of their length—(g) being about 1-333rd of an inch 
in length, and r-3000th of an inch in breadth, and (10) 1-300th of an inch by 
I-3000th of an inch—yet present the same peculiar delicate appearance and 
soft outline, and the same elongated nucleus, of not very high refractive power 
relatively to the contents of the cell, but clearly defined. All these cells have 
the same flat or ribbon-like form which is exhibited by the cell (8) at @, where 
one edge has become turned up by a folding of the cell; at 5 there seemed 
a tendency to transverse arrangement of the granules of this cell, which ten- 
dency is more strikingly exhibited at } and c in the cell (11), which, though not 
isolated, is introduced on that account. This tendency to transverse arrange- 
ment of the granules was long since noticed by Mr. Wharton Jones, as that 
gentleman has since informed me, and is, indeed, indicated in the drawings 
which are alluded to in the note above. In the cells of this iris, however, it was 
not by any means constant. Some of them, as (7) at a, and (9) at a@ and 8, 

B 2 


4 OBSERVATIONS ON THE 


exhibited something of a longitudinal arrangement of the granules, such as 
was noticed some years since in unstriped muscle by Mr. Bowman, who con- 
sidered the rows of granules as an approach to the fibrillae of striped muscle. 
These cells are more granular than I have found those of the iris of the horse to 
be ; but I may here mention that, on comparing with these drawings the out- 
line of a fine specimen of a muscular fibre-cell of the sphincter pupillae of this 
animal, which I had sketched by the camera lucida, I find it to be almost an 
exact counterpart of the cell (7) as regards the shape and size of both the cell 
and its nucleus. The nuclei of these cells measure from 1-1400th to 1-111oth 
of an inch in length, and about 1-g500th of an inch in breadth. They are not, 
however, the most characteristic that are to be found in the iris. Fig. 12 is 
from a camera-lucida sketch of a nucleus of the sphincter pupillae of a horse ; 
it measures 1-84oth by 1-15200th of an inch, and exhibits in a very marked 
manner the true rod-shaped figure which appears peculiar to muscular fibre- 
cells. On the other hand, I found some instances in the human iris of fibre-cells 
with considerably broader nuclei than those in the figures. The iris that yielded 
these cells was a blue one, apparently perfectly healthy ; it was active and 
brilliant before the operation, which was performed on account of central opacity 
of the cornea, resulting from an attack of a severe form of ophthalmia fifteen 
months previously. I watched the case closely from the first, and there was 
no reason to suspect implication of the iris in the inflammation. 

Having thus satisfactorily verified the fact of the existence in the iris 
of tissue identical with ordinary unstriped muscle, I was naturally led to inquire 
into its distribution in the organ: and, as this is a subject of great interest, 
and one about which much difference of opinion has prevailed, I may mention 
here the facts which I have hitherto observed, although there be not very much 
of actual novelty in them. 

Kolhker, in the article above referred to (loc. cit., pp. 53 and 54), describes 
a sphincter and dilator pupillae, the former ‘ very readily seen in the white 
rabbit, or the blue iris of a man, from which the uvea has been removed, about 
a quarter of a line broad in man, exactly forming the pupillary margin, and 
situated somewhat nearer the posterior surface of the iris’. Of the dilator 
he says, while confessing the difficulty of the investigation, that he believes 
it to consist of many narrow bundles, which run inwards separately between 
the vessels, and are inserted into the border of the sphincter. 

Bowman, on the other hand, states (op. cit., p. 48) that, while in some 
instances a delicate narrow band of circular fibres exists at the very verge of 
the pupil, yet, in the majority of instances, he feels swve that no such constrictor 
fibres of the pupil exist. He ascribes the contraction of the pupil to the inner 


CONTRACTILE TiSSUE.OF THE IRIS = 


part of the radiating fibres, which, he says, are joined and knotted in a plexi- 
form manner round the pupil. It is scarcely needful to observe that such 
a statement from such an authority could not but go far to impugn Professor 
Kolliker’s assertion respecting the existence of a sphincter pupillae. 

My experience, I must confess, accords with that of KOolliker, viz. that the 
sphincter is readily seen, while the dilator is that whose investigation alone 
presents very serious difficulty. In the first iris that I examined with a view 
to the distribution of the muscular tissue, I was struck, after removing the 
uveal pigment, with the appearance of a band on the posterior surface of the 
iris, near the pupil and parallel to its margin, quite evident to the naked eye, 
elastic and highly extensible. This proved to be the thickest part of the sphincter 
pupillae. I have examined six human irides with reference to the distribution 
of the muscular tissue, but in none have I had any difficulty in recognizing 
the sphincter, which I have also found equally distinct in some of the lower 
animals, viz. in the rabbit, the guinea-pig, and the horse. In man I find it 
about 1-30th of an inch in width, thickest towards its outer part, where it lies 
nearer the posterior surface of the iris than the anterior, and thinning off towards 
the pupil, where it forms a sharp margin, covered apparently on its anterior 
aspect only by some vessels and nervous threads and a delicate epitheliated 
membrane, which is thrown into beautiful folds when the pupil is contracted. 
The fibres of the sphincter are not absolutely parallel, and this deviation is 
probably produced in part by the dilating fasciculi sweeping in at various parts 
in a curved manner, and becoming blended with the sphincter. The reason 
for this supposition will appear hereafter. By teasing out under the microscope 
a portion of the actual pupillary margin, I found the sphincter to consist at 
this part of apparently unmixed muscular fibre-cells, without any connecting 
cellular tissue. Fig. 13 is a camera-lucida outline of the edge of a portion of the 
sphincter so prepared, which edge is seen to be formed of projecting fibre- 
cells, and similar appearances may be seen with great readiness under a high 
power, after stroking the pupillary margin with the point of a needle. Indeed, 
the great facility with which the tissue may be thus broken up appears opposed 
to the idea of the fibre-cells being united end to end into fibres, as the descrip- 
tions formerly given of unstriped muscle would lead one to suppose. The 
ends appear to separate as readily as the edges and surfaces, and it would rather 
seem as if the fibre-cells of a fasciculus were placed with their long axis in one 
direction, cohering generally to one another, but without the formation of 
longer fibres than each cell itself constitutes. I may here mention incidentally 
that in the circular coat of the aorta of the sheep, where the muscular tissue 
is disposed in thin layers among the elastic tissue, I have observed a distinctly 


6 OBSERVATIONS ON THE 


alternate arrangement of the fibre-cells without any formation of fibres. 
Mr. Wharton Jones’s drawing of alternately disposed fibre-cells in the small 
intestine has been alluded to in the note above. A portion of the outer and 
thicker part of the human sphincter pupillae proved also extremely rich in 
muscular fibre-cells. In the rabbit and guinea-pig the sphincter has much 
the same appearance as in man, whereas in the horse it forms a wide but very 
flat band. 

The dilating fibres of the iris present a very difficult subject of investigation. 

And here I must express my belief—a belief the result of repeated and 
very careful observations—that the fibres described by Mr. Bowman as probably 
the contractile fibres of the iris are in reality the outer cellular coats of the 
vessels. The outer coat is very abundant in the vessels of the iris, and indeed 
even in the blue eye towards the sphincter quite obscures the bore of many 
of the vessels, and prevents the recognition of their vascular character, which 
can only be determined by tracing them to their more external and more obvious 
vascular trunks. The distribution of these vessels, radiating between the 
sphincter and the circumference of the iris, and forming in the region of the 
sphincter a close and knotted plexus, corresponds accurately with Mr. Bowman’s 
description of the distribution of the fibres of the iris. His account of the tissue 
of these fibres, which he considers as probably contractile, harmonizes with the 
characters of the cellular tissue that clothes the vessels. This is peculiar ; con- 
sisting of very soft looking fibres, whose fasciculi often require the best aid of 
a first-rate glass to resolve them into their constituent elements; destitute 
apparently of yellow elastic fibres, as in the case of the cellular tissue of the 
uterus, but, like this, containing abundance of free nuclei, of roundish or 
elongated form. The fibres are completely gelatinized by acetic acid. Now 
such a tissue can hardly, in the present state of our knowledge, be regarded 
as contractile ; at any rate, if we can find any ordinary muscular tissue to 
account for the dilating action. On teasing out portions of the outer part of 
the human iris, I have found long delicate fasciculi, whose faint outline, absence 
of fibrous character, and possession of well-marked elongated nuclei parallel 
to the direction of the fasciculus, left no doubt in my mind that they were 
plain muscular tissue. 

So far my observations regarding the dilator agree with Kélliker’s, but 
whether or not these fasciculi are connected with the cellular coat of the vessels 
J have hitherto been unable to determine. 

Among the lower animals the albino rabbit and guinea-pig appeared but 
little suited for the elucidation of this point. I have been most successful with 
the eyes of a horse, where, from the thickness of the iris and the abundance of 


CONTRACTILE TISSUE OF ‘THE IRIS 7 


pigment (for the eyes were black ones), I anticipated but little result from my 
examination. Having removed the uveal pigment from behind, I found that I 
was also able to strip off from the anterior surface a tough membrane, a portion 
of which, put under the microscope, appeared to be made up of peculiar short 
felt-like fibres, which were gelatinized by acetic acid. At and near the pupillary 
margin this membrane comes off in a continuous layer, leaving a delicate 
reticular structure, which contains the muscular tissue. It also contains vessels, 
as I proved by injection, and a black network, which consists of fine fibres, 
yellow, and highly refracting, more or less encrusted with pigment. I am un- 
certain whether or not this be a network of divided nerve-tubes with adhering 
pigment ; in some spots the pigmental crust was absent from a considerable 
length of the fibres. The sphincter pupillae is beautifully seen as a broad flat 
band, of extremely well-marked, unmixed, muscular fibre-cells ; but crossing 
this at right angles are found, here and there, other flat bands of fibre-cells, 
which are in so thin a layer that without isolation the width of the individual 
cells can be seen, and they are evidently of similar dimensions to those of the 
sphincter. On addition of acetic acid their nuclei are also seen to be exactly 
like those of the sphincter. These bands divide in their course towards the 
pupil into several fasciculi, some of which cross over the sphincter at right 
angles till very near to its pupillary margin, and then seem to blend with the 
sphincter by making a slight curve. Most of the fasciculi, however, arch away 
earlier from their first course and join the sphincter in more or less oblique 
lines. The bands from which these fasciculi diverge may be traced away from 
the pupil for some distance, continuing their course at right angles to the 
sphincter till they are obscured by other tissues. Hence I think the inference 
may fairly be drawn that these are the insertions of the dilating muscular 
bundles. In the horse, then, the dilating fasciculi appear to consist of 
precisely the same tissue as the sphincter, and to blend with it in their 
insertion. The flat bands of muscular tissue above spoken of seemed to 
have no special relation to the vessels, some of which were filled with 
injection. In the outer part of the iris of the same horse I found a delicate 
muscular fasciculus lying near but not intimately connected with one of the 
radiating vessels of this part. In the human iris I have seen a muscular fasciculus, 
as it appeared from the nuclei it contained, crossing the sphincter at right 
angles for a short distance ; this observation, so far as it goes, seems to Imply 
that the same mode of insertion of the dilator occurs in man as in the horse. 

The fibre-cells of the dilator appear to be held together much more closely 
than those of the sphincter, at least in the outer part of the iris; for I have 
never been able to define the individual fibre-cells in a perfectly satisfactory 


8 OBSERVATIONS ON THE CONTRACTILE TISSUE OF THEARIS 


manner in the dilator, though I have often teased out portions of the outer 
part of the iris. The dilating muscular tissue is also probably less abundant 
than the muscular tissue of the sphincter; and this, if the fact, will help to 
account for the comparative difficulty in discovering it. I may here mention 
that both in the cat and in the rabbit, soon after death, dilatation of the pupils 
being present, exposure of one iris to the air caused it to contract at once, 
while the pupil continued dilated in the other eye, which was untouched. I do 
not know if this fact has been observed before, but it is interesting in two ways 
—first, as showing that the muscular tissue of the iris, like other muscular 
tissue, is obedient to the stimulus of exposure ; and, second, as proving either 
that the sphincter is in these animals a decidedly more powerful muscle than 
the dilator, which is equally exposed to the stimulus; or else that the fibres 
of these two muscles have different endowments, as has been shown by 
Mr. Wharton Jones to be the case with the muscular tissue of the arteries and 
veins of the bat’s wing; where, although the veins are muscular, and even 
contract rhythmically, yet the arteries alone exhibit tonic contraction when 
irritated by mechanical stimulus. 

A rich network of extremely fine fibres, seen readily in the blue human iris 
viewed from the anterior aspect, appears to represent the nerves of the organ. 
The fibres are of a yellowish colour, and are possessed of pretty high refractive 
power ; they present, if really nervous, a good illustration of the division and 
anastomosis of ultimate nerve-fibres ; the smallest divisions visible under 
a high power are seen only as fine lines. 

I have not seen any nerves in the human iris presenting the double contour ; 
but in the iris of a cat, so fresh that the tissue contracted under the needles 
as I teased it out, the double contour of the nerve-tubes was already very strongly 
marked, showing the existence in this animal of the white substance of Schwann 
in these nerves. The double contour surrounded the ends of the nerve-fibres 
which I supposed to have been broken by the teasing process. This last fact 
seemed to confirm the general belief that the double contour is a post mortem 
effect, which, however, was in this instance a very rapid one. 

I believe that a further investigation of the fresh blue iris in man, and 
of the horse’s iris, would supply the means of finally settling the question of 
the distribution of the dilator pupillae. 

My engagements do not allow me to carry the inquiry further at present ; 
and my apology for offering the results of an incomplete investigation is, that 
a contribution tending, in however small a degree, to extend our acquaintance 
with so important an organ as the eye, or to verify observations that may be 
thought doubtful, may probably be of interest to the physiologist. 


OBSERVATIONS ON THE 
MUSCULAR TISSUE OF THE SKIN 


[Quarterly Journal of Microscopical Science, vol. i (1853), p. 262.] 


AmonG the abundant new matter contained in those parts of Kdélliker’s 
Mikroskopische Anatomie that are hitherto published, there is perhaps nothing 
more striking than the announcement that small bundles of unstriped muscle 
exist in all parts of the dermis that are provided with hairs, connected in- 
feriorly with the hair-follicles, just below the sebaceous glands, and passing 
up obliquely towards the free surface of the skin. 

The effect of the contraction of such little muscles must necessarily be to 
thrust up the hair-follicles and depress the intermediate portions of skin; in 
other words, to produce cutis anserina; and thus this condition, previously 
quite unaccounted for, received at the hands of Professor Kolliker a simple 
and beautiful explanation. 

In March of the present year (1853) I made an attempt to verify this most 
interesting discovery ; and although the somewhat arduous duties of a resident 
office in University College Hospital prevented me from making the investiga- 
tion as extensive as I could have wished, yet I found myself able not only to 
verify, but in some slight degree to add to Kolliker’s observations. And as 
the main fact of the muscularity of the skin had not previously, so far as I am 
aware, found confirmation in this country, I have been induced to publish 
my results in the hope that they may prove acceptable to the microscopical 
anatomist. 

Kolliker originally described! these muscles of the skin as flat bundles 
of unstriped muscular tissue, from 1-120th of an inch to 1-75th of an inch in 
breadth, of which there appeared to be one or two in connexion with each hair- 
follicle : it seemed probable to him that they arose from the superficial parts 
of the corium, and he had clearly seen them passing obliquely downwards to 
their insertion into the hair-follicles, close behind the sebaceous glands which 
they embraced. In his Handbuch der Gewebelehre published in 1852, he gives 
in the text exactly the same account of these muscles, except that he no longer 
expresses any doubt regarding their origin from the superficial parts of the 
corium. He afterwards states in a note that these muscles had been very 


1 Vide Mikroskopische Anatomie, vol. ii, part 1, p. 14. 
* Vide Handbuch der Gewebelehve des Menschen, p. 82. 


10 OBSERVATIONS ON THE 


recently seen by two observers, Eylandt and Henle, both of whom, however, 
had found them narrower than he. Eylandt, who named them ‘arrectores pili’, 
had never seen more than one bundle connected with each hair-follicle, and 
had failed to detect muscular tissue in the nipple and areola, and in the sub- 
cutaneous cellular tissue of the scrotum, penis, and perineum, where Kolliker 
had described it as existing. Henle had traced the muscles to the most super- 
ficial parts of the dermis, where they divided into numerous little bundles 
1-3000th of aninch in diameter, which could be followed to immediately beneath 
the epidermis ; he had also seen muscular tissue in the nipple, areola, and the 
other parts where Kolliker had described it, but, on the other hand, in the 
opinion of Kélliker, he had gone too far, inasmuch as he described bundles-of 
plain muscular tissue as existing on the exterior of the sudoriferous glands 
and blood-vessels of parts destitute of hairs (such as the palm and sole). These 
K6lliker is unable to discover, and he believes that Henle has been misled by 
the use of boiled preparations, in which, as Henle himself states, fine branches 
of nerves are liable to be mistaken for muscle. Thus it appears that the con- 
firmation furnished by these two observers is by no means a very satisfactory 
one, and that Henle, the only authority on whom we rest for the fact of the 
muscles taking origin immediately beneath the epidermis, cannot, in the opinion 
of Kolliker, be implicitly relied on with reference to this investigation. It 
appears remarkable that Eylandt should have failed to discover muscular 
tissue in the scrotum, for the dartos was long since proved to owe its con- 
tractility to unstriped muscle. Of the parts in question I have examined only 
the areola mammae, which, however, answered well to the description given by 
Kolliker, who states? that the bundles of muscle are there circularly disposed, 
forming a delicate layer in the deeper parts of the corium, and encroaching 
slightly on the subcutaneous cellular tissue. On dissecting a portion of an 
areola from the subcutaneous tissue towards the surface, I found on reaching 
the deepest part of the dermis a delicate reddish-yellow fasciculus circularly 
arranged ; and a portion of this, teased out with needles, and treated with 
acetic acid, presented in a well-marked manner the nuclei of plain muscular 
tissue. A camera-lucida sketch of a small portion is given on a reduced scale 
in PLT Bi Big. - 

In enumerating the parts where he has met with muscles connected with 
the hairs, Kélliker does not mention the scalp, probably because the density 
of the tissue of this part rendered it unfit for investigation by the method in 
which he prepared his objects, viz. isolating a hair-follicle with its sebaceous 
glands and treating it with acetic acid. Its very firmness and consistence, 


? Vide Mikroskopische Anatomie, vol. li, part i, p. 14. 


MUSCUE MM TISSUE OF THE SKIN II 


however, make the scalp better adapted for fine sections than any other part 
of the skin ; and as I succeeded better with sections than by the other method, 
the scalp has received most of my attention. By compressing a portion between 
two thin pieces of deal, and cutting off with a sharp razor fine shavings of the 
wood and scalp together, moderately thin slices may be obtained. Fig. 4 
represents a perpendicular section made in this way, and treated with acetic 
acid ; the epithelium has become detached from the free surface a, ; b, c is part 
of one of the muscles near its superficial attachment, and it illustrates pretty 
well the appearance presented by them under a rather low power. They are 
distinguished from the tissue around them by their transparent and soft aspect, 
and by the abundant elongated nuclei scattered through them. Under a higher 
power the characteristic ‘rod-shaped’ nuclei become fully brought out, and 
no doubt remains as to the nature of the tissue. A good example of nuclei so 
magnified, derived from a muscle connected with a hair-follicle of the pubes, 
is shown in Fig. 5. It will be observed in Fig. 4 that the muscle has been traced 
to within a very short distance of the surface, where the nuclei became obscured 
by other tissues. 

But I afterwards found that much better sections could be obtained from 
dried specimens. A portion of shaved scalp being placed between the two thin 
slips of deal, a piece of string is tied round them so as to exercise a slight degree 
of compression ; the preparation is now laid aside for about twenty-four hours, 
when it is found to have dried to an almost horny condition. It then adheres 
firmly by its lower surface to one of the slips, and thus it can be held securely, 
while extremely thin and equable sections are cut with great facility in any 
plane that may be desired. These sections, when moistened with a drop of water 
and treated with acetic acid, are as well suited for the investigation of the 
muscular tissue, as if they had not been dried. 

Fig. r is slightly reduced from a camera-lucida sketch? of such a section, 
made in a plane perpendicular to the surface of the scalp, and at the same time 
parallel to the sloping hairs. I find that such a plane always contains the muscles 
in their entire length, the reason of which will appear shortly. In this figure 
d is the corneous, and e the mucous layer of the epithelium; 0,0... are the 
hair-follicles with their contained hairs, both have been more or less mutilated 
by the process of section; the second hair from the right being a short one, 
its bulk is seen: c,c... are the sebaceous follicles, also more or less mutilated : 
a,, a... a, are the muscles, which appear, under this very low power, merely 
as transparent streaks, and require a higher power to make out their tissue. 


? In all the sketches from which the figures that illustrate this paper have been taken, I have used 
the camera lucida, which instrument has the great advantage of ensuring correctness of proportions, 


12 OBSERVATIONS ON THE 


The muscles are seen to arise in all cases from the most superficial part of the 
corium, and to pass down obliquely to their insertions into the hair-follicles 
immediately below the sebaceous glands. It will be remarked that the muscles 
are here all on the same side of the respective hair-follicles, viz. on that side 
towards which the hair slopes: and such I found in the examination of a large 
number of sections to be always the case. This is an interesting fact, as such 
an arrangement of the muscles is exactly that which is best adapted for erecting 
as well as protruding the hairs, which must be drawn by their contraction 
nearer to the perpendicular direction. That this erection as well as protrusion 
of the hairs does occur, I have proved by artificially exciting the state of cutis 
anserina upon my own arm and leg. Tickling a neighbouring part will often 
induce horripilation, and if the eye is kept on an individual hair at this time, 
it is seen to rise quickly as the skin becomes rough, and to fall again as the 
horripilation subsides. I have never seen more than one muscle to each hair- 
follicle in the scalp ; and in order that a single muscle may by its contraction 
simply erect a hair, it must be placed in a plane perpendicular to the surface 
of the skin and parallel to the hair; this explains the fact before alluded to, 
that a section made in such a plane is sure to contain the muscles in their entire 
length if at all, while sections in other planes cut across either the muscles or 
the hairs. 

Fig. 2 represents the superficial attachments of the two muscles a, and a, 
of Fig. r ; abeing the upper end of a,, and 0 that of a,; c is the corneous, and 
d the mucous layer of the epidermis ; the intervening tissue between the muscles 
was omitted in the sketch to save time. 06 furnishes a good example of the 
subdivision of a muscle into secondary bundles near the surface, as observed 
by Henle, while in a the subdivision, if it has occurred at all, is certainly not 
carried so far: the muscle bc in Fig. 4 seems not to have undergone any sub- 
division: in some cases a simple bifurcation of a muscle near the surface is 
all that is seen: hence the splitting up of the muscles into smaller bundles 
near their upper attachment appears not to be a constant thing, and when 
it does occur, exists to a very variable degree in different muscles. Want of 
room in the plate has rendered necessary so great a reduction of the scale? 
from the original drawing, as barely to allow the nuclei of the muscles to be 
perceived ; by looking closely, however, it may be seen that at e and / nuclei 
exist immediately under the epithelium, and before introducing them into the 
sketch, I ascertained, by a higher power, that they were really of the same 
character as those in other parts of the muscles. At g it was impossible to 
trace the nuclei so far ; 1f any existed here, they were obscured by the fibrous 


’ Figs. 2, 3, and 4 have all been reduced one-half from the original sketches. 


MUSCUPAIK TISSUE. OF THE SKIN 13 


tissue of the scalp, which adheres to the muscles throughout their whole length, 
but appears to form special sheaths for the bundles of origin at the surface, 
and these sheaths interfere considerably with the examination of the muscular 
tissue enclosed by them. In some cases, however, they seem to be prolonged 
beyond the point to which the muscular tissue reaches, acting as tendons of 
attachment, and this may perhaps be the case at g: I have seen one striking 
instance of this mode of attachment, where a muscle having divided into two 
portions at some depth below the surface, a pretty long band extended like 
a cord to the surface from one of the divisions, and acetic acid having been 
added, nothing whatever but yellow elastic fibres could be seen in this band 
(the white fibres had been of course gelatinized). Asa general rule, however, 
the muscular tissue extends to within a very short distance of the epithelium, 
and often, as above stated, can be detected immediately beneath it, as Henle 
has represented. 

In Fig. 3 is shown the connexion of the muscle a, of Fig. 1, with its hair- 
follicle ; so that were the muscle a of Fig. 2 continued far enough downward, 
it would join with a of Fig. 3. The hair and its follicle are seen cut across very 
obliquely: 0 is the hair, tilted somewhat out of its natural position in the 
inner root-sheath c; d is the outer root-sheath (corresponding to the mucous 
layer of the epidermis), whose outer cells are perpendicular to the hair-follicle ; 
e is the ‘structureless layer’ of the hair-follicle ; f is the circular layer of 
Kolliker ; g the external longitudinal layer with which the muscle is seen to 
become blended. Several elongated nuclei appeared at g,; whether these are 
derived from the muscle, which is evidently inserted a good deal into the part of 
the follicle that is hidden from view, or whether they are only the elongated nuclei 
that occur in all parts of the longitudinal layer of the follicle, is doubtful: 
their well-marked elongated character inclined me rather to the former opinion ; 
h is a part of one of the sebaceous follicles, which appears to have no special 
connexion with the muscle that simply passes close by it without embracing 
it, as Kolliker implies, or sending any muscular expansion over it; and the 
same occurs in all cases, so far as I have seen; 7 is a portion of the fibrous 
tissue of the dermis, showing its connexion with the surface of the muscle. 

iXGlliker’s description of the muscles of the skin (see above, p. 9) does not quite 
accord with what I have seen in the scalp, either as regards their shape or size. 
The muscles in this part had not, in sections parallel to their course, the appear- 
ance of flatness; and by cutting slices in the way above indicated, at right 
angles to their known direction, their transverse sections were readily seen, 
and proved to be often quite circular, sometimes somewhat elliptical or poly- 
gonal, showing their form to be that of more or less rounded bundles. Their 


14 OBSERVATIONS ON THE MUSCULAR TISSUE OF THE SKIN 


average diameter is, according to my experience, I-200th of an inch, which 
is less than half the average of Kolliker’s measurements, but this discrepancy 
is probably due to difference of situation in the parts observed, Kolliker not 
having examined the scalp: for one muscle which I sketched from the pubes 
was very nearly 1-r1ooth of an inch in diameter. 

With regard to the statement of Henle, that muscular tissue exists in parts 
destitute of hairs, I have searched with diligence many good sections of both 
the palm and the sole, without having been able to discover any evidence of 
it on the exterior of either the sudoriferous glands or blood-vessels of these 
parts. In a section treated with acetic acid, the elongated nuclei of the internal 
coat of a small blood-vessel sometimes give it an appearance that might at 
first sight be mistaken for that of unstriped muscle; but this is an error 
easily avoided by care, and I cannot but agree with Kolliker in thinking that, 
in some way or other, his boiled preparations have led Henle into error. 

In order to verify Kolliker’s statement? that no unstriped muscle exists 
in connexion with the vibrissae of mammalia, I examined the feelers of a cat. 
These large hairs extend far down into the tissues beneath the skin, and have 
a more complex muscular apparatus than the small hairs of the human skin. 
Bundles of muscles extend from the lower part of the gigantic hair-follicle 
obliquely upwards to the inferior aspect of the skin, and, in addition to these, 
there is muscle surrounding the large nerve that enters the base of each hair- 
follicle. These muscles were all of the striped kind, but extremely soft and 
extensile, and among the fibres were a number of very elongated nuclei, but 
I saw no distinct evidence of the admixture of unstriped muscle. 

In conclusion, I may state that this investigation has proved to me the 
general correctness of Kolliker’s original observations, and also of the results 
of Henle’s further inquiry, except in the case of the alleged muscularity of 
parts destitute of hairs; and I shall be happy if the little additional matter 
communicated in this paper shall be found to bear as well the scrutiny of others. 


University College Hospital, June 1, 1853. 


* Vide Mikroskopische Anatomie, vol. ii, part i, p. 15. 


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ON” THE MINUTE STRUCTURE 
OF INVOLUNTARY MUSCULAR FIBRE 


[Transactions of the Royal Society of Edinburgh, vol. xxi, Part IV (1857), p. 549.] 


Read December 1, 1856. 


Ir has been long known that contractile tissue presents itself in the 
human body in two forms, one composed of fibres of considerable magnitude, 
and therefore readily visible under a low magnifying power, and marked very 
characteristically with transverse lines at short intervals, the other consisting 
of fibres much more minute, of exceedingly soft and delicate aspect, and 
destitute of transverse striae. The former variety constitutes the muscles of 
the limbs, and of all parts whose movements are under the dominion of the 
will; while the latter forms the contractile element of organs, such as the 
intestines, which are placed beyond the control of volition. There are, however, 
some exceptions to this general rule, the principal of which is the heart, whose 
fibres are a variety of the striped kind. 

Till within a recent period the fibres of unstriped or involuntary muscle 
were believed to be somewhat flattened bands of uniform width and indefinite 
length, marked here and there with roundish or elongated nuclei; but in the 
year 1847, Professor Kolliker of Wiirzburg announced that the tissue was 
resolvable into simple elements, which he regarded as elongated cells, each of 
somewhat flattened form, with more or less tapering extremities, and presenting 
at its central part one of the nuclei above mentioned. These ‘ contractile’ 
or ‘muscular fibre-cells’, as he termed them, were placed in parallel juxta- 
position in the tissue, adhering to each other, as he supposed, by means of some 
viscid connecting substance. In the following year the same distinguished 
anatomist gave a fuller account of his discovery in the first volume of the 
Zeitschrift fiir wissenschaftliche Zoologie, and described in a most elaborate 
manner the appearances which the tissue presented in all parts of the body 
where unstriped muscle had been previously known to occur, and also in situa- 
tions, such as the iris and the skin, where its existence had before been only 
matter of conjecture, but where the characteristic form of the fibre-cells, and 
of their ‘rod-shaped’ nuclei had enabled him to recognize it with precision. 
Confirmations of this view of the structure of involuntary muscular fibre were 
afterwards received from various quarters, one of the most important being 


16 ON THE MINUTE STRUCTURE OF 


the observation made in 1849 by Reichert, a German histologist, that dilute 
nitric or muriatic acid loosens the cohesion of the fibre-cells, and enables them 
to be isolated with much greater facility. In 1852 I wrote a paper ‘On the 
Contractile Tissue of the Iris’, published in the Microscopical Journal, in which 
I gave an account of the involuntary muscular fibre contained in that organ 
in man and some of the lower animals, stating that the appearances I had 
met with corresponded exactly with Kolliker’s descriptions, and illustrating 
my remarks with careful sketches of several fibre-cells from the human iris, 
isolated by tearing a portion of the sphincter pupillae with needles in a drop 
of water. In 1853, another paper by myself appeared in the same journal, 
‘On the Contractile Muscular Tissue of the Skin,’ confirming Kolliker’s recent 
discovery of the ‘arrectores pilt’, and describing the distribution of those little 
bundles of unstriped muscle in the scalp. These and other investigations into 
the involuntary muscular tissue convinced me of the correctness of K6lliker’s 
observations, and led me to regard his discovery as one of the most beautiful 
ever made in anatomy; and this is now, I believe, the general opinion of 
histologists. 

Still, however, there are those who are not yet satisfied upon this subject. 
In Miiller’s Archives for 1854, is a paper by Dr. J. F. Mazonn of Kiew, in 
which the author expresses his belief that the muscular fibre-cells of Kolker 
are created by the tearing of the tissue in preparing it, and denies the existence 
of nuclei in unstriped muscle altogether; but he gives so very obscure an 
account of his own ideas respecting the tissue, that his objections seem to me 
to carry very little weight, more especially as the appearances which he describes 
require, according to his own account, several days’ maceration of the muscle 
in acid for their development. In June of the present year (1856), Professor 
Ellis of University College, London, communicated to the Royal Society of 
London a paper entitled ‘ Researches into the Nature of Involuntary Muscular 
Fibre’. In the abstract given in the Proceedings of the Society, recently 
issued, we are informed that, ‘having been unable to confirm the statements 
of Professor Kolliker respecting the cell-structure of the involuntary muscular 
fibre, the author was induced to undertake a series of researches into the nature 
of that tissue, by which he has been led to entertain views as to its structure 
in vertebrate animals, but more especially in man, which are at variance with 
those now generally received.’ In the ‘summary of the conclusions which 
the author has arrived at’, we find the following: ‘In both kinds of muscles, 
voluntary and involuntary, the fibres are long, slender, rounded cords of uniform 
width... . In neither voluntary nor involuntary muscle is the fibre of the 
nature of a cell, but in both is composed of minute threads or fibrils. Its surface- 


INVOLUNTARY MUSCULAK FIBRE 17 


appearance, in both kinds of muscle, allows of the supposition that in both 
it is constructed in a similar way, viz. of small particles or “‘ sarcous elements ”’, 
and that a difference in the arrangement of these elements gives a dotted appear- 
ance to the involuntary, and a tranverse striation to the voluntary fibres. . . . 
On the addition of acetic acid, fusiform or rod-shaped corpuscles make their 
appearance in all muscular tissue; these bodies, which appear to belong to 
the sheath of the fibre, approach nearest in their characters to the corpuscles 
belonging to the yellow or elastic fibres which pervade various other tissues ; 
and from the apparent identity in nature of these corpuscles in the different 
textures in which they are found, and especially in voluntary, as compared 
with involuntary muscle, it is scarcely conceivable that in the latter case 
exclusively they should be the nuclei of oblong cells constituting the proper 
muscular tissue.’ 

Mr. Ellis, then, agrees with Mazonn in believing that the tapering fibre- 
cells of Kolhiker owe their shape to tearing of the tissue ; and he regards the 
nuclei as mere accidental accompaniments of the proper muscular structure, 
probably belonging to the sheath of the fibres, which, according to him, are 
of rounded form and uniform width. 

The distinguished position of Mr. Ellis as an anatomist makes it very 
desirable that his opinion on this important subject should be either con- 
firmed or refuted, and the object of the present paper is to communicate some 
facts which have recently come under my observation, and which, I hope, may 
prove to others as unequivocally as they have done to myself, the truth of 
Kolliker’s view of this question. 

In September last, being engaged in an inquiry into the process of inflam- 
mation in the web of the frog’s foot, I was desirous of ascertaining more pre- 
cisely the structure of the minute vessels, with a view to settling a disputed 
point regarding their contractility. 

Having divided the integument along the dorsal aspect of two contiguous 
toes, I found that the included flap could be readily raised, so as to separate 
the layers of skin of which the web consists, the principal vessels remaining 
attached to the plantar layer. Having raised with a needle as many of the 
vascular branches as possible, I found, on applying the microscope, that they 
included arteries of extreme minuteness, some of them, indeed, of smaller 
calibre than average capillaries. A high magnifying power showed that these 
smallest arteries consisted of an external layer of longitudinally arranged 
cellular fibres in variable quantity, an internal exceedingly delicate membrane, 
and an intermediate circular coat, which generally constituted the chief mass 
of the vessel, but which proved to consist of neither more nor less than a single 


LISTER I C 


18 ON THE MINUTE STRUCTURE OF 


layer of muscular fibre-cells, each wrapped in a spiral manner round the internal 
membrane, and of sufficient length to encircle it from about one and a half 
to two and a half times. Fig. 18 (Plate II) represents one of these vessels 
as seen under a rather low power, and shows the general spiral arrangement 
of the fibres of the middle coat. Fig. 19 is a camera-lucida sketch of the same 
artery highly magnified, in which I have for the most part traced the outline 
of the fibres on the nearer side of the vessel only, but one fibre-cell is shown 
in its entire length wrapped round nearly two and a half times in a loose spiral. 
In some other vessels the muscular elements were arranged in closer spirals, 
as in Figs. 20and 21. They are seen to have more or less pointed extremities, 
and are provided with an oval nucleus at their broadest part, discernible 
distinctly, though somewhat dimly, without the application of acetic acid. 
The tubular form of the vessels enables the observer, by proper adjustment. 
of the focus, to see the fibre-cells in section; they are then observed to be 
substantial bodies, often as thick as they are broad, though the latter dimen- 
sion generally exceeds the former. Here and there a nucleus is so placed in 
the artery as to appear in section with the fibre-cell, as shown in Figs. 20, 22, 
and 23. The section of the nucleus is in such cases invariably found sur- 
rounded by that of the substance of the fibre-cells, though occasionally placed 
eccentrically in it. From the circular form of its section the nucleus appears 
to be cylindrical. These fibre-cells are from 1-200th of an inch to 1-1ooth of an 
inch in length, from 1-2500th of an inch to 1—2000th of an inch in breadth, and 
about 1-2500th of an inch in thickness, measurements on the whole rather greater 
than those given by Kélliker for the human intestine, the chief difference being 
that in the frog’s arteries they are somewhat broader and thicker. 

Now, the middle coat of the small arteries is universally admitted to be 
composed chiefly of involuntary muscular fibre ; but in the vessels just 
described it consists of nothing whatever else than elongated, tapering bodies, 
corresponding in dimensions with Kolliker’s fibre-cells, and each provided 
with a single cylindrical nucleus embedded in its substance. Considering, then, 
that no tearing of the tissue had been practised in the preparation of the objects, 
but that the parts were seen undisturbed in their natural relations, it appeared 
to me that the simple observation above related settled the point at issue con- 
clusively. 

It was, however, suggested to me by an eminent physiologist, that the 
various forms in which contractile tissue occurs in the animal kingdom forbid 
our drawing any positive inference regarding the structure of human involuntary 
muscle from an observation made on the arteries of the frog. Being anxious 
to avoid all cavil, and understanding that Mr. Ellis’s researches had been 


INVOLUNTARY MUSCULAR FIBRE 19 


directed chiefly to the hollow viscera, I thought it best to examine the tissue 
in some such organ. For this purpose I obtained a portion of the small intes- 
tine of a freshly killed pig, selecting that animal on account of the close general 
resemblance between its tissues and those of man. The piece of gut happened 
to be tightly contracted, and on slitting it up longitudinally, the mucous 
membrane, which was thrown into loose folds, was very readily detached from 
the subjacent parts. I raised one of the thick, but pale and soft fasciculi of the 
circular coat, and teased it out with needles in a drop of water, reducing it 
without difficulty to extremely delicate fibrils. On’ examining the object with 
the microscope, I found that it was composed of involuntary muscular fibre, 
almost entirely unmixed with other tissue, reminding me precisely of what 
I had seen in the human sphincter pupillae, except that the appearances were 
more distinct, especially as regards the nuclei, which were clearly apparent 
without the application of acetic acid. Several of the fibre-cells were isolated 
in the first specimen I examined, each one presenting tapering extremities 
about equidistant from a single elongated nucleus. The fibre-cells were of soft 
and delicate aspect, generally homogeneous or faintly granular, with sometimes 
a slight appearance of longitudinal striae, such as is represented in Fig. 4. 

I had now seen enough to satisfy my own mind that the involuntary 
muscular fibre of the pig’s intestine was similarly constituted with that of the 
human iris and the frog’s artery: but before throwing up the investigation, 
I thought it right to examine carefully some short, substantial-looking bodies 
of high refractive power, which at first sight appeared, both from their form 
and the aspect of their constituent material, totally different in nature from 
the rest of the tissue. Several of these bodies are represented in Figs. 10-15. 
Each is seen to be of somewhat oval shape, with more or less pointed ex- 
tremities, and presents several strongly marked, thick, transverse ridges upon 
its surface ; and each, without exception, possesses a roundish nucleus whose 
longer diameter lies across that of the containing mass.. Yet between these 
bodies and the long and delicate homogeneous fibre-cells above described, 
every possible gradation could be traced. Figs. 8 and g are somewhat longer 
than those just indicated, and are also remarkable for their regularity. In 
Figs. 5,6, and 7 are represented fibre-cells of considerable length, marked here 
and there with highly refracting transverse bands, in the intervals of which they 
are of soft and delicate aspect. In several cells one half was short, with closely 
approximated rugae, the other half long and homogeneous. Hence it was 
pretty clear that the appearances in question were due to contraction of the 
fibre-cells, and that the shortest of these bodies were examples of an extreme 
degree of that condition ; their substantial aspect and considerable breadth 

€2 


20 ON THE MINUTE STRUCTURE OF 


being produced by the whole material of the long muscular elements being 
drawn together into so small a compass. The rounded appearance of the nuclei 
was accounted for by supposing either that they had themselves contracted, 
or that they had been pinched up by the contracting fibres, of which explana- 
tions the latter appears the more probable. 

In order to place the matter if possible beyond doubt, I prepared two 
contiguous portions of the circular coat of a contracted piece of intestine in 
different ways; the one by simply cutting off a minute portion with sharp 
scissors, so as to avoid as much as possible any stretching of the tissue, the 
other by purposely drawing out a fasciculus to a very considerable length, 
and then teasing it with needles. In the former preparation, the fibre-cells 
appeared all of them more or less contracted, except in parts where the slight 
traction inseparable from any mode of preparation had stretched the pliant 
tissue, which in the fresh state appears to yield as readily to any extending 
force as does a relaxed muscle of a living limb. In the other object, where the 
tissue had been purposely stretched, most of the fibre-cells were extended, 
and possessed elongated nuclei. Here and there one would be seen of excessive 
tenuity, scarcely broader at its thickest part than the nucleus, looking, under 
the highest magnifying power, like a delicate thread of spun glass. To how 
great a length the fibre-cells admit of being drawn out in this way without 
breaking I cannot tell. Fig. 1 represents a portion of such a fibre with the 
contained nucleus. Among these extended fibres, however, there lay, here 
and there, an extremely contracted one, the result, I have no doubt, of the 
irritation produced by the needles upon the yet living tissue. In order to guard 
against this source of fallacy, I kept a piece of contracted gut forty-eight hours, 
and then examined two contiguous parts of the circular coat in the way above 
described. The muscle was much less readily extended than in the fresh state, 
and I found that, where stretching of the tissue had been avoided as much 
as possible, it was composed entirely of fibre-cells marked with transverse 
ridges of varying thickness and proximity ; a minute fibril having, under 
arather low power, the general aspect represented in Fig. 17. But I saw no 
distinct examples of the extreme degree of contraction so frequent in muscle 
from the same piece of intestine in the fresh state. This confirmed my sus- 
picion that the latter had been induced by the irritation of the mode of pre- 
paration. On the other hand, a fully stretched fasciculus showed its fibres 
everywhere destitute of transverse rugae, so that the point was now distinctly 
proved. Kolliker, in his original article in the Zeitschrift fir wissenschaftliche 
Zoologie, figured some long fibre-cells with transverse lines upon them,‘ knotty 
swellings ’, as he termed them, which he supposed probably due to contraction, 


INVOLUNTARY MUSCULAR FIBRE 21 


and he repeats this hypothesis in the part of his Mikroskopische Anatomie 
published in 1852. The proof of the correctness of this idea is now, I believe, 
given for the first time. 

The bearings of these observations on the main question respecting the 
structure of involuntary muscular fibre are obvious and important. In the 
first place, if the short, substantial bodies were mere contracted fragments 
of rounded fibres of uniform width, we should expect them to be as thick at 
their extremities as at the centre, instead of which they are always more or 
less tapering, and often present a very regular appearance of two cones applied 
to each other by their bases. Secondly, the uniform central position of the 
nuclei in the contracted fibres, proves clearly that the former are no accidental 
appendages of the latter, to which it seems difficult to refuse Kolliker’s appel- 
lation of cells. 

The effect of acetic acid on the involuntary muscular tissue is to render 
the fibres indistinct, but the nuclel more apparent; and if this reagent be 
applied to a piece of contracted muscle, many of the nuclei are seen to be of 
more or less rounded form. The deviation of the nuclei from the ‘ rod-shape ’ 
has hitherto been a puzzling appearance, but is now satisfactorily accounted for. 

In examining a fasciculus that had been fully stretched, forty-eight hours 
after death, I met with several good specimens of isolated fibre-cells, two of 
which are represented in Figs. 2 and 3. I would draw particular attention to 
the delicate, spirally twisted extremities of the fibre-cell 3, such as no tearing 
of a continuous fibre could possibly have produced. Though these fibres are 
very long, yet we have no reason to believe that anything near the extreme 
degree of extension has been attained in them, and we cannot but contemplate 
with amazement the extent of contractility possessed by this tissue. 

In Fig. 16 is represented a portion of a fibre-cell curled up, which has been 
introduced for the sake of the clear manner in which it shows the position of 
the nucleus embedded in it. Just as in the case of the fibres wrapped round 
the arteries of the frog’s foot, this cell might be seen in section by proper adjust- 
ment, and that section is observed to be oval; proving that the fibre is not 
round, but somewhat flattened. It happens that the nucleus appears at this 
point ; its section is circular, and is surrounded on all sides by the substance 
of the cell. 

The pig’s intestine seems to be a peculiarly favourable situation for the 
investigation of unstriped muscle. Judging from Kélliker’s measurements, 
the fibres appear to be of much larger size there than in the same situation 
in the human body. The length of the fibre-cell 3 is 1-37th of an inch. The 
fibre 2 is imperfect at one extremity ; but, taking the double of the distance 


22 ON THE MINUTE STRUCTURE OF 


from its pointed end to the nucleus, its length is 1-33rd of an inch. These 
measurements are between three and four times greater than any which 
Professor Kélliker has given for the human intestine, and considerably exceed 
the length of the ‘ colossal fibre-cells’ which he describes as occurring in the 
gravid uterus. The individual fibre-cells, with their nuclei and transverse 
markings, if they have any, are quite distinctly to be seen with one of Smith 
and Beck’s ,*, object-glasses. But in order to examine their structure minutely, 


a higher power is required: that which I use is a first-rate ,’,, made several 
years ago by Mr. Powell of London. All the figures in Plate II, except 
17 and 18, are from camera-lucida sketches, reduced to the same scale. 
The principal measurements of the fibre-cells from the pig’s intestine are as 


under :— 


Length of fibre-cell, 3 . : : ; : : =z inch. 
Breadth of ditto ; 5 ; : : F Eee 
Length of nucleus of ditto . : : : ; [conn 
Breadth of ditto 5 : : : : : : SEE 
Breadth of fibre-cell, 16 ee 
Thickness of ditto : ; ‘ A : 5 ab06 
Length of fibre-cell, 13 ; ; : : Ih ; oO» 
Breadth of ditto ; : ; : : s5 Ol 
Longitudinal measurement of nucleus of ditto. : Eee 
Transverse, ditto ; ; £ ’ ‘ : : s55 
Length of fibre-cell, 15 7 : ; : ; : ee 


Hence it appears that the length of the most contracted fibre-cell is the same 
as that of the nucleus of an extended one. The fibres vary somewhat in 
breadth, independently of the results of contraction. Thus, one in the ex- 
tended condition which I sketched, but which is not here shown, measured only 
1—4000th of an inch across. The nuclei of the uncontracted fibres are very con- 
constantly of the same length, and are good examples of the rod-shape to which 
Kolliker has directed particular attention. They always possess one or two 
nucleoli, and have often a slightly granular character; occasionally, as in 
Fig. 21, they present an appearance of transverse markings. One frequently 
sees near the nucleus of a fibre that has been artificially extended from the 
contracted state, an appearance of a gap in the substance of the cell, forming 
a sort of extension of the nucleus, as if the fibre generally had been stretched 
more completely than the nucleus: an example of this is presented by Fig. 7. 
Mr. Ellis lays great stress on a dotted appearance which he considers character- 
istic of involuntary muscular fibre. I must say I agree with Kdlliker in finding 


INVOLUNTARY MUSCULAR FIBRE 23 


cd 


the fibre-cells, for the most part, homogeneous when extended, or faintly 
marked with longitudinal striae No doubt dots are present in abundance ; 
but these, so far as I have observed them in the pig’s intestine, are distinctly 
exterior to the fibres, though adherent to their surface ; and I suspect them 
to be little globules of a tenacious connecting fluid. That the fibre-cells do 
stick very tightly together may be seen by drying a minute portion of the tissue, 
after which they will be found shrunk, and slightly separated from one another, 
but connected more or less by minute threads. 

To sum up the general results to which we are led by the facts above men- 
tioned. It appears that in the arteries of the frog, and in the intestine of the 
pig, the involuntary muscular tissue is composed of slightly flattened elongated 
elements, with tapering extremities, each provided at its central and thickest 
part with a single cylindrical nucleus embedded in its substance. 

Professor Kolliker’s account of the tissue being thus completely confirmed 
in these two instances, and the description here given of its appearance in the 
arteries of the frog’s foot being an independent confirmation of the general 
doctrine, there seems no reason any longer to doubt its truth. 

It further appears, that in the pig’s intestine the muscular elements are, 
on the one hand, capable of an extraordinary degree of extension, and, on the 
other hand, are endowed with a marvellous faculty of contraction, by which 
they may be reduced from the condition of very long fibres to that of almost 
globular masses. In the extended state they have a soft, delicate, and usually 
homogeneous aspect, which becomes altered during contraction by the super- 
vention of highly refracting transverse ribs, which grow thicker and more 
approximated as the process advances. Meanwhile, the ‘ rod-shaped’ nucleus 
appears to be pinched up by the contracting fibre till it assumes a slightly oval 
form, with the longer diameter transversely placed. 

I will only further remark that these properties of the constituent elements 
of involuntary muscular fibre explain, in a very beautiful manner the extra- 
ordinary range of contractility which characterizes the hollow viscera. 


1 The longitudinal striae above referred to are probably due to a fine fibrous structure in the sub- 
stance of the fibre-cells. When in London, last Christmas, I had, through the kindness of Dr. Sharpey, 
the opportunity of examining a specimen of muscle from the stomach of a rabbit, which he had pre- 
pared after Reichert’s method. The nitric acid had not only detached the fibre-cells from one another, 
but also brought out very distinctly in each muscular element the appearance of minute parallel longi- 
tudinal fibres, which seemed to make up the entire mass of the fibre-cell except the nucleus. Ina plate 
accompanying the paper on the Iris, before referred to, I gave figures of some fibre-cells with distinct 
granules arranged in longitudinal and transverse rows. This appearance, which, however, so far as 
my experience goes, is exceptional, and is hardly sufficiently marked to deserve the appellation ‘ dotted ’, 
is probably caused by unequal contractions in the constituent material.—April 2, 1857. 


24 THE MINUTE STRUCTURE OF INVOLUNTARY MUSCULAR FIBRE 


EXPLANATION OF PLATE II 


Fig. 1 represents part of a fibre-cell from the pig’s intestine, drawn out into a very fine thread. 
and 3, fibre-cells from the same situation, considerably extended. 


Figs. 2 
Fig. 4, fibre-cells exhibiting faint longitudinal striation. 
Figs. 5, 6, and 7, fibre-cells imperfectly contracted. 


8 and 9, small fibre-cells considerably contracted. 

IO, II, 12, 13, 14 and 15, fibre-cells extremely contracted. 

16, a fibre-cell curled up, showing the position of the nucleus embedded in its substance. 

17, part of a moderately contracted fasciculus of unstriped muscle from the pig’s intestine, 
as seen under a rather low magnifying power. 

Fig. 18, a small artery from the frog’s web, under a rather low magnifying power. 

Fig. 19, part of the same vessel highly magnified, showing the spiral arrangement of the muscular 
fibre-cells. 

Figs. 20 and 21, muscular fibre-cells from another artery. In Fig. 20, the spirals are much closer 
than in Fig. 19; and in Fig. 21, the spiral is quite close. 

Figs. 22 and 23 represent some fibre-cells in arteries of extreme minuteness, and show the section 


of the nucleus surrounded by that of the fibre-cell. 


br} ba} ba} 
og 902 92 OQ OR DO 


ae | Fig 3. 


Lister del ( The Figures al magniheds9 


ON THE FLOW OF THE LACTEAL FLUID IN. THE 
MESENTERY OF THE MOUSE 


[Report of the Meeting of the British Association, Dublin, 1857, p. 114.] 


THE objects of the experiments were twofold—first, to ascertain the char- 
acter of the flow of the chyle under ordinary circumstances, which he believed 
had never yet been satisfactorily done ; and, secondly, to endeavour to throw 
some light upon the debated question, whether or not the lacteals were capable 
of absorbing solid matter in the form of granules visible to the human eye. 
In the first set of experiments,' a mouse having been put under the influence 
of chloroform an hour or two after partaking of a full meal of bread and milk, 
the abdomen was laid open by a longitudinal median incision, and a fold of 
intestine drawn out gently so that it might lie on a plate of glass under the 
microscope, the exposed part being occasionally moistened with water of the 
temperature of 100° Fahr. Under these circumstances, the lacteals were very 
readily visible as beautiful transparent beaded cords ; the beads corresponding 
to the situations of the valves, which were seen to be standing open, while chyle- 
corpuscles moved on through the tubes with perfectly equable flow, as a rule 
equal to about a quarter of that at which the blood moves through the capil- 
laries. These observations were frequently repeated, and always with the same 
result. Hence it was clear that the lacteals, though known to be muscular, 
and richly provided with valves, do not, in the mesentery at least, promote: 
the flow of the chyle by contraction, rhythmical or otherwise ; and that the 
source of the movement of the fluid is some cause in constant and steady opera- 
tion. It was further observed that the chyle-corpuscles were, many of them, 
already of full size, although at so short a distance from the scene of absorption, 
proving the rapidity with which those corpuscles are elaborated. 

The other set of experiments were performed in the same way, except that 
some coloured material, generally indigo, was mixed with the bread and milk. 
The animals took the mixture readily, and it passed freely along the intestines, 
but no indigo particles were ever seen in the chyle, although, had it been absorbed 


1 The experiments were made in 1853. 


26 LACTEAL FLUID IN THE MESENTERY OF THE: MOUSE 


in the solid form, it would have been detected with the utmost facility within 
the lacteals. It might be supposed that the colouring matter had acted as 
a poison, and paralysed the function of absorption ; but there was no appear- 
ance of this, the chyle flowing just as rapidly as when the mice were fed with 
simple bread and milk. The facts, though not perhaps absolutely conclusive, 
seemed to throw great doubt on the possibility of absorption of solid matter by 
the lacteals. 


AN INQUIRY REGARDING THE PARTS OF THE 
NERVOUS SYSTEM WHICH REGULATE THE 
CONTRACTIONS OF THE ARTERIES 


[Philosophical Transactions, Part II for 1858, p. 607.] 


Received June 18—Read June 18, 1857.' 


GREAT light has been thrown in recent times upon the nature of the in- 
fluence exercised over the blood-vessels by the nervous system. In 1852 it was 
shown by M. Bernard that division of the sympathetic nerve in the neck of 
a cat, or other mammalian, was followed by turgescence of the blood-vessels 
of the ear, and increased heat of that part and of the whole side of the face, 
together with contraction of the pupil. Early in the following year Mr. Augustus 
Waller performed the converse experiment of galvanizing the sympathetic 
above the point where it had been cut or tied, with the very striking result 
of rapid subsidence of the turgescence of the vessels, and fall of the temperature 
of the face ; while the pupil became so extremely large, as to imply that the 
dilating fibres of the iris were thrown into a state of energetic contraction. 

From these experiments it appeared to follow pretty clearly that the 
sympathetic nerve in the neck presides over the contraction of the vessels of 
the face, which, becoming relaxed and dilated when the influence of the nerve 
was removed by its division, allowed the blood to flow through them in larger 
mass than before ; but on the other hand, when excited to extreme constriction 
by the galvanic stimulus applied to the nerve, permitted but little blood to pass. 
This conclusion appears to be confirmed by the observation since made by 
Brown-Séquard, that the elevation of temperature which occurs in Bernard’s 
experiment is never greater than is to be accounted for by the increased mass 
of warm blood which must be sent through the part, on the hypothesis that the 
turgescence of the vessels is simply the result of their dilatation. It was further 
shown by Messrs. Waller and Budge, that the same region of the spinal cord 
which they had previously ascertained to preside over dilatation of the pupil, 

* This paper, and that on the ‘Cutaneous Pigmentary System of the Frog’ (p. 48 of this volume), 
were read as supplements to the ‘Essay on the Early Stages of Inflammation’ (p. 209 of this volume). 
The author has since extended his investigations into the subject of the present memoir, in accordance 
with a recommendation from the Council, and the results have been incorporated into the text, all new 


matter thus introduced being indicated as such either by date or by note at the foot of the page. 
* Comptes Rendus, vol. xxxvi, p. 378. 


28 ON THE PARTS OF "THE NERVOUS SYSTEM 


namely, the part included between the last cervical and third dorsal vertebrae, 
also regulated the vessels of the face. When that part of the cord was removed, 
turgescence of those vessels occurred ; but galvanizing the anterior roots of 
the spinal nerves proceeding from that part produced the same effect as irrita- 
tion of the sympathetic, namely, pallor with diminished temperature.’ M. Schiff 
afterwards ascertained, that after destruction of the lower part of the cervical 
and upper part of the dorsal region of the cord in bats, there is an immediate 
dilatation of the small vessels of the wings,? and Brown-Séquard had pre- 
viously shown that after transverse section of the spinal cord in the lumbar 
region in birds and mammals, an increase of 1°, 2°, or 3° Fahr. took place in 
the temperature of the paralysed parts.* All these facts tend to the same con- 
clusion, namely, that the spinal cord is the part of the nervous centres which 
presides over the blood-vessels, and that one important action at least which 
it induces in them is constriction of the circular coat of the arteries. But there 
still remains, I believe, some difference of opinion with regard to the inter- 
pretation of Bernard’s experiment ; and there might be some colour for the 
idea that the red and turgid state of the vessels seen after division of the sym- 
pathetic in the neck was due to a change in the blood, such as occurs in inflam- 
mation, and that the pallor ensuing upon galvanizing the nerve was the result 
of a return of the vital fluid to its normal condition after restoration of nervous 
influence. But all ambiguity of this kind seems to me to be removed by some 
observations made several years ago by Mr. Wharton Jones upon the frog. 
This animal is peculiarly adapted for investigations on this subject, because both 
the calibre of the vessels and the state of the blood as it flows through them can 
be observed with the utmost facility in the web ; and Mr. Jones found that divi- 
sion of the sciatic nerve was followed by dilatation of the arteries, but that this 
increase of calibre, so far from being caused by an obstruction in the progress 
of the blood, was accompanied with unusually free and rapid flow through the 
capillaries. But with regard to the part of the nervous system which regulates 
the contractions of the arteries, some more recent observations by the same 
author are at variance with the conclusion above drawn from experiments by 
others upon mammalia. For he states that the division of the roots of the 
sciatic nerve within the spinal canal failed to produce dilatation of the vessels ; 
whence it was inferred that the sympathetic fibres of the sciatic trunk, as 
distinguished from those derived from the cord, are the channels through which 

" Comptes Rendus, vol. Xxxi, pp. 377, 575- 

* Gazette Hebdomadaive de Méd. et de Chir., 1854, pp. 421, 424. 

* Experimental Researches, New York, 1853, p. 8. 


* «Essay on the State of the Blood and the Blood-vessels in Inflammation,’ by T. Wharton Jones, Esq., 
F.R.S. Guy's Hospital Reporis, vol. viii, p. 12. 


REGULATING THE CONTRACTIONS OF THE ARTERIES 29 


the stimulus is transmitted to the arterial coats." Waller and Budge’s experl- 
ments, on the other hand, appear to show that it is from the cord that the 
sympathetic derives its controlling power over the arteries. This discrepancy 
upon a matter of such great importance in physiology appeared to me to 
demand further inquiry,? and I propose in the present paper to communicate 
the result to which this investigation has led. 

The first experiment which I performed with reference to this subject 
(October 27, 1856), namely, division of the sciatic nerve on one side, gave some- 
what puzzling results. Knowing how difficult it is to judge correctly of 
differences of calibre in the vessels by mere inspection, I tied out both feet of 
a frog (under chloroform), so that a slight movement of the stage of the micro- 
scope would bring either into view, and thus, after performance of the operation 
in one limb, the other foot might serve as a standard of comparison. I then 
selected a particular artery of the left foot for measurement with the eyepiece 
micrometer, and, having noted the lmits between which its calibre varied 
during half an hour, isolated the nerve from surrounding parts by dissection, 
without any material change taking place in the diameter of the vessel. I next 
tied a piece of thread tightly round the nerve, with the effect of causing within 
the first few seconds distinct constriction of the artery, which then gradually 
expanded, and within two minutes had a larger measurement than I had 
previously observed. In other words, the effect of the ligature had been con- 
striction speedily followed by dilatation. But on examining the web half an 
hour later, I found the artery had contracted again to about its usual propor- 
tions ; after a few minutes the amount of constriction was very considerably 
greater, and continued so after division of the nerve above the ligature, and 
on looking at the other foot I found the arteries there similarly contracted. 
During the next twenty-four hours I made frequent careful comparisons of 
the conditions of the arteries in the two feet, and found that they presented 
exactly the same variations in calibre ; being sometimes closely constricted, 
at other times fully dilated in both. The constrictions generally commenced 
a very short time before a struggle of the animal, and gradually subsided when 
it had become quiet. It was thus evident that the arteries had experienced no 


1 ‘Observations on the State of the Blood and the Blood-vessels in Inflammation,’ Med. and Chir. 
Trans., vol. Xxxvi. 

* Since this paper was read, my attention has been called by Professor Goodsir to experiments 
recently performed by Pfliger. Operating upon the large edible frog of the continent (Rana esculenta), 
he succeeded in applying the galvanic stimulus to the anterior roots of the sciatic nerve within the 
spinal canal, with the effect of causing complete constriction of the arteries of the webs, Division of the 
same roots, on the other hand, was followed by full dilatation of the vessels (see Henle and Meissner’s 
Bericht, 1857). Clear proof had thus been given, before my investigation of the subject commenced, 
that the spinal system does influence the arteries of the frog’s foot. 


30 ON THE PARTS OF THE NERVOUS SYSTEM 


permanent dilatation whatever from the division of the sciatic nerve, a result 
quite at variance with the experience of previous observers. 

The explanation of this will shortly appear. On April 8, 1857, I laid 
open the spinal canal of a frog in its entire length, and divided, as I supposed, 
all the roots of the nerves coming off from the left side of the cord from 
the occiput to the sacrum, and immediately examined the webs of both feet, 
the frog being under the influence of chloroform. In the right limb the circula- 
tion was almost entirely arrested, while in the left it was going on freely. My 
attention was then diverted for half an hour, when the arteries of the right 
foot were found of medium size ; but in all the three webs of the left foot they 
were extremely dilated, appearing to have two or three times the diameter of 
those of the right limb.t This observation was of itself sufficient to prove 
that the spinal system, as distinguished from the sympathetic, does influence 
the contractions of the arteries of the frog’s foot. Here, however, as in the 
case of the divided sciatic nerve, the effects were not permanent. Six hours 
later the arteries on the left side appeared smaller than they had been, though 
still bearing marks of the operation by remaining constant in calibre, whereas 
those of the right foot exhibited very frequent variations, from pretty full 
dilatation to almost absolute closure. Next day the same state of things 
continued, the vessels of the left foot being constant in size for four minutes 
together, while in the right foot an artery exhibited about eight distinct varia- 
tions of calibre per minute as observed by micrometer; but after three days 
more they had become both small and variable in the left foot, and seemed 
to have quite recovered. On the application of galvanism to the cord, however, 
both legs were thrown into violent spasm, showing that communications still 
existed between the left limb and the nervous centre ; and it appeared probable 
that the branches which remained undivided had come after a while to supply 
more or less perfectly the place of those which had been cut. “A similar ex- 
planation seemed applicable to the speedy recovery of contractility in the vessels 
after cutting the sciatic, other nerves in the limb supplying the place of the 
divided trunk. 

In another experiment, performed on the 11th of April, the roots of the 
nerves on the right side were divided within the spinal canal, beginning at the 
head and proceeding gradually backwards. No enlargement of the vessels 
of the webs occurred until the roots of the sciatic plexus were cut, when full 


* In this and other cases of division of roots of the spinal nerves, I observed that the skin of the 
limbs supplied by the nerves cut became perfectly smooth, instead of being, as usual, rough with 
minute papillae. This appears to show that the unstriped muscular tissue of the skin is under control of 
the spinal system. 


REGULATING THE,;CONTRKACTIONS OF THE ARTERIES oT 


dilatation of the arteries of the right foot took place, one which had a few 
minutes previously varied from I to 2 degrees of the eyepiece micrometer being 
now 33° in diameter, and remaining so for ten minutes together. Half an hour 
later, however, I was astonished to find the artery again contracted to 2°, 
and not quite constant in calibre. But next day, on dissecting the animal, 
I found that some branches of considerable size between the cord and the sciatic 
plexus remained entire. 

This experiment, while confirming the proof of the influence exerted by the 
cord over the arteries of the feet, convinced me how difficult it is to make sure 
of dividing all the roots of the nerves for the hind legs within the spinal canal ; 
the operation being a very delicate one, while the parts are obscured by the 
bleeding which occurs in the living animal. At the same time the speedy 
recovery of function after partial division of the roots, pointed out a ready 
source of fallacy in such experiments. Had I deferred the examination of the 
web for half an hour in this case, there would have been no evidence of any 
effect produced on the vessels by the operation, and yet, had it not been for 
dissecting the frog, I should not have doubted that all the roots had been severed. 

Dilatation of the vessels of the webs having been found to follow division 
of the roots of the spinal nerves, it appeared important, in order to complete 
the evidence on the point at issue, to observe the occurrence of contraction 
in the arteries on irritation of the cerebro-spinal centre. For this purpose, 
on the 14th I laid open the cranium of a frog under chloroform and thrust 
a very fine needle into the cerebral hemispheres, while one of the feet was 
stretched under the microscope: no effect was, however, produced upon the 
arteries ; one selected for micrometrical observation, the largest of the web, 
measuring, as it had done before, nearly 4°, which was a state of full dilatation. 
I then treated in a similar manner the posterior dark-coloured portion of the 
brain, including the optic lobes, cerebellum, and medulla oblongata, which 
were not distinguished from one another in the experiment. As I continued 
this treatment for a few seconds, keeping my eye over the microscope, the artery 
became contracted to 1°, which was the length of a red corpuscle. The leg 
then became spasmodically extended, and the artery was carried out of the field ; 
but when I next looked at the web after removal of the needle, the vessels had 
dilated again to pretty full size. Having selected a main artery of another web 
more conveniently placed, I repeated the experiment of thrusting the needle 
into the posterior portion of the brain. This vessel, which just before, though 
by no means at its largest size, measured 23°, became contracted to almost 
absolute closure, and remained so till the needle was removed, after which it 
gradually dilated, and in three minutes measured 2°; forty seconds later 23° ; 


32 ON THE PARTS OF THE NERVOUS SYSTEM 


and about a minute afterwards 3°. The experiment was repeated several times 
with similar results, ‘the invariable rule’ (to quote from my notes) ‘ being 
contraction of the artery up to a certain point, and maintenance in the contracted 
state during the whole time, often several minutes, that the needle was stirred 
about in the brain; and then expansion, beginning almost immediately after 
withdrawal of the needle, and advancing to a certain point at which it remained 
till the needle was again introduced.’ As the brain became more and more 
broken up, the contractions grew less and less energetic, and the dilatations 
were increased, till the needle failed to produce greater contraction than from 
4° to 3°. I then thrust the needle into the spinal canal and withdrew it im- 
mediately. The hind legs started, and, after a few seconds, when I first caught 
sight of one of the webs, it was almost bloodless, and the arteries were invisible 
through extreme constriction. Four minutes later the artery before observed 
had begun to dilate and measured 1°, and after five minutes more it was 3°. 
A repetition of this experiment produced similar effects.’ 

Abundantly sufficient proof had now been obtained that the cerebro- 
spinal axis does contain a nervous centre for regulating the contractions of the 
arteries of the feet. But it was uncertain whether that centre were confined 
to any one part of the cord, or diffused extensively through it and the brain ; 
or even whether a similar office might not also be discharged by some of the 
sympathetic ganglia. With a view to determining these points, which are 
of great physiological interest, several experiments were performed, some of 
which it will be necessary to relate; but in order to make their description 
intelligible, it will be well to say a few words regarding the arrangement of 
the spinal cord in the frog. It does not occupy the entire length of the spinal 
canal, but extends backwards only seven-tenths of the distance from the occiput 


* The constriction of the arteries of the webs on irritation of the cord may be readily demonstrated 
in the following simple manner. The head of the frog being depressed so as to stretch the ligament 
between the occiput and first vertebra, a sharp knife is carried across the spinal canal immediately 
behind the head, so as to divide the cord from the brain. The toes may now be tied out and any 
observation made upon the web without the inconvenience generally produced by voluntary struggles 
on the part of the animal, while at the same time the use of chloroform is avoided; which is very 
desirable, on account of the irritating effect of its vapour on the web and the constant care required 
for its administration. If the webs be examined immediately after the operation, they will be found 
exsanguine from extreme constriction of the arteries ; but in a few minutes this state will give place 
to dilatation with free flow of blood. If now a fine needle, curved at the end, be introduced through 
the wound into the spinal canal, so that its point may penetrate a short distance into the cord, while 
the eye of the observer is kept over the microscope, the arteries will be seen to become constricted to 
absolute closure, and dilate again after withdrawal of the needle. The experiment may be repeated 
as often as may be desired till the cord becomes disorganized. 

I have lately found the above-mentioned mode of preparing the frog the best adapted also for 
experiments elucidating the nature of inflammation Little if any reflex action of the limb occurs when 
irritants are applied to the web; and if no great amount of blood have been lost in the operation, the 
creature will survive it a long while, e.g. eight days in one case. 


REGULATING DEE CONTRACTIONS OF THE ARTERIES 33 


to the sacrum, while the posterior three-tenths of the canal contain merely 
the cauda equina, including a slender filiform prolongation of the cord, which, 
though apparently composed in part of nervous matter, seems to give off no nerves. 

In the accompanying sketch of the superior aspect of the brain and cord 
of a frog, magnified two diameters, the distance from a to b represents the 
length of the spinal canal. The principal nerves for the hind 
legs spring from the cord near its extremity, but other smaller an 
branches with the same destination arise nearly as far forward ae’ 
as the middle of its length. There are also connecting fila- iA 
ments between these and some nerves for the abdominal 
parietes, taking origin slightly further forward than the middle 
of the cord. Thus the nerves for the posterior extremities 
are furnished chiefly, but not quite exclusively, from the 
posterior half of the cord. To expose the cord in its entire 
length without injury to it or any of its slender branches is 
troublesome, and also involves much loss of blood. It is 
therefore very desirable to be able to come at once on any 
part of the cord you may desire, without laying open the 
whole canal. This can be readily done from the data above 
given. The articulation between the occiput and first vertebra 
can be felt through the skin, as also can the commencement of the sacrum ; 
and the distance between these points is the length of the spinal canal. This, 
multiplied by 0-7, is the length of the cord: the requisite fraction of this 
length is then measured from the occiput and gives the place required. 

Assistance may also be derived from the circumstance that the posterior 
edges of the scapulae correspond very nearly with the mid-length of the cord, 
overlapping the posterior half by only about one-twentieth of the whole. 

To proceed with the experiments. On the 16th of April, a large frog being 
put under chloroform, the entire brain was removed about 3 o’clock p.m. without 
injury to the cord. After this operation, the arteries, which had previously 
been of pretty full size and transmitting rapid streams of blood, were found com- 
pletely contracted, so that the webs appeared bloodless except in the veins, 
and continued so for some minutes. At 3! ro™ an artery selected for special 
observation was dilating, having already attained to a diameter of 13°, and 
the circulation was returning in the web. At 3! 15™ the vessel measured 3°, 
but two minutes later was 24°, and half an hour afterwards exhibited the 
spontaneous changes in calibre commonly seen in arteries in health, the limits 
observed being 14° and 2°. It thus appeared that the removal of the brain 
had had no further effect upon the arteries than the temporary constriction 


LISTER I D 


N a 
G a a 
eer 


Beate 


34 ON THE PARTS OF THE NERVOUS SYSTEM 


induced by the irritation of the anterior part of the cord in the operation, 
followed by a brief period of dilatation. At 4", a small part of the spinal canal 
having been laid open, the anterior sixth of the cord was removed, corresponding 
to the anterior third of the scapulae. At 4" 3", when the web was first looked 
at, the artery was contracted to absolute closure, and the web exsanguine ; 
and this state of things continued till 4 7™, when the vessel began to dilate. 
At 4 8m it measured 24°, and at 4) 13™, 3°. Four minutes later it was short 
of 3°, and after five minutes more it was observed to be undergoing spontaneous 
variations of calibre from 23° to 22°. Finally, at 54 30™ its condition was 
just as it was before the experiment was performed, varying from 14° to 2°, 
without any struggle on the part of the creature, the blood at the same time 
flowing rapidly through it.1. At 64, another vertebral arch having been taken 
away, the subjacent portion of cord was removed, the canal being thus cleared 
as far back as the level of the mid-scapulae, corresponding to rather more than 
a quarter of the cord. The operation caused contraction of the artery to 1°; 
but this passed off in half a minute, and was followed by no further dilata- 
tion than to 14°, and a few minutes later the artery was again spontaneously 
varying from 1° to 14°; at the same time the heart’s action was somewhat 
enfeebled. At 65 15™ the portion of cord corresponding to another vertebral 
arch was cut away. The operation induced contraction from 14° to 3°, 
followed by gradual dilatation (in fifteen seconds) up to 12°, and this, in a few 
seconds, gave place to spontaneous contraction to 13°. By this last operation 
the vertebral canal had been cleared as far back as the posterior third of the 
scapulae, corresponding to between one-third and one-half of the length of the cord. 

At 6h 30™, having removed another vertebral arch, I divided the cord 
imperfectly, as far back as it was exposed, namely, at the level of the posterior 
edges of the scapulae, which is in the commencement of the posterior half of the 
cord ; and on looking at the web twenty seconds later, found the artery under- 
going oscillations in calibre, such as had never before been seen in it, contracting 
and dilating distinctly five times in a minute, from 1° to 14° or 14°. At 62 32m 208 
the cord was cut fairly through at the point indicated, without removal of the 
segment from the canal, and at 64 34™ the artery was found quite constricted 
and the web exsanguine. At 6h 36™ ros the artery had somewhat dilated, and 
measured 14°, but the blood was moving very slowly through the vessels, the 
heart being exceedingly enfeebled. At 6 40™ the portion of the cord was 


* The transient character of the effects produced upon the arterial calibre by these operations 
led me at first to conclude that the anterior parts of the cerebro-spinal axis did not contain any nervous 
centre for the arteries, and this view was expressed in the original manuscript. My opinions on this 
point have, however, been altered by the results of subsequent experiments, as will appear at the con- 
clusion of the paper. 


REGULATING THE CONTRACTIONS OF THE ARTERIES 


35 
detached from the roots of the nerves which sprung from it and removed from 
the canal, immediately after which the artery was found dilated to 13°, but the 
blood had ceased to move in consequence of the feebleness of the heart. 

The experiments upon this animal show that if the brain and anterior 
third of the cord act at all as nervous centres for the arteries of the feet, they 
are certainly not the only parts which possess that function; and also, that 
irritation of any part of the anterior half of the cord gives rise to contraction 
of the arteries of the webs, followed by dilatation, varying much in extent and 
duration, but generally proportioned in both respects to the previous con- 
striction. It is probable that the dilatation would have been greater after the 
last operations, had the heart been working more powerfully ; for it will here- 
after appear that a certain amount of distending force on the part of the blood 
is necessary for the vessels becoming fully expanded. 

And the 18th of April, having put a large frog under the influence of chloro- 
form, I removed a vertebral arch opposite the junction of the middle and pos- 
terior thirds of the scapulae, and then cut across the cord in that situation, 
i.e. rather more than a line anterior to its middle ; a slight retraction of the two 
segments proved that the division had been thoroughly effected. This was 
at 10 o'clock a.m. A few minutes later the arteries had recovered from the 
effects of the irritation ; one selected for special observation, having measured 
12° just before the operation, now varied occasionally between 14° and 1%°, 
and the circulation was rapid through the vessel. The next vertebral arch 
posteriorly having been removed, the cord was divided as far back as it was 
exposed, at roh 23™ 508; immediately after which the web was found ex- 
sanguine in consequence of complete closure of all the arteries, which continued 
almost in the same condition for ten minutes, at the end of which time the 
artery selected was still so small as to transmit single corpuscles with difficulty. 
At ro 35™ the portion of cord included between the points of section was 
detached from the roots of the nerves connected with it and removed from the 
canal. It measured nearly a line in length, and the posterior segment thus 
shortened proved afterwards to be only a very small fraction more than halt 
the length of the cord. The vessels afterwards relaxed slowly, so that at ro! 37™ 
the corpuscles were passing a little more freely through the artery. At rr! 15™ 
the artery measured 14°, but transmitted the blood in a very languid stream ; 
and at noon the evidences of circulation were so equivocal, that I suspected 
the creature, which was weak to begin with, to be dead, though this after- 
wards proved to be a mistake. At ob 45™ p.m. the same state of things con- 
tinued, and the artery still measured 13°, having remained unaltered in calibre 
for the last hour and a half; but I determined to try the effect of irritating 

Dee 


36 ON THE PARTS OF THE NERVOUS SYSTEM 


the posterior segment of the cord, and introduced the point of a needle a short 
distance into its anterior extremity and withdrew it immediately, keeping 
my eye over the microscope. The effect upon the artery was immediate con- 
striction, causing a retrograde stream of the blood in it for about a second, 
and then absolute obliteration of calibre. At o 49™ the artery allowed single 
corpuscles to pass through it with considerable difficulty. At 1 o’clock the 
arteries of the web were still small, but I noticed that they were undergoing 
very remarkable oscillations in calibre, just as occurred on one occasion in 
the frog last operated on, but in the present case they were more striking. I 
noted the variations for some time, and give in the following table a specimen 
of those which occurred during one minute : 


nM. Ss 
At I 2 57 the diameter of the artery was 1}°. 
At 1 3. 9g the diameter of the artery was 1°. 
At I 3 20 the diameter of the artery was 3°. 
At I 3 25 the diameter of the artery was o'. 
At r 3 38 the diameter of the artery was 3°. 
At I 3 45 the diameter of the artery was 0°. 
At I 3 50 the diameter of the artery was 4°. 


These oscillations continued for upwards of half an hour, but during the latter 
part of that time the extreme degrees of constriction were not observed. 

At 15 43™ p.m. I raised the vertebral arches from the end of the spinal canal, 
and removed the posterior half of the cord together with the cauda equina ; 
immediately after which, the artery, which for the last hour had not exceeded 
Iz, became expanded to 24°, a dimension which it had never before been 
observed to attain, except during the secondary dilatation that ensued after 
the first division of the cord when the heart was in powerful action. All the 
other arteries of the web became dilated at the same time, and remained of 
perfectly constant diameter during the hour that I continued to observe them. 
Finally, at 2h 4o I introduced a needle into the anterior part of the spinal 
canal which had hitherto been undisturbed, and irritated both the anterior 
portion of the cord and the brain, but no effect whatever was produced upon 
the vessels. 

The constriction of the arteries, which resulted in this case from irritation 
of the posterior half of the cord isolated from the rest, and the permanent 
dilatation which ensued on removal of the same part, prove that this portion 
of the cerebro-spinal axis certainly contains a nervous centre for regulating 
the contractions of the arteries of the feet. The frequently alternating contrac- 


REGULATING THE CONTRACTIONS OF THE ARTERIES 27 


tions and dilatations which occurred in this animal, as well as in the last, after 
irritation of the posterior half of the cord, are curious, and may perhaps be 
considered analogous to rapid action of the heart under the influence of stimulus. 
The fact that the arterial contractions so constantly observed to result from 
irritation of the anterior part of the cord, while it retains its connexion through 
the rest of the cord with the roots of the nerves of the hind legs, fail to occur 
after removal of the posterior two-thirds of the cord, has been confirmed by 
subsequent experiments upon other frogs. It appears to imply that if the 
brain and anterior part of the cord discharge the functions of a nervous centre 
for the arteries of the feet, they do not exert that influence through the branches 
which connect them with the sympathetic, but only through the roots of the 
nerves given off from the more posterior parts of the cord. 

On the 2nd of June, a large frog having been put under the influence of 
chloroform, the vertebral arches were removed, from the sacrum to the pos- 
terior edges of the scapulae, and at o 30™ p.m. the cord was divided imme- 
diately behind the latter situation, i.e. a little behind its middle. The left 
foot being examined shortly after, the arteries were seen to be considerably 
constricted ; one of them, which appeared to be a principal trunk, permitting 
single corpuscles to pass with difficulty, and the contraction became extreme 
after irritation of the posterior segment of the cord with a needle. The whole 
of the exposed part of the cord and the cauda equina, including the chief branches 
of nerves for the hind legs, were then removed (at o# 56™), and when the foot 
was again looked at, at 1! rom, the circulation, which had been previously 
entirely arrested by the contraction of the vessels, was going on rapidly through 
dilated arteries, the one before mentioned now measuring 3°. This, however, 
proved not to be the extreme degree of dilatation of which the vessel was 
capable ; for a stream of water at about 120° Fahr., thrown for perhaps a second 
upon the foot, induced, after brief imperfect contraction, an expansion to 
nearly 4°, which again was followed after a few minutes by a return to 3°. 
This experiment was several times repeated. In the right foot, which had 
not been subjected to the hot water, though necessarily equally affected with the 
other by the removal of the portion of cord, the arteries were found of moderate 
size at 3° 45™, having evidently recovered, to a considerable extent at least, 
their contractile power during the 2? hours which had elapsed since the operation. 
One which at this time measured 12°, became dilated on the application of 
hot water to 3°, and afterwards contracted spontaneously to 2°. 

At 4» 15™ an additional portion of the cord was removed, so as to clear the 
spinal canal as far forward as the anterior third of the scapulae. The arteries 
became at once dilated to some extent, notwithstanding that the heart’s action 


38 ON THE PARTS OF THE NERVOUS SYSTEM 


was greatly enfeebled by this operation; and at 64 45™ they had [attained 
nearly the full diameters that the hot water had before induced, while the 
circulation had somewhat recovered. Next morning the arteries of the two feet, 
the dimensions of which were before given, measured 4° and 3° respectively, 
and they continued without the slightest variation until 5! 25™ p.m.; the 
circulation meanwhile had continued to improve, and was healthy, though 
still languid. I then removed the remainder of the cord and the entire brain 
without producing any effect whatever on the size of the arteries, and they 
still measured precisely the same at Io! 45™ p.m. The following morning the 
frog was dead, and the tissues of the web had become opaque by the imbibition 
of water. 

In this case the arteries recovered their contractile power after the removal 
of the greater part of the posterior half of the cord, together with the chief 
roots of the nerves for the hind legs ; but when the part which furnishes branches 
to the posterior extremities had been completely removed, the arteries became 
permanently dilated ; and, though the circulation was then feeble, soon attained 
the full calibre which hot water had induced at a time when the heart was in 
powerful action. 

The perfect constancy with which the vessels observed maintained these 
dimensions for more than thirty hours after the operation, implied that they 
were not then at all acted on by the nervous system; and hence I was led 
at first to infer that there existed no other ganglionic apparatus for the arteries 
of the feet than that contained in the cerebro-spinal axis. 

I have since witnessed in other frogs the permanence of the dilatation 
of the arteries after removal of the brain and cord. The following case, how- 
ever, appeared at first inconsistent with these observations. On the 23rd of 
October the brain and cord of a large frog were completely removed, and an 
operation was performed upon the right thigh, which, as it turned out, tended 
to interfere with the freedom of the circulation in the webs; so that after 
twelve hours, the blood, though not presenting the appearances of inflammation, 
was almost motionless in that foot. At the same time, two arteries in one of 
the webs, which had till then remained perfectly constant in calibre, as deter- 
mined by micrometer, began to exhibit variations, and during the next twenty- 
four hours continued to change their diameter occasionally. There were, how- 
ever, certain peculiarities about these changes such as I had never before seen. 
Generally speaking, all the arteries of a web are found in the same degree of 
contraction at any one time; but here, one of the vessels under observation 


* This was the view expressed in the original manuscript, but it has been since modified by further 
experiments mentioned in the text, made, as their dates imply, subsequently to the reading of the paper. 


REGULATING THE CONTRACTIONS OF THE ARTERIES 39 


J 


was sometimes small, when the other, though in the same web, was large ; 
and not only was there no proportion between the degrees of contraction in the 
two vessels, but in one and the same artery the amount of constriction was 
very different at different parts. The unusual character of these contractions 
implied that they were caused by some unwonted circumstances; and from 
their coincidence with the almost total arrest of the blood, as well as from the 
fact that in the left foot, where the circulation continued free, the arteries 
remained of full size till the animal was destroyed, I was led to conclude that 
the puzzling appearances in question must be in some way or other dependent 
on the cessation of the flow of the vital fluid through the vessels. If this were 
so, it seemed probable that the mechanism by which these irregular contrac- 
tions were induced might be as local as their exciting cause, in which case they 
would be seen to occur in an amputated limb. In order to determine this 
point I made the following experiment. On April 2, 1858, having passed 
a knife between the brain and cord of a large frog so as to render the legs in- 
sensible, and having ascertained that the arterial constriction resulting from 
that operation had subsided, I placed a ligature round one of the thighs, and 
then amputated the limb at a higher point. The application of the ligature 
not only prevented the blood from escaping, but produced considerable tension 
in the soft parts of the thigh ; and on examining the webs, I found the arteries 
fully dilated, one which I selected for special observation measuring 43° in 
diameter. At 6 p.m., an hour and a half after the amputation, the vessel 
still maintained the same calibre, but at 7! 35™ it was slightly less, viz. 4°, 
which was still its measurement at 11 o’clock. Hitherto no change distinctly 
referable to vital contractility had taken place, but on the following morning 
the vessel-was reduced to 3° in diameter, and on the 4th of April it was of 
different sizes in different parts, viz. from 1I$° to 3°, and varied somewhat 
during the course of the day. Still more striking changes in the diameter of 
the artery appeared on subsequent days; thus the vessel was sometimes con- 
stricted to absolute closure in one part of its course, and dilated to a very con- 
siderable degree, e.g. 34°, in another part. More commonly, however, the 
artery, though never uniform in size as in health, had a general tendency either 
to moderate constriction or dilatation. The variations occurred frequently 
during the twenty-four hours, and on one occasion I saw the artery in the act 
of slow contraction at one part driving the blood into a dilated portion at a 
little distance. So late as the evening of the roth of April, i.e. during the ninth 
day after amputation, far later than vital contractility is generally believed 
to last in a limb so circumstanced, variations of calibre continued to show 
themselves; but on the 11th of April the vessel had an almost uniform width 


40 ON THE PARTS OF THE NERVOUS SYSTEM 


of nearly 3°, and exhibited no variations, while, at the same time, other 
evidences of loss of vitality in the tissues began to show themselves. The 
accompanying outlines of the calibre of a limited portion of the artery, which 
was the subject of special observation, have been made from micrometrical 
measurements selected from among a large number daily registered. They 
will serve to convey an idea of the more striking varieties of appearance pre- 
sented at different times. It may be mentioned, that the diameter of the 
vessel, when most dilated, was about 44 times the length of a red corpuscle of 
the frog’s blood. 


Be Me 
PUDYIL 9 <2 ements 6 op.m. Oe ee 
Apri 95 nccses 3 15 p.m. ea eens eres 


SUPT 7 cesses O)7 7 pn, | 22 
i ag i 


April 7 ‘dccce II 20 p.m. 


April 10)... 5 Op.m. TPS ey NEC ae es Spe eel 
Jie) SL ae 
pet eee e ee 


It must be added, that the limb was kept wrapped in clean wet lint in 
a cool place in the intervals of the observations, and that during the periods 
of examination care was taken to guard against warmth or dryness, or any 
other agency calculated to injure the delicate tissues of the webs. 

Thus irregular contractions, precisely similar to those which accompanied 
local arrest of the circulation in the experiment of October 23, took place in 
consequence of amputation of the limb; and as there could be no doubt that 
in both cases they were produced in the same manner, there was no longer 
any reason to suspect that sympathetic ganglia in the trunk might have had 
any share in their development in the former instance. Yet the circumstance 
above mentioned, that in the amputated limb the tendency to constriction 
usually affected a considerable tract of the vessel, and sometimes its entire length, 
to nearly the same degree, or in other words, that the muscular fibre-cells of 
the circular coat of the artery still contracted in concert with each other, 
seemed to imply the operation of a co-ordinating nervous apparatus contained 


REGULATING THE CONTRACTIONS OF THE ARTERIES AI 


in the limb. It appears probable that the means by which these concerted 
movements are induced are nerve-cells disseminated through the limb, in the 
same manner as Meissner has lately shown to be the case in the mammalian 
intestine.! The intestines also present a parallel to the arteries, in the fact 
that contractions of their unstriped muscular fibres result from arrest of the 
circulation in them; and I have lately shown? that these movements are not 
due to any influence exerted directly upon the contractile tissue, but that 
the intestinal nerves are essential to their production. Thus we have support 
from analogy for the view that the muscular contractions which occur under 
similar circumstances in the arteries are induced by nervous agency. 

The fact that the contraction produced in an artery of the frog’s web by 
pressure upon a particular point affects a considerable extent of the vessel, 
instead of being limited to the spot irritated, is also an argument for the 
existence of a local co-ordinating apparatus; for I find that this occurrence 
continues to take place in an amputated limb. The observation was made on 
August 4, 1858. One of the hind legs of a frog having been removed after a 
ligature had been passed round the thigh so as to prevent escape of the blood, 
pressure was made with a fine but blunt instrument over a particular point 
in the course of a large artery, whose calibre had previously been accurately 
determined by micrometer. The contractions which resulted affected the 
immediately adjacent parts of the vessel to an extreme degree; the effect, 
however, was not limited to these, but gradually shaded off in both directions ; 
and even at a considerable distance, where by ordinary observation no change 
might have been detected, the micrometer showed a diminution from 6° to 
5°,> occurring immediately upon the irritation and subsiding soon after. 
Similar results were obtained on repetition of the experiment. 

From the analogy of the intestinal and cardiac movements,’ it is probable 
that the local co-ordinating apparatus for the arteries comes into play in all 
cases of arterial contraction in the living animal, and is the medium through 
which the nerves which arise from the cord act upon the vessels. But it is 
very important to bear in mind that it is, under ordinary circumstances, in 
entire subjection to the spinal system, and only acts independently under 
special conditions of local irritation. 

It remained as yet undecided whether the nervous centre for the arteries 
contained in the cerebro-spinal axis were extensively diffused or limited to 

* Henle and Pfeufer’s Zeztschrift, 2nd series, vol. viil, 1857 
* Vide ‘ Preliminary Account of an Inquiry into the Functions of the Visceral Nerves, &c.’ (p. 90 of 
this volume). 


* These degrees have a different value from those mentioned in other parts of this paper, a different 
micrometer having been employed. * See ‘ Preliminary Account, &c.’, before referred to. 


42 ON THE PARTS OF THE NERVOUS SYSTEM 


some particular region of it. The experiments hitherto related had revealed 
nothing absolutely irreconcilable with the hypothesis of a spot about the middle 
of the cord being the special regulator of the contractions of the vessels; a view 
indicated, though by no means proved, as regards the arteries of the face and 
fore-limbs in mammalia, by the observations of Waller and Budge and of Schiff, 
alluded to at the commencement of this paper. It appeared probable that this 
point might be readily determined by removing the middle third of the cord, 
and ascertaining whether or not the arteries still retained their contractility. 
Accordingly, on August 26, 1857, having selected for measurement an artery 
in one of the webs of a frog, I divided the cord transversely at the distance 
of a quarter of its length from the posterior end, at 114 7™ a.m. During the 
next half-hour the diameter of the vessel was observed varying frequently 
from $° to 14°. At 11! 34™ the cord was again cut across opposite the middle 
of the scapulae, i.e. at a distance of a little more than a quarter of its length 
from the occiput. After this operation the artery was observed for about 
a quarter of an hour varying occasionally in calibre between 1° and 2°. At 
11» 53™ the portion of cord intervening between the two transverse incisions, 
and measuring very nearly half its entire length, was removed, immediately 
after which the artery measured 13°. At 112 55™ its diameter was 1°, the heart 
meanwhile continuing in good action, and twelve minutes later the vessel was 
again seen to change in calibre from 1° to 13° and back again to 1°. The heart’s 
action afterwards became very feeble, and the parts of the nervous centres 
concerned in regulating the arterial calibre appeared also to be failing in their 
functions, the vessel varying very slightly, and gradually increasing in diameter, 
till towards 1! p.m. its measurements were from 2° to 23°. At rh 1™ the 
posterior end of the cord was removed, immediately after which the diameter 
of the artery was above 23°, or larger than ever seen before ; at 1) 4™ it was 
near 24°, and continued so at 1" rom. Soon after this the circulation ceased 
entirely. 

In this case, notwithstanding the removal of the two middle quarters of 
the cord, the arteries were observed moderate in size and varying in calibre 
at a time when the heart was acting well. Hence it was evident that the middle 
portions of the cord are not essential to the regulation of the arterial contrac- 
tions in the feet. The following experiment confirmed this important con- 
clusion, and also furnished additional information. 

On the 20th of October, a large frog having been placed under chloroform, 


* In the original manuscript I was obliged to express my regret that time had not yet permitted 
me to carry out this idea. The dates in the text indicate that it has been done since the paper 
was read. 


REGULATING THE CONTRACTIONS OF THE ARTERIES 43 


the cord was divided transversely at the distance of about one-fifth of its length 
from the posterior extremity. At 4 20m p.m., just after the operation, an 
artery in the right foot measured 23°, the vessels appearing generally of pretty 
full size, and the flow of blood rapid through the web. At 4» 25™ the cord 
was again cut across a little behind the mid-scapulae, at a distance from the 
occiput of somewhat more than a quarter of the length of the cord. At 4» 33™ 
the diameter of the vessel was 14°. At 4» 4o™ the portion of cord included 
between the incisions was removed, without any interference with either the 
anterior or posterior segment. It was observed that a large branch for the 
hind legs, furnished by the middle segment, had to be divided during its 
removal, and immediately after the operation the artery measured 23°, and 
the flow of blood in the web was much more rapid than before. At 4) 45™ 
the artery had contracted to 2°, at 5 7™ it measured short of 2°, and a minute 
later was again 2°. At 5! r1™ [ introduced a fine needle into the anterior seg- 
ment of the cord with the effect of causing convulsive movements of the fore 
legs, but no change whatever in the calibre of the artery in the hind leg. 
I afterwards repeated this experiment twice, and the last time carried the needle 
on into the brain, and stirred it up thoroughly, but no effect was produced 
upon the vessel. At 5! 23™ the whole brain was removed, together with the 
anterior segment of the cord ; the artery, however, still continued to measure 2°. 
At this time the circulation, though somewhat enfeebled, was still pretty good. 
At 5 53™ a complicated operation was performed upon the left thigh, to which 
I need not allude further than to mention that it no doubt involved exposure 
of the other foot to a higher temperature than before, in consequence of the 
vicinity of my hands, and this was probably the cause of the dilatation of 
the arteries observed immediately afterwards, that which had been previously 
measured being now 22°. Five hours later the artery was again 2°, but the 
heart’s action was excessively languid. Next morning the circulation was going 
on steadily, though somewhat slowly, the heart having obviously recovered 
to some extent during the night. The arteries were larger than ever seen 
before ; the calibre of that above noted being 34°, and there were a good many 
blood-corpuscles adhering to the walls of the vessels. It is probable that the 
small posterior segment of the cord had become impaired in its powers, but 
that it was still acting to some extent was evident from the circumstance that 
after its removal at roh 56™ a.m., the vessel was found increased to 4°, and 
in consequence of the arterial dilatation, the stagnation of the red corpuscles, 
which existed in several parts of the webs, was almost entirely dispelled, 
although the action of the heart did not appear to have been changed. During 
the next half-hour the artery was measured four times, and was in every in- 


44 ON THE PARTS OF THE NERVOUS SYSTEM 


stance found to be still 4° in diameter. I may mention that I measured the 
posterior segment of the cord immediately after its removal, and found its length 
to be one-sixth of that of the whole cord ; it was in fact little more than the 
tip of it; but allowing for a certain amount of contraction, it may be reckoned 
as one-fifth. 

This case shows that the extremity of the cord acts as a nervous centre 
for the arteries. But the experiment of the 2nd of June proved that after the 
removal of the greater part of the posterior half of the cord, the vessels still 
remained under the control of the nervous system.1 Hence it is clear that the 
nervous centre for the arteries is not confined to any limited region of the cord. 

This experiment also indicates, in a very striking manner, how small 
a piece of the cord will suffice to regulate the calibre of the arteries, and how 
little effect may be produced, even in the first instance, by the removal of 
a large portion which also possesses that function. For it was shown, by the 
absence of contraction in the vessels when the anterior segment was irritated, 
and still more conclusively by the absence of dilatation when the anterior 
segment and the brain were removed, that the posterior segment was the only 
part capable of acting on the arteries after the removal of the middle segment ; 
or, in other words, that this operation deprived the arteries of the influence 
of the whole cerebro-spinal axis, except the posterior fifth of the cord. Yet, 
although the heart was acting powerfully at the time, the dilatation produced 
by this procedure was only moderate in amount, and very transient. Hence it 
follows that the mere fact of the speedy return of the arteries to their former 
state of contraction, after removal of an anterior portion of the cerebro-spinal 
axis, aS seen in the experiment of April 16, 1857,? is no ground whatever for 
believing that such a portion does not act as a nervous centre for the arteries. 
This being clearly understood, the invariable occurrence of contraction, when 
the posterior part of the brain or the anterior half of the cord was irritated, 
in the experiments of April 14 and 16, 1857,> must be regarded as strong pre- 
sumptive evidence, if not absolute proof, that they as well as the posterior 
half of the cord preside over the arterial contractions in the feet, although, 
as shown at p. 37, they appear to exert their influence only through those 
roots of nerves which take origin from the posterior regions of the cord. On 
the other hand, the cerebral hemispheres seem to take no part in this function, 
so far at least as it is safe to draw any inference from the negative evidence 
derived from a single experiment performed upon them, viz. that mentioned 
ab p. 31. 

The fact that the removal of a large portion of the cord is followed by 

. Midéeup. 37. . Wide: Spirsise * Vide ppengity sae 


REGULATING THE CONTRACTIONS OF THE ARTERIES 45 


only temporary dilatation of the arteries, provided that a part remains which 
furnishes roots of nerves for the posterior extremities, is in harmony with the 
transient effects which were seen to be produced upon the vessels by partial 
division of the roots of the nerves within the spinal canal in the experiments 
of April 8 and 11, 1857." In both these cases the arteries of the webs appeared 
to recover their contractile power completely, although the leg remained nearly, 
if not entirely, paralysed ; which seems to indicate that a few fibres of the 
nerves for the blood-vessels of a part can supply the place of the rest more 
perfectly than is the case with the ordinary nerves of sensation and motion. 
This peculiarity of the ‘ vaso-motor’ nerves is more strikingly illustrated by 
the first experiment mentioned in this paper”, in which 1t may be remembered 
that the arteries of the webs completely recovered their usual powers of varying 
their calibre within half an hour after division of the sciatic, although this is 
an operation which abolishes for days at least all sensation and voluntary 
motion in the leg. I have since seen yet more remarkable instances of the same 
thing. On October 10, 1857, with the view of investigating the nature of the 
control exercised by the nervous system over the actions of the pigment-cells,* 
I divided all the soft parts in the middle of the thigh of a frog, except the main 
artery and vein. The first effect upon the arteries was full dilatation; but 
about twenty-four hours later they were again of moderate size, while the 
circulation was still active. After the death of the animal, I examined with 
the microscope the coats of the artery and vein, and also the periosteum, 
together with a very slight amount of muscular tissue adhering to it, but could 
detect no nerves in any of them, although from the method of examination 
I could hardly have missed branches containing more than very few nerve- 
tubes. Comparing the result in this case with the permanent dilatation which 
always occurred after removal of the spinal cord, so long as the circulation 
continued active, it was evident that the slender filaments contained in the 
coats of the vessels, or possibly in the bone, had served as an efficient means 
of communication between the cerebro-spinal axis and the arteries of the foot. 

On the 13th of the same month I repeated the experiment upon another 
frog, operating in this case upon both thighs. In the first place, I divided 
thoroughly all the soft parts except the artery, vein and nerve, the circulation 
remaining unaffected. The nerves were then successively cut, full dilatation 
of the arteries and rapid flow through the capillaries being the immediate result. 
An hour and a half later, however, the flow was observed to be less rapid, no 


* Vide pp. 30, 31. *WNide p.520; 
* Further information regarding this experiment, as respects the pigmentary system, will be found 
in the next paper (p. 48 of this volume). 


46 ON THE PARTS OF THE NERVOUS. SYSTEM 


doubt in consequence of slight contraction of the arteries, one of which, in 
the left foot, measured 3° by micrometer, and after sixteen hours more they 
were both moderate and variable in calibre in both feet ; that in the left limb 
before noted now changing between 14° and 2°, and a principal artery in the 
right foot between 1° and 14°. The circulation meanwhile continued active, 
and remained so more than twelve hours longer ; from which circumstance 
as well as from the normal appearance of the contractions, it was evident that 
the arteries were still under the control of the cord; and I may add, that in 
another animal in which the same operation was performed upon the thigh 
after removal of the brain and cord, the arteries remained of full size and 
without variation for thirty-four hours, after which circulation ceased. 

From these facts it appears that there exists a very remarkable provision 
for ensuring the proper regulation of the arterial calibre in a part in spite of 
almost complete division of the nerves connecting the vessels with the nervous 
centre which presides over their contractions. It has been shown by recent 
discovery that sensation and voluntary motion are abolished in parts whose 
nerves have been divided, until repair has been effected by a process of fresh 
formation of the nerve-fibres. But the control of the flow of the nutrient fluid is 
not allowed to be interrupted in this manner, but continues to be exercised more or 
less perfectly, notwithstanding nearly absolute severance of nervous connexion. 

Allusion has been more than once made to the circumstance that arteries 
do not dilate so fully when the heart is very feeble as when it is in powerful 
action. This was strikingly illustrated in the case of the frog which was the 
subject of operation on April 16, 1857. Immediately after the experiments 
recorded at p. 33, the heart having ceased to cause movement of blood in 
the web, I induced complete constriction of the arteries by irritating with 
a needle the posterior part of the cord, and then thoroughly cleared the spinal 
canal of its contents. The artery under special observation did not, however, 
become dilated to a greater diameter than 14°, although during the earlier 
experiments, when the heart was acting vigorously, it had been observed to 
attain sometimes a calibre of 3°. The heart never recovered its power, and 
the vessel maintained this medium width as long as I continued to examine 
the animal, namely, three hours. 

From this and other similar observations, I infer that full dilatation of the 
arteries is a merely passive phenomenon as respects the parietes of the vessels. 
Contraction is effected by the muscular fibre-cells of their circular coat, on the 
relaxation of which the elasticity of the arteries tends to make them expand 
to a certain degree, beyond which they do not dilate, except in so far as they 
are distended by the blood. 


REGULATING THE CONTRACTIONS OF THE ARTERIES 47 


It was observed by Wharton Jones,’ that section of the sciatic nerve in 
the thigh of a frog was followed after a time by oedema of the limb and ex- 
foliation of the epidermis. If this were dependent on the dilatation of the 
arteries produced by the division of the nerve, the fact would have a very 
important bearing upon the cause of inflammatory effusion. I find, however, 
that neither oedema nor exfoliation results from permanent full dilatation 
produced by operations upon the cord or the roots of the spinal nerves ;_ while, 
on the contrary, both took place in the case of division of the sciatic, given in 
the early part of this paper, in which it will be remembered that the arteries 
recovered their contractility completely within half an hour, and presented, 
during the next twenty-four hours, precisely similar appearances with those 
in the other foot. Hence it is evident that the phenomena in question are not 
due to vascular relaxation, but to some other circumstances attending the 
operation performed upon the thigh. 

It remains to be added, that, in a healthy state of the web, no change 
in the properties of the blood was ever observed to accompany the constriction 
of the arteries on irritation of the cord, or the dilatation which followed the 
destruction of the nervous centre. The exsanguine condition of the web in the 
former case, and the turgid state of the vessels in the latter, were simply the 
effects of the variations of calibre in the arteries, the blood flowing more freely 
in proportion to their width.” 

To sum up the principal results of this inquiry, it appears— 

ist. That, of the nervous centres usually recognized, the cerebro-spinal 
axis 1s the only part which regulates the contractions of the arteries of the webs ; 
this function being apparently exercised by the whole length of the cord and 
the posterior part of the brain, operating through fibres which arise from the 
same region of the cord as do those through which sensation and motion are 
effected in the hind legs. 

2nd. That there exists within the hmb some means, probably ganglionic, by 
virtue of which the fibre-cells of the circular coat of the arteries may contract in 
concert with each other, independently of any ganglia contained in the trunk. 

And 3rd, that the local co-ordinating apparatus, though capable of indepen- 
dent action in special conditions of direct irritation, is, under ordinary circum- 
stances, in strict subordination to the spinal system; while a remarkable 
provision exists for the maintenance of this control, notwithstanding almost 
complete severance of nervous connexion between the cord and the limb. 

1 Medico-Chir. Trans., loc. cit. 
* The subject of the effect of variations in the calibre of the arteries upon the flow through the 


capillaries, will be found fully discussed in the paper ‘On the Early Stages of Inflammation’ (reprinted 
in this volume, p. 200). 


ON THE CUTANEOUS PIGMENTARY SYSTEM 
OF) DEE ERG, 


[Philosophical Transactions, Part II for 1858, p. 627. 
Received June 18—Read June 18, 1857.? 


TuHE fact that the skin of the frog is capable of varying in colour, has been 
for some years known to German naturalists. The first account of the 
mechanism by which these changes are effected, appears to have been given 
by Professor Briicke, of Vienna, in 1852,” and the subject has since been very 
carefully investigated by Dr. von Wittich of K6nigsberg,? and Dr. E. Harless 
of Munich.* All these observers describe the dark pigment as contained in 
stellate cells, each composed of a central part or body and several tubular offsets, 
which, subdividing minutely and anastomosing freely with one another and 
also with those of neighbouring cells, constitute a delicate network in the sub- 
stance of the true skin. They describe the dark contents as sometimes con- 
centrated in the bodies of the cells, at other times diffused throughout the 
branching processes, the skin of the creature being pale in the former case 
and dark in the latter. In the tree-frog the change from a dark to a pale state 
of the body generally was induced by bringing the creature into a bright light, 
by psychical excitement (as was supposed *), or by galvanizing the spinal cord ; 
and a similar effect was produced on a particular portion of the surface by 
irritating it mechanically, or with oil of turpentine, or by galvanism applied 
either directly to the part, or through branches of nerves leading to it. After 
the source of irritation was removed, the skin returned somewhat slowly to 
its former colour; and von Wittich noticed that when the paleness produced 
by direct irritation had passed off, the tint became deeper in the irritated spot 


* During the time that has elapsed between the reading of this paper and its publication, several 
new observations have been made, which it has been thought best to introduce into the text, distin- 
guished by date or footnote from the matter of the original manuscript. 

* «Untersuchungen tiber den Farbenwechsel des africanischen Chamaeleons,’ 7v. Band der mathemat.- 
naturwissenschaftl. Classe dev Kaiserl, Acad. d. Wissensch. Wien. This paper I have not yet had an 
opportunity of consulting. 

* Miiller’s Archiv, 1854. 

* Zeitschrift fiiy wissenschaftliche Zoologie, vol. v, 1854. 

° This rests on the authority of von Wittich ; but, for anything stated to the contrary in his paper, 
the effects ascribed to psychical excitement may have been connected with the efforts of the creature in 
struggling, independently of any emotional change. 


ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 49 


than elsewhere. The esculent frog exhibited similar phenomena, but was less 
sensitive. The concentrated state of the pigment is attributed by all the 
observers above named to contraction of the cells, while the diffused condition 
is supposed due to their relaxation. The contents of the cells are described 
as dark granules suspended in a fluid; and both von Wittich and Harless 
have distinctly seen the granules rolling along in the offsets during the process 
of concentration. All the authorities agree in the opinion that the fluid 
and granules move together from one part of the cell to another, the offsets 
being supposed empty of both when the pigment is accumulated in the body 
of the cell.’ 

In some respects the above description agrees with my own experience 
of the common frog of this country (Rana temporaria). I find that this well- 
known animal exhibits changes of hue almost as great as those of the chameleon, 
every specimen being capable of varying from a very pale to a very dark colour, 
the former being generally greenish yellow, but in some varieties reddish ; 
and the latter brownish black, or sometimes coal black ; while between these 
extremes any intermediate shade may be assumed. The depth of tint is 
generally proportioned to that of surrounding objects: thus a frog caught 
in a recess in a black rock was itself almost black ; but after it had been kept 
for about an hour on white flagstones in the sun, was found to be dusky yellow, 
with dark spots here and there. It was then placed again in the hollow of 
the rock, and in a quarter of an hour had resumed its former darkness. These 
effects are independent of changes of temperature ; for similar results may 
be obtained by placing a frog alternately in a vessel from which luminous rays 
are excluded, and in a white earthen jar covered with glass, in the same situa- 
tion. Different examples, however, differ much in their sensitiveness to light. 
A violent struggle on the part of the animal is often followed by a speedy 
alteration from a dark to a pale state of the skin. It seems very doubtful 
whether psychical excitement has anything to do with this occurrence, any 
more than with the arterial contraction which invariably takes place under 


1 From the way in which von Wittich alludes to Briicke’s description, it is clear that the latter 
supposed the cells to be contractile. Von Wittich himself in his first paper speaks of the movement 
of the pigment induced by galvanism as ‘ satisfactorily’ showing ‘that the stellate pigment-cells are 
contractile’. In his second paper (vide Miiller’s Archiv, 1854, p. 263), he expresses some doubt regard- 
ing the contractility of the ce//-wadl, but clearly speaks of the contents (fluid and granules) as moving 
together. Harless, after describing ‘the rolling of the pigment-molecules towards the centre of the 
cell’, goes on to say, ‘ that this rolling may be possible, there must be a fluid in the cells and offsets, 
to which the molecules owe their movement.’ He takes it for granted that the movement of the fluid 
must be due to some contractile agency, and as he finds no apparatus of this nature around the cells, 
and as the unstriped muscular fibres of the skin have no special relation to them, he infers that the 
cell-wall is itself contractile. 


LISTER I E 


50 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


such circumstances. Neither oil of turpentine nor galvanism, when applied 
to the integument, produces, so far as I have seen, any effect upon its colour ; 
our species being little influenced in this respect by direct irritation. I have, 
however, frequently observed, after forcibly pinching a dark web, that a pale 
ring, about one-sixteenth of an inch in breadth, has formed around the area so 
treated ; but this was very slow in appearing, being first noticed from half an 
hour to an hour after the pinch was given. 

The webs of the hind feet, examined under a low power of the microscope, 
exhibit differences in the distribution of the dark pigment? according to the tint 
of the skin, such as will be understood by referring to Plate III (p. 68), where 
Fig. i is from a dark portion of web, and Fig. 2 from a pale part in the same 
animal. In Fig. 2 the colouring matter is seen to be collected in black spots 
of irregular angular shape. This, however, is not the state which exists when 
the colour is palest, for then the masses of pigment are in the form of round 
dots, as in the part to the right in Fig. 1, Plate V (p. 274). Neither does Fig. 1 
of Plate III give the condition met with when the skin is darkest, in which case 
all that meets the eye on superficial observation is a reticular appearance, 
such as is represented in the stripe down the middle of Fig. 1, Plate V, and 
in the lower part of Fig. 2 in the same Plate. When the colour of the integu- 
ment is about medium, the pigment is disposed in a truly stellate manner, 
as on the left side of Fig. 1, Plate V. It may be convenient for the purposes 
of description, to designate these various states as respectively the dotted, 
angular, stellate, and reticular conditions of the pigment. 

When a higher magnifying power is applied in an extremely dark state of 
the skin, the chromatophorous cells, for such they seem to be, appear as depicted 
in Plate III, Fig. 3, where two of them are given, along with an adjacent capillary 
distended with blood-corpuscles. Each cell consists of a somewhat flattened 
central part with several irregular offsets, of considerable diameter near the 
central part, but speedily breaking up into small branches. The ultimate 
ramifications, some of which are of extreme minuteness, anastomose freely 
with one another and with those of neighbouring cells, constituting a very 
delicate and close-meshed network, which pervades the whole thickness of the 


‘ Other kinds of pigment are also present in the skin of the common frog, generally of yellow colour, 
but sometimes red. My attention has not been much directed to these, but I have noticed that they 
are contained in receptacles of the same general form and structure as those which hold dark pigment ; 
and on one occasion, since the reading of the paper, I observed the colouring matter disposed in a stellate 
manner with complex ramifications in one part of a web, and in another part collected into round spots ; 
implying that these cells possess the functions of concentration and diffusion of the pigment. They 
do not, however, always act in harmony with the dark cells ; and it is probably through their agency 
that changes in tint, such as I have seen to occur in one and the same frog, independent of mere lightness 
and darkness of shade, are produced. 


ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 51 


true skin, and especially follows the course of the blood-vessels, entering into 
the composition of the cellular coat of the arteries and veins, and twining about 
the capillaries in a very remarkable manner. The walls of these cells and of 
their tubular offsets appear to be extremely delicate, and some attempts which 
I have made to isolate them from surrounding tissues have barely served to 
demonstrate their existence. The cells vary considerably in dimensions accord- 
ing to the size of the animal; thus, those in Figs. 8,9, and 10, which are from 
young frogs, though magnified 500 diameters, show in the drawing even 
smaller than those in Fig. 3, magnified only 250 times, the latter being from 
a full-grown specimen. In an average full-sized cell of a large frog, the middle 
portion was found to measure I-330th of aninch in length by 1-670th of an inch 
in breadth, and 1-1500th of an inch in thickness. The last-named dimension was 
obtained by carrying the focus of an object-glass of high power, from the most 
superficial to the deepest part by the screw for giving slow motion, and reading 
off on its graduated circle the number of divisions traversed, these having 
a known proportion to the depth measured. Opportunities for testing the 
correctness of this measurement were presented by other cells which lay edge- 
wise, so that their thickness could be observed directly. 

Perhaps the strongest argument in favour of the cellular nature of these 
receptacles of colouring matter is afforded by the universal presence of a nucleus 
in the central cavity of each. In large frogs it is often difficult or impossible 
to discover clear evidence of it, but in small ones, in which the web is much 
thinner and its constituent parts therefore capable of clearer definition with 
the microscope, it can be quite distinctly seen in the reticular condition of 
the pigment. Its form and relations may be gathered from Figs. 8,9, and Io. 
In Sand ro the bodies of the cells are viewed on the flat, and the nucleus appears 
as an oval colourless body, about I-2500th of an inch long by 1-3300th of an 
inch broad. In Fig. 9 the body of the cell is seen edgewise applied to the wall of 
a capillary blood-vessel, which is embraced by its processes. The thickness of 
the nucleus is thus displayed, and is shown to be equal to that of the cell in 
which it lies, which in fact it causes to bulge slightly, and also nearly as great 
as the breadth of the nucleus in Figs. 8 and ro. In the cell of Fig. 10, the 
thickness of the nucleus, measured in the manner above described, was found 
about equal to its breadth. The nucleus in Fig. 8 is not centrally placed 
in the body of the cell, and I have in some other cases seen it still more 
eccentric.? 


The contents of these cells are very minute dark granules or molecules sus- 


* The precise relations and dimensions of the nucleus have been ascertained subsequently to the 
reading of the paper. 


E2 


52 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


pended in a colourless fluid, in which I have often seen them moving freely : 
when in considerable mass they produce a jet-black appearance, but exhibit 
a brown tint when present only in small quantity. 

When the skin of the animal is very pale, the colouring matter is all 
accumulated in the central parts of the cells. With regard to the method in 
which this change is effected, I am compelled to differ altogether from the 
before-mentioned authorities, who suppose that the granules and fluid are 
together forced by contraction from the processes into the bodies of the cells. 
They seem to take it for granted that the depth of tint of any one part of a cell 
depends simply upon the bulk of the contents situated there, and the consequent 
thickness of the coloured medium through which the light passes before reaching 
the eye. This, however, is by no means the case, as may be seen by referring 
again to Plate III, Fig. 3. The pigment is there represented fully diffused 
through the ramifications of the offsets, and some of the smallest of these are 
darker than the bodies of the cells and the adjoining broad parts of the pro- 
cesses; yet the former are far from being thicker than the latter: on the 
contrary, some of the branches, though conspicuous for their blackness, appear 
but as delicate lines which can be seen only at one focus when a glass of very 
high power is employed; while the bodies of the cells, as above mentioned, 
possess considerable thickness, and the processes are not flat, but subcylin- 
drical. But the differences in tint are sufficiently accounted for by the cir- 
cumstance that in the dark branches the colouring particles are closely packed 
together, whereas in the bodies of the cells and the paler parts of the offsets, 
the individual granules are separated from one another by considerable colour- 
less intervals. Hence it is clear that the degree of darkness of any part of a cell 
does not depend so much on the bulk of its contents in the aggregate, as on the 
proportion which the pigment molecules in it bear to the fluid in which they are 
suspended. 

If the whole contents of the processes were forced into the central parts 
during concentration of the pigment, and driven back again during diffusion, 
the bodies of the cells would be subject to great variations in capacity, becoming 
turgid in concentration and collapsed in diffusion; and the bulk of the 
central coloured mass would be great in the former case, but small in the latter. 
The very reverse, however, really takes place. Fig. 6 represents the appearance 
of the pigment in a concentrated condition, in one of the same cells which in 
Fig. 3 show it in full diffusion. During the time in which this change took place, 
the adjacent capillary had shrunk to about half its former size, but it will be 
recognized by its general form, and will indicate which of the two cells is that 
under consideration. Both the figures were drawn on the same scale with the 


ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 53 


camera lucida,! so that accuracy of proportion is ensured. The circular black 
mass into which the colouring matter is now all collected, measures less across 
than either the length or breadth of the body of the cell in the diffused state 
of the pigment. Further, the mass is not spherical, but of flattened form, and 
its thickness is only about that of the central part of the cell in diffusion. This 
we know from the appearances presented by the spots of concentrated pigment 
in other cells seen edgewise, as is the case with some in Fig. 7, which represents 
the outline of the wall of a large blood-vessel, and the pigment contained in 
its external coat in nearly complete concentration. Hence it appears that 
all the pigment-granules contained in the body of the cell and the minutely 
ramifying processes in the diffused state, have been brought together into a space 
considerably less than was then occupied by the pale contents of the body of 
the cell alone. The coloured particles have been concentrated into a dense 
disciform mass, but the fluid in which they were suspended has been left 
behind. 

Fig. 4 shows the pigment in the same cells as Fig. 3 in an intermediate stage, 
in which the process of concentration is about half accomplished ; the upper 
one being in the condition which would appear stellate under a low magnifying 
power. The greater part of the pigment is collected in the bodies of the cells, 
especially towards their central parts: in the middle of each dark mass, how- 
ever, 1s a pale spot, doubtless due to the circumstance of the granules not having 
yet insinuated themselves between the cell-wall and the nucleus, which, as shown 
above, probably lies in contact with it. This appearance of pale central points 
was very general in the web at the time when Fig. 4 was drawn, but gradually 
disappeared as the aggregation of the pigment-molecules proceeded, and does not 
exist in Fig. 5, which represents the lower of the two cells in a more advanced 
state of concentration. The remote branches of the processes were then for the 
most part invisible, and those which did appear were generally pale, instead ~ 
of dark, as they had been during full diffusion. This difference does not depend 
on contraction of the branches, but on the granules being absent from them, 
or sparsely scattered instead of closely packed; and I have often ascertained 
from some granules remaining widely separated in a process, that it was of 
large calibre, though, without careful searching, it would have seemed invisible 
Even in Fig. 6 concentration is not represented absolutely perfect ; for a few 
molecules are to be observed near the black mass in the more circumferential 
parts of the body of the cell. The extreme delicacy of the cell-wall makes it 
very difficult to trace it among the surrounding tissues, and I have not attempted 


1 All the drawings in the plate which accompany this paper were made with the assistance of 
this very valuable instrument. 


54 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


to give it in these figures, which, it must be clearly borne in mind, represent 
only the colouring matter. The external parts of the body of the cell and the 
principal processes may, however, be sometimes discovered, though perfectly 
colourless in consequence of concentration: they are then found to be of the 
usual dimensions met with in full diffusion, showing that they are still full of 
fluid though destitute of granules. In fact the only change of form to which 
the cells appear liable is a slight bulging of the central part at the seat of the 
black mass in the concentrated state, which I have detected in some cases by 
camera-lucida sketching, and which is consistent with the separation of the 
cell-wall from the nucleus, implied by the ultimate disappearance of the central 
pale points of Fig. 4. 

The movement of the granules towards the centres of the cells may be seen 
without any great difficulty. The death of a healthy frog is always followed 
by complete concentration of the pigment for a time, however much diffused 
it may have previously been, and the process taking place gradually, its progress 
can be observed. Ifa frog with the skin dark, and the pigment therefore diffused, 
be killed and the web examined soon with a good glass of high power, the 
granules may be seen distinctly moving along the offsets of each cell to join 
the dark mass which is becoming accumulated in the central part. If the 
process is going on languidly, the individual molecules advance slowly with 
slightly dancing movements, indicating that they are free in the fluid and 
not confined in any way to the cell-wall. If concentration is taking place 
more speedily, the granules rush along so quickly that no time is allowed 
for observing their molecular movements, and often their motion is so rapid 
as to elude the eye altogether. In one instance a large-sized offset, which 
at first contained abundance of pigment, became gradually cleared in this 
way of its colouring matter without any change in its dimensions, till it was 
almost invisible on account of the very small number of molecules remaining 
in it. 

It is thus a matter of direct observation, that the pigment-granules move 
along into the bodies of the cells during concentration, and leave colourless fluid 
behind them in the processes. It is clear that their motion cannot be explained 
by currents in the fluid; for streams proceeding towards the centre of a cell 
would necessarily be accompanied by a returning flow in the opposite direction, 
which would carry the pigment with it unless the molecules had a special 
tendency towards the centre. The circular form assumed by the mass of pig- 
ment when concentration is complete is strongly suggestive of a central attractive 
force acting on the granules. The occurrence of the central pale points, which 
are represented in Fig. 4, showing that the nucleus was there in the middle of 


ON THE CUTANEOUS: PIGMENTARY SYSTEM OF THE. FROG 55 


the concentrating pigment, led me at first to suppose that this body was the 
attractive agent. I afterwards took pains to ascertain whether the nucleus 
always has this relation to the mass, and found that such is not the case. On 
October 22, 1857, I watched three adjacent cells during the process of post 
mortem concentration; in two of them the nucleus ultimately projected by 
about a quarter of its length at one side from the black spot, while in the other 
cell the aggregated molecules covered only one-third of the nucleus, so that 
no part of that body lay in the middle of the mass. The point to which the 
granules appear to havea special tendency is the middle of the body of the cell, 
which seems always to correspond with the centre of the disc of molecules, 
whereas the nucleus is often eccentrically placed in the cell. 

The diffusion of the molecules is not merely a passive result of the cessation 
of concentration, as has been hitherto supposed. In watching closely the occur- 
rence of the phenomenon, I have seen? the granules start off suddenly from 
the central mass, with a velocity which implied that they were under the in- 
fluence of forces very different from those which cause molecular movements 
in them when shed from their containing cells. That the process requires the 
vital forces of the cells to be in full operation is also proved by the fact that 
any agency, such as a galvanic shock, which temporarily paralyses their func- 
tions, arrests diffusion as well as concentration ; whereas, if the former were 
merely passive, it would take place as soon as the concentrating power was set 
at rest. 

I have already pointed out the sparsely scattered state of the granules 
in the central receptacles, compared with their accumulation in the branches 
of the offsets, in the fully diffused state shown in Fig. 3. This contrast is some- 
times much more striking, so that the bodies of the cells are almost colourless, 
and require some experience with the tissue in order to detect them. This 
indicates a special tendency on the part of the granules to leave the middle 
of the cell. Yet to however great a degree diffusion be carried, there always 
remain some molecules in the body of the cell uniformly distributed throughout 
its thickness and not attached to the parietes, as they would have been had 
their dispersion been caused by attraction on the part of the cell-wall. This 
disposition of the granules, which obtains even in the immediate vicinity 
of the nucleus, appears also distinct evidence against the operation of a central 
repulsive force ; for this would render the body and the adjoining parts of the 
processes as clear of pigment as the remote branches are made in concentration. 


* This was the view expressed in the paper as it was read. 
* This observation was made after the reading of the paper. 


56 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


The hypothesis which would seem most consistent with the appearances 
described, is that of a mutual repulsion on the part of the pigment-granules, 
induced by some agency strongest at the centre of the cell and feeble in the 
remotest branches of the offsets. 

On October 27, 1857, I was observing a cell in which post mortem concen- 
tration had occurred, the pigment being in the angular condition. At one of 
the angles movements of the granules were going on, of which I will content 
myself with giving two examples. At one time a number of molecules started 
off together with great rapidity from the black mass, but stopped after having 
proceeded a certain distance, some of them remaining in their new position, 
while others returned at various rates towards the centre. At another time 
an individual granule moved slowly away for a little space, and then came 
back by a circuitous route to a different part of the mass from that which it 
had left. What I then saw has led me to believe that the movements of the 
pigment-molecules are of a complex character that will perhaps never be fully 
explained. In the meantime it is clear that concentration and diffusion are 
both active vital functions, and that both imply peculiar relations of the centre 
of each cell to the pigment-molecules, as distinguished from the fluid in which 
they are suspended. 

These conclusions invest the pigmentary changes with deep physiological 
interest. In the movements of the granules towards and from the centres of 
their containing cells, we now have ocular demonstration that a particular kind 
of material may have impressed upon it by vital action, independently of 
muscular contraction or ciliary motion, tendencies to rush energetically to or 
from certain fixed points in the tissues, through distances equal to nearly twice 
the thickness of a villus of the human intestine, and several times greater than 
the average breadth of a human capillary interspace. Whether we be able to 
explain the means by which such results are accomplished or not, it is obvious 
that forces of similar powers and range of operation, if suitably modified 
according to the circumstances of each case, would be more than adequate 
to cause the passage of particles of fat from the cavity of the intestine into 
the central lacteals of the vill, or the transit of the material required for 
a particular secretion or act of nutrition out of a capillary into a neighbouring 
gland cell or other portion of tissue; and, again, for the discharge of an elaborated 
product of secretion into a duct, or the return of waste matter into the blood- 
vessels or lymphatics. We thus obtain a basis of fact for what has hitherto 
been merely conjectural, in the explanation of the processes of absorption, 
secretion, and nutrition generally. 

The functions of the pigment-cells are under the control of the nervous 


ON THE CUPANEOUS  PIGMPNTARY SYSTEM OF THE FROG 57 


system,’ as is evident from the effects produced on the colour of the skin by 
a struggle on the part of the animal. 

Much attention has been devoted by von Wittich to the inquiry, by what 
ganglionic centres this control is exercised. He found that division of the 
sciatic nerve in the thigh, or of cutaneous branches in the dorsal region, did 
not prevent the parts of the skin supplied by them varying in colour along 
with the rest of the body under the influence of light ; and, supposing that in 
such operations all connexion was severed between the portions of integu- 
ment concerned and the central organs of the nervous system, he inferred 
that the pigmentary changes induced by light were effected independently 
of either the cerebro-spinal axis or the usually recognized sympathetic ganglia. 
He nevertheless regarded such variations as probably reflex in their nature, 
and attributed them to a peripheral ganglionic apparatus in the skin itself; 
and this opinion appeared confirmed by the circumstance that direct irritation 
operated in the same manner upon the colour of a detached piece of integument 
as upon that of the living animal. At the same time, as he observed paleness 
of tint to result from irritation of the cord, or of the nerves distributed to a parti- 
cular part of the surface, he concluded that the spinal system was also capable 
of acting on the pigment-cells, and so accounted for the supposed influence of 
psychical excitement upon the tint of the skin. Thus, according to his view, the 
cutaneous pigmentary system was circumstanced like the heart or intestines, 
which, though possessing the faculty of independent action by virtue of their 
intrinsic ganglia, may also have their movements affected by mental emotion. 

In the course of some experiments performed in April 1857, with reference 
to the influence exerted by the cord upon the calibre of the arteries, I noticed 
on two occasions that partial division of the roots of the nerves for one of the 
hind legs within the spinal canal was immediately followed by increased pale- 
ness of the limb, of transient character, after which the leg assumed precisely 
the same colour as the other, this result being in accordance with von Wittich’s 
description. But I further observed in two cases in which such operations 
had been performed, that when a considerable time had elaspsed, viz. nine hours 
in one instance and two days in the other, the limb whose nerves had been 
cut was decidedly darker than the rest of the body. Similar results were once 
obtained from the division of the sciatic nerve in the thigh. When the opera- 
tion was performed, viz. at 45 30™ p.m. on April 4, 1857, the pigment was in 


1 The part of the paper devoted to this branch of the subject has been entirely rewritten ; and 
the dates in the text imply that most of the observations with reference to it have been made since 
the reading of the manuscript before the Society. 

* Vide Miller’s Archiv, loc. cit., p. 56. 


58 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


the stellate condition in the webs, the tint of the skin being moderately dark ; 
and this state of things continued unchanged in both limbs for the next six 
hours. On the following day, however, the leg operated on was seen to be very 
dark, and the pigment in its webs was reticular ; while in the rest of the body the 
colour remained as before, and the pigment was still stellate. This striking 
contrast continued unaltered for two days, when it was destroyed by the body 
generally assuming the darkest possible tint. 

The diffusion of the pigment in consequence of division of nerves appeared 
to be the counterpart of the concentration by their irritation, and it seemed 
probable that the want of constancy in the results in the former case was 
caused, like the variable amount and duration of arterial dilatation after such 
operations,’ by the place of the divided trunks being supplied by other branches ; 
and that, if the nerves of a limb were all completely severed, diffusion would 
necessarily take place. With the view of testing the truth of this idea, the 
following experiment was performed. In the afternoon of October 10, 1857, 
I divided in a pale frog all the soft parts in the middle of the right thigh, except 
the femoral artery and vein and the sciatic nerve; and late in the evening, 
having ascertained that the circulation was going on freely in the webs, I cut 
the nerve also, no effect having been hitherto produced upon the colour of the 
limb. Next morning the body generally was still pale, but the right leg was 
black from the wound downwards. The same remarkable appearance con- 
tinued till the evening, when circulation ceased in the limb. On the 13th I per- 
formed the same experiment upon both thighs of another large pale frog, leaving 
the sciatic trunks entire in the first instance, until I had ascertained that the 
circulation in the feet had not been interfered with. Three hours after this 
had been done I divided the nerve in the left thigh, and in about forty minutes 
observed that the leg was decidedly darker below the seat of operation. After 
another hour I found the pigment stellate in the left webs, whereas it was in 
the dotted condition in the right foot. J then cut the nerve in the right limb, 
and within a quarter of an hour the leg was already considerably darker below 
the wound, and the pigment in the webs had become stellate. Next morning 
the body was still pale, but the legs were very dark, and they continued to 
deepen in tint, although the animal was kept in a white earthen jar covered 
with glass in a bright light, till at about 3 p.m. they were almost absolutely 
black, while the pigment was diffused in the webs to the extremest degree, 
the body meanwhile and the upper parts of the thighs retaining their former 
light colour. The tint of the legs remained unaltered till the death of the animal, 
which took place several hours later. 


Ts See) Di Sil. 


ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 59 


The natural interpretation of these results appeared to be, that there 
exists a constant tendency to diffusion of the pigment in a limb so soon as it 
is liberated from the influence of the usually recognized nervous centres. It 
afterwards occurred to me, that if this were really true, diffusion of the pig- 
ment might, by proper management, be observed in an amputated limb before 
the supervention of the tendency to post mortem concentration: for I knew, 
from reasons to be mentioned hereafter, that this effect of death depended 
on the cessation of the flow of blood through the vessels, and, from what 
I had seen of arterial contractions in the frog’s web, and vermicular move- 
ments of the mammalian intestine from a similar cause, I felt sure that, if the 
blood were retained within the vessels, the arrest of the circulation could not 
be instantaneous in its effects upon the pigment, but that some minutes would 
probably be required to develop them ; during which time the diffusion result- 
ing from liberation of the pigment-cells from the influence of the ganglia in the 
trunk would proceed unchecked. Accordingly, on September 3, 1858, having 
tied a string tightly round the ankle of a pale frog, I immediately amputated 
above the ligature, and, avoiding the loss of time involved in tying out the toes, 
placed the foot at once on a plate of glass with a drop of water, two adjacent 
toes being kept apart by morsels of moistened lint. Within a minute and 
a half of the application of the string, the pigment in the web was observed 
to be in the angular condition, with short simple projecting processes, 1.e. 
approaching stellate, and two minutes later two contiguous cells were sketched 
in that state. About a minute after this it was evident that diffusion was 
taking place, and it continued to develop itself during the next ten minutes, 
at the end of which time the rays of the stellate pigment had shot out com- 
plicated offsets. Within the following five minutes, however, it was arrested 
by post mortem concentration, which gradually carried the pigment back 
to the angular state. This experiment, therefore, furnished confirmation of 
the view, that, in the ordinary circumstances of the animal, the influence of the 
central organs of the nervous system is required for the maintenance as well as 
the development of concentration of the pigment in the limbs. 

Supposing this to be established, it would follow that the accommodation 
of the tint of the skin to that of surrounding objects is certainly not the result 
of direct action of the rays of light upon the pigment-cells, but a reflex pheno- 
menon ; and it was an interesting question whether the afferent nerves concerned 
were the optic pair, or branches in the skin sensitive to luminous impressions. 
With a view to determining this point, I completely removed the eyes of a pale 
frog on September 13, 1858, at I p.m., and then placed it in a dark cupboard. 
During the first hour after the operation it became even paler than before, 


60 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


no doubt in consequence of the injury which had been inflicted, assuming 
apparently the lightest possible shade; and this continued with very little 
change till night, although the animal was still kept in the dark. Next morn- 
ing it was decidedly darker, and the tint was still deeper at 24 25" p.m. The 
glass containing the frog was now placed in a bright light, and surrounded on 
all sides by white objects ; but this change produced no difference in the colour 
of the skin, which continued till 7 30™ p.m. of a peculiar dingy hue. It was 
then put back into the dark place, and at 11" 4o™ p.m. was still exactly the 
same. On the following day, at 8a.m., the animal seemed a little paler, and 
was even lighter at 10 a.m., though still in the dark; so that it was evident 
that no difference whatever was produced upon its colour by admission or . 
exclusion of light. But that the nervous system generally was in a state quite 
disposed for acting upon the pigment-cells when subjected to appropriate 
irritation, was shown by the following circumstances. At the hour last men- 
tioned, the animal, having escaped from the vessel in which it was contained, 
struggled violently during my attempts to secure it, and in the short time thus 
occupied changed to almost the palest possible tint. It was then placed at once 
in the bright light, as before, but, in spite of this, was within ten minutes 
already decidedly darker, and, half an hour later, was almost coal black, though 
still subject to the full influence of white light. Just after this observation 
was made, the frog again escaped, and having again struggled considerably 
before it was replaced in the glass, it was seen to be within four minutes as 
pale as when first observed in the morning, but after the lapse of another 
half hour it was again almost as dark as ever, and continued so till 
2h 30" p.m., though all the while exposed to the same light. The observa- 
tions were continued for two more days, during which period the same 
complete indifference to the brightness or obscurity of surrounding objects 
was still evinced. 

These facts indicated pretty clearly that the eyes are the only channels 
through which the rays of light gain access to the nervous system so as to induce 
changes of colour in the skin. But for the sake of confirmation I thought it 
worth while to perform the following experiment. Two very dark frogs having 
been obtained, I put a hood of black cloth on the head of one of them, leaving 
the body and limbs uncovered, an aperture being made in the cloth below the 
throat for the purposes of respiration, and then placed them both in the same 
glass vessel exposed to white light. The struggles of the animal while the 
covering was being adapted and secured had the effect of making it grow 
much paler, so that it was of about medium tint when introduced into the 


* Probably from the irritation of the optic nerves. 


ON’ THE, CUTANEOUS PIGMENTARY SYSTEM OF THE FROG ‘62 


glass; while the other, which was from the first the darker of the two, still 
retained its original coal-black appearance. Half an hour after this had been 
done, the contrast between them was much diminished, partly in consequence 
of the dark one having become slightly paler, but much more from the paler 
having grown darker. After another half hour they were of precisely the same 
colour, and when another similar period had elapsed, that which was the darker 
to begin with was distinctly the paler of the two, being much lighter than at 
first, though still considerably darker than medium. A hood was now placed 
upon this animal, and that upon the other was removed, and both were replaced 
in the same light as before. This procedure occupied about ten minutes, and 
within seven minutes of its completion the creature which had the head un- 
covered was already the paler of the two, having grown decidedly lighter in 
colour ; while that on which the cap had been last placed seemed somewhat 
darker; and after another hour, while the latter was still of much the same 
dark shade, the former, with the head exposed, was very much paler, being about 
midway between the medium and the palest possible tint. An experiment 
of the same kind was performed upon another pair of frogs with very similar 
results, the details of which it is not necessary to mention. I afterwards found 
that the presence of the hood tends to check diffusion, or even in some cases 
to give rise to concentration of the pigment, probably by making the animal 
struggle to throw it off ; so that in one instance a frog which was put in a per- 
fectly dark place, immediately after the cap had been put on, grew much paler 
in the course of two hours. This circumstance prevents the skin from becom- 
ing as dark on the application of the hood as it would do if the head could be 
covered without exciting the animal. This, however, only renders the facts 
above mentioned more striking, so that they afford of themselves sufficient 
proof that the direct action of light upon the integument is incapable of affecting 
the pigmentary functions ; and thus the conclusion before arrived at receives 
complete confirmation from these experiments. 

There is of course nothing new in the fact that other functions besides 
vision may be excited in a reflex manner through the optic nerves ; the con- 
traction of the pupil, and the sneezing experienced by many persons on coming 
suddenly into bright sunshine, being well-known examples of such pheno- 
mena. On the other hand, the view that the cutaneous nerves are sensitive 
to luminous impressions was destitute of any support from analogy.’ 


1 In the chameleon, a part exposed to the sun becomes dark, while the rest of the body remains 
unaffected. I have little doubt, however, that this is due to the calorific, not the luminous rays. That 
heat does produce such an effect was lately demonstrated to me by Professor Goodsir upon a living 
chameleon, which, when held in broad daylight before a dull-red fire for a short time, grew much darker 
on the side that was warmed, but retained elsewhere its former pale green colour. 


62 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


From the part taken by the second pair of nerves in bringing about the 
changes in the tint of the skin under the influence of light, and also from the 
darkening of the hind legs observed to occur after dividing within the canal the 
roots of the branches which supply them,' we learn that the cerebro-spinal axis 
is chiefly, if not exclusively, concerned in regulating the functions of the pig- 
ment-cells. Considering that those functions have probably a close affinity 
with the processes of secretion and nutrition, it is interesting to find that they 
are thus subject to the control of the spinal system. 

The circumstance before alluded to, that a dark frog always becomes pale 
after death, is mentioned both by von Wittich and Harless, but without any 
discussion of its cause. This post mortem concentration takes place in a limb 
in spite of amputation, and therefore cannot be due to the agency of any ganglia 
contained in the head or trunk. Neither can it be the result of failure in action 
on the part of such ganglia; for if the circulation be artificially arrested in 
a part of a living frog without interfering with the nerves leading to it, a similar 
change in the pigment to that which results from death comes on before the 
nerves have become, so far as we can judge, at all impaired in their functions. 
This was proved by the following experiment :—On June 7, 1858, having tied 
the right femoral artery of a moderately dark frog in the middle of its course, 
I divided it below the ligature, and also cut through, in the same situation, all 
the soft parts of the thigh except the sciatic nerve with a little adherent muscle. 
The operation was completed at noon, when the animal was put into a dark 
place; and at 1! 4om p.m. the body generally was darker, but the right leg 
from the wound downwards was decidedly paler than before; the animal, 
however, still moved it freely. At 64 20m p.m. the general surface was as dark 
as ever, but the right foot presented the extreme degree of pallor; yet the 
creature still moved the leg both spontaneously and when the toes were 
pinched, showing that the motor and sensor nerves retained their functions. 
Sensation, however, was not so acute as in the left foot ; in the latter a touch 
sufficed to induce movements in the body generally, whereas in the former 
a pinch was necessary to produce the same effect. At Io! 15™ p.m. the same 
contrast in colour continued, but no movement could be induced in any manner 
in the pale limb, although obscure indications of a certain amount of sensibility 
remaining in it were still elicited by forcible pinching. 

In this case, concentration of the pigment came on in the limb in con- 
sequence of arrest of the circulation through it, several hours before its nerves 
concerned in sensation and motion had lost their powers, and therefore at 
a time when we cannot doubt that the ganglia in the trunk had full opportunity 


eee Puy, 


ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 63 


for acting on the pigment-cells, which, as we know from experiments before 
mentioned, are capable of being influenced through the sciatic trunk. Hence 
it appears that post mortem concentration is the result of the cessation of the 
flow of the blood through the vessels, and that it is a purely local phenomenon 
developed in some manner quite independent of the central organs of the 
nervous system. 

The period at which it occurs varies a good deal in different cases. This 
seems to depend partly upon whether the blood is retained in the vessels or not. 
Thus in one instance in which a piece of web was cut out, so as to ensure com- 
plete escape of the vital fluid, the process was already considerably advanced 
within nine minutes ; whereas in the case above related, in which the blood was 
retained in the limb by a ligature, concentration did not commence till full 
a quarter of an hour after amputation. The season of the year also seems to 
have a great effect. In a cold room, in the depth of winter, I have known 
some hours elapse before the pigment began to change in an amputated limb : 
this is probably owing to greater languor in all the vital processes during the 
period in which the creature naturally hibernates. 

The dead frog, if previously healthy, assumes after a while a nearly uniform 
pale colour, concentration being carried to the extreme degree in all parts. 
It does not, however, remain in this condition; for when a variable time has 
passed, the skin becomes again somewhat darker, and on microscopic examination 
the pigment is found pretty uniformly angular or stellate. Nor are these the 
only changes to which the pigment is liable after death, as I first became aware 
in April 1858, when examining an amputated limb with reference to the post 
mortem contractions of the arteries, the blood being retained in the vessels. 
In that case, after complete concentration followed by slight diffusion had taken 
place, irregular changes began to appear ; some tracts of the web under observa- 
tion becoming affected with more or less full diffusion of the pigment, while 
in others it became more concentrated. Then after the lapse of some hours 
its state was found reversed, being concentrated in parts where it had been 
diffused, and vice versa. These curious variations continued till so late 
as the tenth day after amputation, becoming more frequent after the first 
few days; so that sometimes a considerable alteration was observable within 
half an hour. 

These facts appeared to me of great importance, as proving the con- 
tinuance of vital actions for a much longer time than had been previously 
supposed possible in a severed portion of the body. They seem also valuable 
with reference to the influence of the nervous system over the pigmentary 
functions ; for the circumstance that considerable patches of the web usually 


64 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


had the pigment in the same condition throughout at one time implies that 
a large number of pigment-cells were acting in concert, and therefore probably 
under the control of the nervous system, although, as the leg had been amputated, 
they were of course freed from the influence of the central ganglia. Hence 
we are led to suspect the existence in the limb of an apparatus, probably gan- 
glionic in structure, co-ordinating the actions of the pigment-cells, just as we 
know that the muscular contractions in the mammalian intestine are harmonized 
by a local mechanism of that nature, while we have reason to think that the 
same thing holds regarding the arteries in the frog’s web.’ Such a view is in 
accordance with the results of recent anatomical discovery, which has revealed 
nerve-cells in many parts where their occurrence had not previously been con- 
jectured. But in the absence of more positive evidence, we must be careful not 
to trust too much to analogy on such a point; for it by no means necessarily 
follows, that, even if muscular fibre-cells are incapable of acting in mutual 
harmony without the aid of the nervous system, the same must be the case 
with pigment-cells, which, it is to be remarked, resemble ganglion corpuscles 
in being connected together by anatomosing offsets. The nerve-cells, if such 
be really the means by which the harmonious actions of the pigment-cells in 
an amputated limb are induced, must be disseminated among the tissues of the 
web itself ; for both post mortem concentration and secondary diffusion occur 
in a piece of web cut out and placed in a drop of water on a plate of glass. 
This was ascertained on September 4, 1858, in the case already alluded to as 
an instance of rapid occurrence of concentration. About half an hour after 
removal from the body, the pigment, previously reticular, was in the dotted 
state, and three hours later it was found to be again stellate. 

The case of the pigment-cells 1s analogous to that of the arteries in this 
respect, that, so long as circulation is going on, they are generally in entire 
subjection to the central ganglia, and act only when stimulated by their in- 
fluence. But as, in the arteries, it appears to be by the independent action 
of the local nerves that a contraction caused by direct irritation spreads to: 
a considerable distance from the part operated on, so it is probably by local 
means that the pallor induced by pinching the web affects a circle of surrounding 
tissue. If this be true, the case of direct irritation will be an exception to the 
general rule, that, while circulation continues healthy, concentration always 
implies the operation of the central organs of the nervous system. 

Comparing the changes in the pigment in an amputated limb with those 
which take place under similar circumstances in the arteries,” it appears that 


* See the preceding paper ‘On the Parts of the Nervous System which regulate the Contractions. 
pr therArtertes” sp: Ar: * See the preceding paper before referred to, p. 39. 


ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 65 


the first effect of removal from the influence of the nervous centres in the head 
and trunk is arterial relaxation and pigmentary diffusion, followed in a variable 
time by contraction of the vessels and concentration of the dark molecules, 
giving place again to relaxation and diffusion, after which succeed irregular 
alternations of contraction and dilatation in the one case, and of concentration 
and diffusion in the other. Here, though the vascular and pigmentary changes 
do not at all correspond with one another in point of time, yet there is an evident 
parallel between them; and, admitting that in each case the variations are 
the result of alternate action and inaction of the appropriate local nervous 
system, it is evident that concentration of the pigment corresponds to contrac- 
tion of the muscular fibres of the arteries ; these being both the results of nervous 
action, while diffusion of the pigment, like arterial relaxation, takes place when 
the nerves cease to operate. It will be remembered that a similar conclusion 
was derived from the study of the influence exerted upon the pigment-cells by 
the central ganglia. Hence it appears that the tendency to diffusion of the 
pigment-molecules is in constant operation in the cells, but kept in check by an 
antagonistic concentrating agency varying in obedience to nervous influence. 

It is an interesting circumstance, that two functions seemingly so totally 
distinct as muscular contraction and pigmentary concentration, should both be 
thrown into a state of activity in consequence of arrest of the circulation. It 
is to be remembered, however, that there is no evidence that either the in- 
voluntary muscular fibre or the pigmentary tissue is directly influenced by 
the cessation of the flow of blood, the effect being apparently produced through 
the medium of the local nervous system. This we know with certainty in the 
case of the post mortem movements of the intestines ; and we have seen reason 
to think it likely that the same is true regarding the contractions of the arteries 
after death, and the concentration of the pigment under similar circumstances. 
It is a curious question how the arrest of the circulation causes these actions 
of the local nerves. The idea suggested by the facts is that the tissues begin 
to suffer from the want of fresh supplies of the vital fluid, and resent the injury, 
as it were, by a struggle. 

Rich in results of general physiological interest as the study of the pig- 
mentary system of the frog has proved, it has yielded fruit of not less value 
in a pathological point of view. Indeed, what induced me to investigate the 
functions of concentration and diffusion, was the unexpected light thrown 
upon the nature of inflammation by the effects produced by irritants upon 
those processes. For information on this subject I beg to refer the reader to 
my paper “On the Early Stages of Inflammation ’.’ 


1 See p. 209 of this volume. 
LISTER I F 


66 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


The pigmentary system also promises to render good service in toxological 
inquiry. Hitherto, in experiments performed upon animals with that object, 
attention has been directed chiefly, 1f not exclusively, to the effects produced 
upon the actions of the nervous centres, the nerves and the muscles. In the 
pigment-cells we have a form of tissue with entirely new functions, which, though 
apparently allied to the most recondite processes of the animal economy, yet 
produce very obvious effects, and thus afford great facilities for ascertaining 
whether or not they have been destroyed by any poison that may have been 
administered. 

An experiment of this kind which I once performed, though with a different 
object, may be mentioned by way of example. Being desirous of confirming 
the conclusion to which I had been led by experiments above related, viz. 
that diffusion always tends to take place when the influence of the nerves is 
withdrawn from the pigment-cells, it occurred to me that the urari poison 
might be brought into requisition for that purpose: for it has been shown by 
Professor Kolliker of Wirzburg, that this substance paralyses in the first 
instance the extremities of the motor nerves without affecting the contractility 
of the muscular tissue; and supposing the nerves concerned in regulating 
the pigmentary changes to be similarly deprived of their powers, while the 
pigment-cells themselves remained intact, diffusion should take place after 
exhibition of the drug, provided my view were correct. Accordingly, at 
2 tom p.m. on December 21, 1857, I introduced beneath the skin of the back 
of a pale frog a portion’‘of urari extract, for which I was indebted to the kindness 
of Dr. Christison. At 2! 25™ reflex action was entirely abolished, the creature 
being to all appearance dead, so far as could be judged by the naked eye, 
although the microscope showed that circulation continued in the webs. The 
pigment meanwhile had become stellate, but did not continue in that con- 
dition, being, half an hour later, found fully concentrated. Soon after this, 
however, diffusion again commenced, and continued to advance steadily till 
circulation ceased early the following morning, at which time the integument 
was almost black. In the course of a few hours, however, it was brought again 
back to the palest possible tint by post mortem concentration. 

The diffusion which ultimately took place in this case was no doubt due 
to loss of function on the part of the central ganglia or the nerves connecting 
them with the pigment-cells. But from the occurrence of concentration half 
an hour after the faculty for reflex action had ceased, we learn that these nerves, 
like the intrinsic motor nerves of the heart and intestines, remain unaffected 
by the urari poison for a considerably longer time than those which excite the 
contractions of the voluntary muscles. We further learn from the fact that 


ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 67 


post mortem concentration came on as usual, that the pigment-cells retain 
their powers, and also their capability of acting in mutual harmony after the 
rhythmical contractions of the heart have been abolished by this poison. 

Such experiments are so readily performed, and the effects produced upon 
the pigment-cells or the nerves which govern them are so obviously indicated 
by the changes of colour in the integument, that I venture to recommend this 
method of investigation to those who are occupied in studying the action of 
poisons. 


68 ON THE CUTANEOUS PIGMENTARY SYSTEM OF THE FROG 


PATE, Ti 
illustrates the anatomy and physiology of the cutaneous pigmentary system of the frog. 


Figs. 1 and 2 are sketched from webs of different feet of the same animal. The creature was dark when 
it was killed, but one of the legs afterwards underwent the usual post mortem change to a pale 
colour, and such was its state when Fig. 2 wasdrawn. The other limb was deprived of the power 
of thus altering by immersion for half a minute in chloroform ; and Fig. 1 shows the appearance 
of the colouring matter in the permanently dark condition of the integument. 


ty 
gq 


. 3 represents two chromatophorous cells with the pigment-granules fully diffused, the animal having 
been at the time coal-black. The bodies of the cells are seen to be pale, containing chiefly colour- 
less fluid, while some of the finest branches of the offsets are quite black, in consequence of the 
dark molecules being closely packed together in them. In the same figure a capillary fully 
distended with blood-corpuscles is also given. 


Fig. 4 represents the colouring matter in the same two cells during the progress of the process of con- 
centration. The dark molecules are already for the most part collected about the middle of 
the body of each cell; but in the very centre of each cell is a pale point, where the granules seem 
not yet to have insinuated themselves between the cell-wall and the nucleus. The same capillary 
is here seen much reduced in calibre. 


Fig. 5 shows the pigment in the lower of the two cells, concentration being still further advanced. 


In Fig. 6 the process is seen to be almost absolutely completed, the molecules being almost all of them 
aggregated into a black circular mass, occupying the middle of the body of the cell, the more 
circumferential parts of which contain only colourless fluid, and are therefore invisible. 


Fig. 7 is an outline of the wall of a large blood-vessel, with chromatophorous cells in its external coat. 
The pigment is almost completely concentrated, but the form of the section of the black masses, 
where they are seen edgewise, shows that they are not spherical, but disc-shaped. 


Figs. 8, 9, and 10 are drawn, with a much higher power, from young frogs, with small pigment-cells : 
they exhibit especially the form and relations of the nucleus. 


In Fig. 10 the pigment is shown in an unhealthy state, the molecules being irregularly aggregated. 


—_ eS WY At 


| = a 


oNareae 


Bee 
De a 


500 diam s 


ON SPONTANEOUS GANGRENE FROM ARTERITIS 
AND THE CAUSES OF COAGULATION OF THE 
BLOOD IN DISEASES OF THE BLOOD.VESSELS 


Read before the Medico-Chirurgical Society of Edinburgh, March 17, 1858. 


[Edinburgh Medical Journal, April 1858.] 


Mr. PRESIDENT AND GENTLEMEN.—The case which I have the honour 
to bring before you this evening is one of spontaneous gangrene in a child. 
The patient was a girl, six years old, who, having had scarlet fever nine months 
previously, and afterwards suffered severely from dropsy, was seized about the 
middle of July last with deadly whiteness and coldness of both lower limbs up 
to a little above the knees. Her mother describes them as having resembled 
wax In appearance. She and her neighbours rubbed the legs perseveringly, 
and, after an hour or two, the left limb recovered its warmth and usual aspect, 
but the other continued in the same state for about two days, when the mother 
observed some pale blue discoloration between the ankle and the calf. This 
increased, spreading downwards to the foot; and, at the same time, under- 
going various changes of tint to pink, red, and green, till, at the end of four 
weeks, the limb presented the appearance depicted in this sketch. [Not here 
reproduced.| At this time she was brought to the Royal Infirmary, and was 
admitted into one of the senior surgeon’s wards, where, in the temporary absence 
of Mr. Spence, she came under my care. Her general health appeared remark- 
ably good, considering all that she had gone through: her tongue was clean 
and moist, and her appetite good, and though her pulse was very quick, viz. 
148, this was not to be regarded as a serious symptom in one so young, with 
such a source of irritation present. Accordingly, three days later, a line of 
demarcation having distinctly declared itself, I performed amputation im- 
mediately above the knee. Very little blood was lost in the operation, which 
did not accelerate the pulse or impair the appetite even for a day. Three days 
later, the constitution was evidently experiencing relief from the removal of 
the disease: the pulse was reduced to 112, and her general aspect improved. 
The stump healed kindly, and the result was in all respects satisfactory. 

The amputated limb having been laid open on its posterior aspect, the 
gangrene was found to have extended somewhat higher in the deep parts than 


70 ON SPONTANEOUS GANGRENE FROM ARTERITIS AND 


in the skin; the mortified tissues, including the posterior tibial nerve, were 
congested in a manner closely simulating inflammation, but of a duller tint, 
and exactly as far as this congestion extended, the posterior tibial venae comites 
were turgid, and evidently contained coagulated blood. In the upper part of 
the limb the veins were flaccid and empty, and all the tissues appeared healthy, 
except that the popliteal artery, for an inch and a half from its lower end, was 
the seat of intense congestion, which also implicated slightly the cellular tissue 
about the vein and nerve. [These appearances were represented in a coloured 
drawing.| On laying open the vessels, the vein was found pervious and healthy, 
except that its coats seemed a little thicker than natural, but the artery was 
filled at the congested part with a coagulum, an inch and a quarter in length, 
partly pinkish and partly dark in colour. There was no appearance of any 
inflammatory exudation having taken place into the interior of the vessel, 
but the clot lay everywhere in contact with the internal coat, to which it was 
firmly adherent, so much so, as to tear away a portion of it when removed. 
Beneath the lining membrane were to be seen transverse red streaks, which 
appeared due to congestion of the circular coat of the vessel. [A sketch of the 
vessel and its contained clot was now exhibited.} The coagulum extended 
down the anterior tibial artery as far as to the commencement of the gangrene, 
but the companion veins were empty and perfectly natural in appearance, as 
also was the posterior tibial artery. 

These pathological appearances clearly indicate that the primary disease 
was inflammation of the arteries, accompanied by coagulation of the blood 
within them, obstructing the supply of the nutrient fluid, and so inducing 
death of the lower part of the limb. This conclusion is in harmony with the 
previous history, which was from the first that of arterial obstruction. 

This case is of practical interest, as illustrating the principle that spontaneous 
gangrene may be entirely local in its cause, and that in such cases the greatest 
benefit may be anticipated from removal of the mortified part, provided the 
constitution be in a state fitted, as regards age and in other respects, for bearing 
the operation. 

But my chief reason for bringing the case now before the Society is because 
it appears a distinct example of inflammation of the coats of a vessel determin- 
ing coagulation of the blood within it, without the exudation of lymph into its 
interior. Not that there is any novelty connected with such an occurrence, 
but because this effect of arteritis and phlebitis, long recognized by all sound 
pathologists, appears to be of peculiar interest at the present juncture, in con- 
nexion with the recent publication of the last Astley Cooper Prize Essay, in 
which Dr. Richardson of London propounds the theory, that the coagulation 


THE CAUSES Or COAGUEATION OF THE BLOOD Wek 


of the blood is due to the escape of a minute quantity of ammonia, which he 
believes holds the fibrine in solution. I propose, therefore, on the present 
occasion, to consider how far this new theory accounts for this phenomenon 
of coagulation in inflammation and other diseases of the blood-vessels. 

So short a time having elapsed since the publication of the volume alluded 
to, it may be well to mention, as briefly as possible, the main facts by which 
the arguments of the author are supported :—And first I may relate the startling 
observation made by Dr. Richardson, that if a current of air is passed through 
two successive portions of freshly drawn blood, contained in two Wolfe’s bottles, 
while that in the first bottle, as might have been expected, has its coagulation 
accelerated, that in the second bottle is prevented from coagulating for several 
minutes after the time at which it would have solidified, had it been left in the 
vessel without interference. In other words, the air has had its properties so 
modified in passing through the first mass of blood, that it afterwards retards 
instead of promoting coagulation; whence Dr. Richardson infers, that it 
has obtained in its passage some volatile solvent of the fibrine. Secondly, 
Dr. Richardson has discovered that a very minute quantity of ammonia added 
to freshly drawn blood keeps it fluid for an indefinite period in a stoppered 
bottle, but that if exposed to air it coagulates as usual, though at a later period, 
in proportion to the amount of ammonia employed. He also finds that, by 
careful management, a fresh clot may be redissolved by means of ammonia, 
and that after the escape of the ammonia it will again coagulate, and afterwards 
contract in the usual manner, though more feebly. Next, he finds that ammonia 
is always to be obtained from the halitus of freshly drawn blood, and although 
the alkalinity of the blood through soda renders the ammonia excessively 
prone to escape, so that a good deal is necessarily lost from unavoidable ex- 
posure to air, yet he has succeeded in collecting about a third by weight of 
the smallest amount which he has found sufficient to keep the blood per- 
manently fluid outside the body. Lastly, he has observed that all those 
circumstances which are known to promote the coagulation of blood outside the 
body, such as an elevated temperature, free admixture with air, a vacuum, X&c., 
also hasten the process in blood mixed with ammonia, or, in other words, 
favour the escape of the volatile alkali; while, on the other hand, those things 
which check coagulation, such as cold and occlusion from air, prevent or retard 
the evolution of the gas. To the latter class he has added the remarkable fact 
that blood remains fluid for many hours under a high mercurial pressure, but 
coagulates when relieved from it. I confess that, although I was by no means 
prepossessed in favour of this theory, these facts appear to me to prove irre- 
sistibly that the cause of the fluidity of blood, after it has been drawn from the 


72 ON SPONTANEOUS GANGRENE FROM ARTERITIS AND 


body, is a minute portion of free ammonia holding the fibrine chemically in 
solution, and that the coagulation of such blood is the result of the escape of the 
alkali. The only point on which the evidence appeared deficient was the effect 
of occlusion from air in tubes of dead matter, and this defect I endeavoured 
to supply by the experiment which I mentioned at the last meeting of the 
Society, by which I succeeded in keeping the blood of a sheep fluid for three 
hours within a vulcanized india-rubber tube, the blood coagulating in about 
two minutes when let out just as if freshly drawn from the veins of the 
animal.' Hence it appears to me that the medical profession is deeply indebted 
to Dr. Richardson for his laborious and able investigations, which have, as 
I think, removed much mystery from this long vexed question. 

But Dr. Richardson aims at much more than the explanation of coagulation 
outside the body. He believes that the fluidity of the blood within the healthy 
living vessels is due simply and solely to the presence of free ammonia, which he 
supposes to be generated either in the systemic or pulmonary capillaries, and 
he denies that the walls of the arteries or veins have any effect on the blood 
by virtue of their vitality, or exercise any other influence upon it than that of 
checking the evolution of ammonia, just as would be the case were they tubes 
of dead matter of the same degree of permeability. And all cases of coagulation 
within the living body are supposed, by him, to be explicable on simple chemical 
principles. Here, however, I find myself quite unable to follow him. Thus, 
he believes that the coagulation in an aneurysm is the result of the blood which 
is at rest in the tumour giving up its ammonia to the current which is flowing 
past the mouth of the sac. This theory was suggested to him by the following 
circumstance :—In one of the experiments of transmitting air through suc- 
cessive portions of blood, the longer tube in the last Wolfe’s bottle was 

* This experiment was performed in the following manner :—One of the jugular veins of a sheep 
having been exposed, it was emptied of blood by passing the finger along it while pressure was applied 
by an assistant at its anterior part. The vessel was then opened at two places about three inches distant 
from each other, and into each opening was tied one end of a piece of vulcanized india-rubber tube, 
a quarter of an inch in diameter, and about eighteen inches long, filled with water, to prevent the intro- 
duction of air into the circulation. The pressure was then removed from the upper part of the vein, 
so as to allow the blood to flow through the tube. It was now easy to ascertain, by observing the col- 
lapse of the lower part of the vein, when a part of the tube was momentarily obstructed by pressure, 
that the circulation was going on freely through the new channel. This having been determined, 
ligatures of waxed string were tied as tightly as possible round the tube, at intervals of about two 
inches, beginning at the end next the head and proceeding backwards, so as to avoid all tension upon 
the enclosed blood, which was, of course, displaced freely in the direction towards the thorax. By 
this means a number of portions of blood were obtained enclosed in receptacles nearly, though not 
absolutely, impermeable to gases. The various compartments were opened at different intervals, and up 
to three hours some of them contained fluid blood which coagulated on exposure, whereas there was 
in others a considerable portion of coagulum. After four hours, coagulation was almost complete, 


but a slender thread of fibrine was still obtained from the fluid part in one of the divisions a few minutes 
after it had been let out. 


THE CAUSES OF COAGULATION OF THE BLOOD 7 


accidentally too short, so that it did not reach farther down than to about an 
inch from the bottom of the vessel. The result was, that while the upper part 
of the blood in this last bottle was retained fluid for a considerable time, that 
below the level to which the tube reached speedily coagulated. Dr. Richardson 
infers that the lower portion of blood gave up its ammonia to the air which 
was bubbling through the upper part sufficiently charged with the alkali to 
retain that part in a state of fluidity. But, surely, this implies a mistake in 
chemistry. The lower portion of blood coagulated, I imagine, for the same 
reasons that it would have done had it been put in a stoppered bottle’ after 
passing through the air, though probably not quite so rapidly, while the other 
part was prevented from coagulating by the ammoniacal vapour bubbling 
through it. 

But if the ammonia theory fails to explain the coagulation that occurs 
in aneurysm, still more inadequate does it appear to account for the phenomenon 
in arteritis or phlebitis. How can the fact that the wall of the vessel is 
inflamed determine, on simply chemical principles, the evolution of ammonia 
from the blood within it? Being convinced that in these and other cases of 
coagulation of the blood in local diseases of the vessels something remained 
quite unexplained, I have, during the last fortnight, made several experiments, 
with a view to throwing further light upon the subject, and will now com- 
municate to the Society the results at which I have arrived. 

In reflecting upon the matter, some circumstances in physiology and 
pathology appeared to me to indicate that, on the hypothesis that the blood 
does contain free ammonia in the living body, the healthy vessels must have 
a special power of preventing its escape. Thus, the blood in the capillaries of 
the lungs is separated from the air in the air-cells only by an excessively thin 
partition of permeable living tissue; yet Dr. Richardson’s experiments have 
shown that there are times in the day, as, for instance, early morning, in which 
not a trace of ammonia is given off in the breath. Again, in surgical emphysema, 
the tissues of the body may be enormously distended with air, without any special 
tendency to coagulation of the blood in the vessels, such as might be antici- 
pated unless their parietes have a special power of preventing the escape of 
ammonia. It is true that in this case, the blood being in constant circulation, 
a perpetual supply of lost ammonia might be maintained from the capillaries ; 
but it occurred to me that some information might perhaps be gained upon 
the point in question, by producing emphysema artificially in a limb in which 
the circulation had been arrested. For this purpose I applied a tourniquet 
firmly to one of the fore legs of a sheep, just above the elbow, and then injected 


+ This occurrence I have frequently observed.—J. L. 


74 ON SPONTANEOUS GANGRENE FROM ARTERITIS AND 


air, by means of a condensing syringe, into the tissues of the lower part of the 
limb. The struggling of the animal, however, caused repeated displacement 
of the tourniquet, which I did not succeed in retaining in position for longer 
than an hour at a time. But, though the experiment was so far a failure, it 
yielded fruit in an unexpected manner. Having amputated the limb and pre- 
served it, though with little expectation of learning anything from it, I was 
surprised to find, on examining it six hours later, that, although the cellular tissue 
about the vessels was still fully distended with air, the blood within them was 
perfectly fluid, and coagulated in about two and a half minutes, when shed 
into a saucer. Still greater was my surprise on finding next day, sixteen hours 
after the amputation, that the blood was still fluid in the vessels ; and though 
it took longer to coagulate when let out from them, viz. five minutes, did so as 
fully as before. The muscular irritability, as tested by a powerful galvanic 
battery, had been found, on the previous evening, to be entirely lost. I next 
obtained four other feet, with the veins turgid with blood, by applying bandages 
firmly to the limbs below the joints where the butcher removes them, and 
amputating above the constricting band, after the sheep had been killed in 
the usual manner, by the knife. I examined veins in these limbs, day after day, 
till all the vessels were exhausted, and found at the end of the sixth day after 
their severance from all connexion with the vascular and nervous centres, that 
the blood from a deep vein was still perfectly fluid, and coagulated when shed, 
though the time occupied by the process was now half an hour,—the length of 
the period having gradually increased, from day to day, since the time of the 
amputation. The feet, in the meantime, continued perfectly sweet, the coldness 
of the weather at the time being very favourable for the experiments. Some 
blood from a subcutaneous vein of the same foot, where decomposition might 
be expected to occur somewhat earlier, contained, at the same period (the end 
of the sixth day), some minute portions of coagulum. The fluid part of this 
blood remained liquid for an hour, but then coagulated well. Hence it was 
evident that so long as the tissues retained their freshness, the blood within 
the vessels was kept in a state of fluidity by some agency utterly inexplicable 
by the ammonia theory. I also found that the same thing occurs in the cat. 
In one such animal, killed under chloroform, by a knife passed into the great 
vessels of the neck, the blood in the veins of the extremities remained perfectly 
fluid after forty-eight hours, and coagulated when shed. In another cat, killed 
by asphyxia, the same was the case as regards the posterior extremities ; but 
the veins of the fore legs contained particles of coagulum, like the subcutaneous 
vessel of the sheep’s foot. This difference I am inclined to attribute to the 
fact that the animal made violent and protracted exertion with the fore legs 


THE CAUSES ,OR, COAGULATION OF THE BLOOD 75 


during the death struggle, thus exhausting their vital energies more than those 
of the other limbs. After four days, however, the blood in the hind legs, though 
still fluid, with the exception of very minute particles of coagulum, had lost 
its power of coagulation. This increasing slowness and final absence of coagula- 
tion in blood long kept within the vessels is curious, and must, I imagine, depend 
upon some gradual change in the properties of the fibrine. 

We have seen that in two classes of the higher animals, differing from one 
another as widely as the carnivora and herbivora, and after modes of death so 
various as haemorrhage, asphyxia, and an operation performed under chloroform, 
the blood remains fluid in the vessels, though perfectly at rest, for days after 
death. It may appear almost incredible that a fact of such fundamental im- 
portance, and at the same time so easy of demonstration, should have escaped 
the observation of all the eminent men who have made the coagulation of 
the blood a subject of special study; yet such appears to be the case. 
Dr. Richardson speaks of occasional instances of fluidity of the blood after 
death, and coagulation on exposure, but considers it quite essential for such 
an occurrence that the vascular system should not have been opened by wound, 
though it is difficult to see how such a circumstance could affect the question, 
according to his theory, except on the supposition that the blood-vessels were 
impermeable to gases in solution. Again, Dr. Davey, in his Researches, writes 
as follows :—‘ The blood, after death, I have often found liquid, and that many 
hours after death, when cold, but still retaining its power of coagulating’ ; 
but he had no idea of fluidity and coagulability lasting for days after death, or 
even for hours, except in rare instances. The nearest approach which I have been 
able to find to such an observation is contained in that inexhaustible treasury of 
original observation and profound reflection, the works of John Hunter, where 
the following passages occur :—‘ As a proof that blood will not coagulate in 
living vessels, in a perfect and natural state, and ready to act when powers 
were restored to it, I found that the blood of a fish, which had the actions of 
life stopped for three days, and was supposed to be dead, did not coagulate 
in the vessels, but, upon being exposed or extravasated, soon coagulated. 
. . . The blood of a lamprey-eel, which had been dead to appearance some days, 
was found fluid in the vessels, because the animal was not really dead: there 
had, however, been no motion in the blood, as the heart had ceased acting ; 
but upon its being exposed, or extravasated into water, it soon coagulated’ 
(Palmer’s edition, vol. iii, p. 32). Hunter, however, does not seem to have 
drawn any inference with regard to the higher animals from these cases. He 
speaks of ‘ the very speedy coagulation of the blood which usually takes place 
in all the vessels after death’ (vol. ili, p. 27); and though he believed that 


76 ON SPONTANEOUS GANGRENE FROM ARTERITIS AND 


“where there is a full power of life, the vessels are capable of keeping the blood 
in a fluid state’, he also supposed that some motion, though ‘ very little, is 
required to keep up its fluidity’ (ib., p. 32). Indeed, the expression, ‘ full 
power of life,’ just quoted, is quite inconsistent with the state of a sheep’s 
foot, six days after muscular irritability has been lost. I had myself frequently 
made experiments on inflammation upon the amputated limbs of frogs, and 
observed that the blood remains fluid for more than twenty-four hours after 
death ; but muscular irritability, ciliary action, &c., also last in those creatures 
to a very much later period than in the higher animals, so that I never ven- 
tured to infer that fluidity of the blood was likely to continue long after death 
in mammalia. 

Further observations on the feet of the sheep and limbs of the cat proved 
even still more strikingly the influence of the vessels upon their contained blood. 
If the skin be reflected from over a subcutaneous vein full of blood, and lightly 
replaced, so as to protect the subjacent parts from evaporation, without exclud- 
ing the air, the vessel will be found, in two or three hours, changed from a dark 
venous colour to a scarlet arterial tint; yet no coagulation will occur in the 
blood, although the oxygen of the atmosphere has evidently penetrated freely 
through the coats of the vessel, showing that abundant opportunity has 
occurred for evolution of ammonia, provided any tendency to such an occurrence 
existed. Again, if such a vein be cut across with fine sharp scissors, without 
disturbing its connexions, or inflicting much injury on its coats, the blood 
will be found, after about six hours, perfectly fluid in the vein, up to within 
perhaps 1-20th of an inch of the wound, where a small clot is perhaps seen, utterly 
insufficient to obstruct the progress of ammoniacal vapour. Hence it appears 
to me to follow, as a matter of demonstration, that, if free ammonia really 
exists in the blood within the vessels, the circumstance of its being in those 
vessels deprives it entirely of its volatility ; and that, whether the ammonia be 
free in the blood or not, its chemical tendencies, such as it exhibits outside the 
body, are in some manner entirely modified by the vicinity of the vascular tissue. 
With regard to the nature of the modifying influence, no other explanation 
appeared to offer itself than that it depended upon residual vitality in the tissues. 

In order to prosecute the investigation of the cause of coagulation in 
arteritis or phlebitis, I endeavoured to produce artificially, as nearly as practic- 
able, in a living animal, the condition in which the vessels are when inflamed. 
Having proved, as I think I may venture to say—by investigations, an account 
of which will shortly appear in the Philosophical Transactions 1—that inflamma- 
tion consists in an impairment of the vital energies of the tissues of the part 


* See p. 209 of this volume. 


TE CAUSES OF COAGULATION OF THE BLOOD Ta 


affected, I resolved to destroy the vitality of a vein, and then permit the blood 
to flow through it for some time, and ascertain whether coagulation would 
occur in spite of the current, as it must do in phlebitis... The agent which 
seemed best adapted for inflicting the lesion was strongest liquor ammoniae, 
both on account of its rapid action, and also from the circumstance that, as 
Dr. Richardson has shown, its chemical effect upon the blood, whether applied 
concentrated or diluted, is to prevent coagulation. On the 8th inst., having 
exposed one of the jugular veins of a sheep, and isolated it from surrounding 
connexions for six inches of its length, carefully avoiding even momentary 
obstruction of the flow through it, I placed a plate of glass beneath the vein, 
to protect the neighbouring tissues from the action of the alkali, and at 3! 13™ 
p.m. emptied the portion of vein of its blood, by stroking the finger along 
it, while an assistant exerted gentle pressure on the anterior part, and then at 
once applied the liquor ammoniae thoroughly, with a camel’s hair brush, to all 
sides of the vessel throughout the length exposed. The application of ammonia 
occupied three-quarters of a minute, and three-quarters of a minute later the 
blood was again allowed to flow through the vessel, having been arrested 
altogether a minute and three-quarters. A short time having been allowed 
for the evaporation of the ammonia, the edges of the wound were brought 
together with stitches. At 4» 58™, or an hour and three-quarters later, the 
wound having been opened, the flow was again obstructed as before, and the 
vein was rapidly sht up. A small amount of dark coagulum escaped with the 
fluid blood. The interior of the vessel was now immediately examined. A valve 
with three flaps, about the middle of the opened portion, was rendered con- 
spicuous from the fact that a black coagulum existed between each of the flaps 
and the wall of the vessel; and on careful observation of the lining membrane 
of the vein in other parts, it was seen to be dotted over in patches with fine 
granular deposits of pink fibrine, which could only be detached by firmly scrap- 
ing with the edge of the knife, reminding me precisely of the close adhesion 
of the clot which occurred in the popliteal artery in the case which I related 
at the commencement of this paper, and which is known to be characteristic 
both of arteritis and phlebitis. Here it is clear that the coats of the vessel 
having been deprived of their vitality, the blood flowing through it assumed 


* Sir Astley Cooper performed experiments to show the effect of mechanical injury of the coats 
of a vein upon the coagulation of the blood at rest within a portion of the vessel contained between 
two ligatures; and he came to the general conclusion, that loss of vitality in the vessel greatly ac- 
celerated the process of coagulation. Dr. Richardson alludes to these experiments, but says they have 
been invalidated by subsequent investigations by Scudamore. I have not as yet seen Sir Astley’s own 
account of his researches on the subject, but, from a notice of them by Palmer, in his edition of Hunter’s 
works, I suspect that they do not deserve to be set aside so lightly. 


78 ON SPONTANEOUS GANGRENE FROM ARTERITIS AND 


the same chemical tendencies as we have seen it to possess when removed from 
the body; and those parts of the fluid which remained at rest under these 
conditions, namely, the motionless layer of liquor sanguinis next to the lining 
membrane, and the portions of blood in the sinuses of the valve, underwent 
coagulation, yielding up their ammonia through the permeable coats of the vein. 
And I think we need not hesitate to admit that similar occurrences take place 
in the early stages of arteritis and phlebitis, the coats of the vessels being in 
those cases not dead, but impaired in vital energy by inflammation. 

A similar explanation appears to account for the early formation of coagula 
in the vicinity of a ligature placed upon an artery. It has been seen how utterly 
the usual explanation, that of the quiescence of the blood, fails to account for 
the phenomenon; but the fact that lymph is afterwards exuded from this 
part of the vessel shows that the case is really one of limited traumatic arteritis. 

But if the coagulation within inflamed vessels thus receives a solution 
from the results of the last-mentioned experiment, still more unequivocally, 
at least to most of my hearers, is the coagulation in gangrene explained, such 
as occurred, for instance, in the case which has been described. 

Again, it is well known that contused wounds bleed very little, the ends of 
the divided arteries becoming speedily plugged with a long coagulum. The 
only explanation which Sir Charles Bell could offer of this remarkable provision 
of nature was, that the living vessels had a special faculty of preventing the 
blood from exercising friction upon their lining membrane, but that the con- 
tused artery, having lost its vitality, the blood became arrested by friction 
and coagulated. We now see that there was much more truth in this theory than 
has been generally supposed, though the loss of vitality in the vessel does not 
operate in the manner which Sir Charles imagined. 

It has been found difficult to understand why the fact of the arteries being 
converted into calcareous tubes should impress upon the blood within them 
a tendency to coagulate in atheromatous degeneration of the vessels. The 
impairment, or entire loss of vitality connected with such a condition, will now 
be found a sufficient explanation. 

The coagulation in aneurysm is now equally comprehensible, the walls of 
the sac consisting either of degenerated or torn coats of the vessel, of inflamed 
surrounding tissues, or of layers of fibrine, each of these constituents being in 
a state of very low vitality. 

The rapid coagulation of lymph, which appears to be neither more nor less 


* I find I have not done justice to Sir C. Bell’s views upon this subject. In his later works he ex- 
presses the opinion that the lining membrane of the living vessels possesses the power of ‘ preserving 
the blood fluid ’, and that the cause of coagulation in a contused artery is the loss of this power in con- 
sequence of the injury.—Vide Sir C. Bell’s Institutes of Surgery, vol. i, p. 52, and vol. il, p. 277. 


THE CAUSES OF COAGULATION OF-THE BLOOD 79 


than the fibrine of effused liquor sanguinis, contrasts, in a very striking manner, 
with the lengthened period during which blood extravasated into the cellular 
tissue may retain its fluidity. But the fact that the liquor sanguinis is exuded 
among tissues that are in a state of inflammation, and so impaired in their 
vital energies, renders the circumstance in question easily intelligible. 

With regard to the nature of the influence exercised by the living vessels 
upon the blood within them, it might be conceived to be either of a positive 
or negative character. It might be imagined, either that the blood has a natural 
tendency within the vessels to comport itself as it does when outside the body, 
and that this tendency is counteracted by an active operation of the living 
tissues, or, that the vital fluid tends to no such change except when prejudicially 
acted on by surrounding objects, which in that case might be supposed to 
exert upon it attractive forces such as tend to group the molecules of dead 
matter together in aggregation, while the living tissues were destitute of such 
action, and simply neutral in their conduct towards the blood. Of these, the 
former has always appeared to me the more likely, a prior, but I had not 
expected to have met with any facts to give distinct evidence either in one 
direction or the other upon a subject so recondite. A simple observation, how- 
ever, made on the sheep’s foot, appears to throw clear light on the matter. 
I have frequently observed that when a vein has been opened and has remained 
patent, the blood has continued fluid in the aperture for a very much longer 
time than is necessary to produce coagulation of a portion of that blood placed 
in a saucer. When the wound in the vein has been a narrow one, I have seen 
the blood remain fluid between its lips for three hours together, though perfectly 
at rest. I have even observed where a portion of fluid blood has been pressed 
from a vein into a groove in the tissues, formed by muscle below, periosteum 
on one side and tendon on the other, this portion of blood has remained fluid 
for an hour, while another drop removed into a saucer at the same time from 
the same vein, has coagulated in a quarter of an hour. Now, in all these cases 
the blood was fully exposed to the influence of the atmosphere ; and if the air 
had been an active agent, promoting the tendency to coagulate, and the tissues 
merely neutral in their operation, coagulation must have occurred rapidly. 
On the other hand, if we admit that the tissues exert an active influence on the 
blood, and that air, oil, and other inorganic matter is inert with regard to it, 
the retarded coagulation follows naturally... Here, then, it appears to me, we 

* Since this paper was read, I have obtained further evidence which will, I trust, appear quite 
conclusive regarding the entirely negative influence of the atmosphere upon the blood, with respect 
to promoting the tendency to coagulation. Just forty-eight hours after the death of the sheep which 


furnished preparations exhibited to the Society, I exposed a vein of one of the feet and injected air 
forcibly into it, by means of a condensing syringe with a fine injection pipe adapted to it. Seven hours 


80 ON SPONTANEOUS GANGRENE FROM ARTERITIS AND 


have a sure, though imperfect glimpse, of the operation of mysterious but 
potent forces, peculiar to the tissues of living beings, and capable of reversing 
the natural order of chemical affinities ; forces which I suspect will never be 
fully comprehended by man in the present state of his existence, and the study 
of which should always be approached with humility and reverence. 

Having thus obtained evidence of the active operation of the living tissues 
upon the blood, it occurred to me that the walls of the vessels might probably 
act to greater advantage upon their contents when of small than of large calibre, 
and that, in that case, the blood might be found fluid in the small vessels of 
the human body after death, although coagulated in the heart and large vessels. 
Accordingly, I have examined three human bodies with regard to this point, 
and in every case have found my idea confirmed. One of these was a woman, 
aged seventy, who had been a patient under Dr. Gillespie’s care at the Infirmary, 
with senile gangrene. The right cavities of the heart were full of blood, and 
contained large clots buffed on their upper surface, and the large vessels also 
contained abundant soft coagula, but a small vein from one of the thighs yielded 
fluid blood, which coagulated slowly in a saucer. The body was examined 
about thirty-six hours after death. The other two had been patients under 
Dr. Gairdner’s care, also in the Royal Infirmary. One of these was a man 
about thirty, who had died of meningitis. The heart had been removed before 
I saw the body, but the large vessels, such as the external iliac vein, contained 
coagula, whereas all the small veins which I observed contained perfectly fluid 
blood, which, however, had lost the power of coagulation. The third case 
was that of a young man, aged twenty-one, who died of a complication of medical 
and surgical complaints, nearly forty-eight hours before the body was examined. 
The corneae were perfectly clear, and there was no appearance of any incipient 
decomposition. This case was investigated very carefully ; and as the subject 
is novel, it may be well to give the results in detail:—I was not present 
later I again examined the foot, and on reflecting the skin from the opposite aspect of the limb, found 
there a large subcutaneous vein distended with a mixture of blood and air; the latter, which had 
evidently passed through an anastomosing channel, being present in the form of very numerous large 
and small bubbles. Having secured the ends of a long piece of this vein, I dissected it out and shed 
its blood into a saucer. Not a particle of clot existed in the vein, and complete coagulation took place 
within a quarter of an hour. The vein which had been exposed, in order to inject the air, contained 
here and there portions of clot in the exposed part, the vitality of the vessel having doubtless been 


mpaired by the mechanical violence to which it was subjected in the dissection, or by the drying 
nfluence of the atmosphere. 

In order to illustrate the effect of mechanical violence applied to a vessel in promoting the coagula- 
tion of the blood within it, I pinched a vein of the same foot severely with dissecting forceps in about 
an inch of its length, at the same time that I injected the air into the other vein. On examining the 
foot, seven hours later, the vein which had been pinched contained coagulum in the part which had 
been so treated, but fluid blood in the rest of its extent, both above and below the injured portion.—J. L., 
March 19, 1858. 


THE ;CAUSES OF COAGULATION OF THE BLOOD 81 


when the heart was removed, but Dr. De Fabeck (resident physician under 
Dr. Gairdner) informs me that the cavities contained coagula buffed on their 
upper surface. The vena cava, the right iliac veins (common, internal, and 
external), and the femoral vein for about four inches down the thigh, contained 
soft coagula, mixed with thick dark fluid blood. The upper part of the axillary 
vein and the internal jugular of the same side, also contained some soft dark 
coagula, but the deep epigastric, the femoral vein below the part before men- 
tioned, the internal saphena, and a smaller venous branch in the thigh, the 
axillary, except at the upper part, the cephalic, and a subcutaneous vein of the 
throat, all contained fluid blood, which coagulated in about half an hour after 
being shed; and I noticed in the thigh that the blood from a small venous 
branch coagulated more quickly than that from the saphena. In the veins 
of the lower limb, both large and small, there were curious strings of highly 
elastic tawny fibrine, but these had evidently been deposited long before death. 
Similar threads were also present in the veins of the neck and in the aorta, 
external iliac, and femoral arteries, which, however, contained but little blood, 
and no post mortem coagula. I did not test the coagulability of the blood in 
the arteries, nor in a branch of the internal iliac vein, which also contained 
fluid blood. 

I am aware of one source of fallacy in these experiments, namely, that the 
abdominal viscera are subject to decomposition before the limbs ; and as soon 
as decomposition does set in, the blood coagulates in the parts which are the 
seat of it; as, for example, in small veins of the intestines. This cause of error 
was, however, I think, guarded against in the last case ;1 and considering the 


’ Through the kindness of my friend Mr. John Gamgee, of the New Veterinary College, I have had 
the opportunity of making further observations regarding this point, upon an animal with very large 
blood-vessels, so soon after death as to avoid the risk of incipient decomposition. A healthy horse 
having been killed by pithing, at 11.30 p.m. on the 22nd inst. (March 1858), I examined the body just 
twelve hours later, while it was still warm. The cavity of the thorax, when opened, smelt perfectly 
fresh. Both auricles contained large masses of coagulum, buffed on their upper surface. There were 
also soft dark clots in both ventricles, together with a good deal of fluid blood, which, however, scarcely 
coagulated at all, a considerable portion from the right ventricle yielding, after many minutes, only 
a minute thread of fibrine. I suspect this was chiefly serum and corpuscles, which had passed in from 
the auricles on relaxation of the ventricles. There was a considerable amount of firm coagulum in 
the aorta, and the large veins at the anterior part of the chest were loaded with firm buffed clot. 
A small branch beneath the pleura, where it is reflected over the pericardium, contained perfectly fluid 
blood, as also did a coronary vein of the heart, about as large as the saphena of the human thigh ; 
whereas the concomitant artery, which was very large (bigger than the human femoral), had the blood 
a good deal coagulated. That from the coronary vein, having been shed into a saucer, yielded, after 
some time, threads and lumps of fibrine. An intercostal vein, from beneath the pleura, as big as a crow- 
quill, furnished fluid blood, which coagulated. The superficial veins of both fore-legs yielded perfectly 
liquid blood, which began to coagulate in about four minutes, and set into a solid mass. But, just 
below the axillary, small portions of coagulum made their appearance in the vessels, which here attained 
a size about equal to the femoral in man; and both the axillary trunks were plugged with firm clot. 


LISTER 1 G 


82 ON SPONTANEOUS GANGRENE FROM ARTERITIS AND 


almost universal occurrence of coagulum in the heart of the human subject 
twenty-four hours after death, compared with the universal absence of it in 
the small veins of healthy parts, so far as I have yet examined them, both 
in man and the lower animals, I think the fact must be admitted, that where 
a large mass of blood exists within a cavity of the heart or a blood-vessel, it 
experiences coagulation sooner than if in a small vessel of the same body. If 
this be admitted, it becomes a strong argument in favour of the active operation 
of the tissues, for the blood is more exposed to the influence of the air in a sub- 
cutaneous vein than in the heart, and the only conceivable reason for the 
greater persistence of fluidity in the latter than in the former is that the 
influence of the tissues operates to greater advantage upon the smaller mass 
of blood. 

Again, supposing it to be admitted that free ammonia exists within the 
blood-vessels, maintaining the fibrine in solution, a hypothesis which, I confess, 
appears to me very probable,—granting the ammonia theory, I say, as far as 
it can possibly be granted, it is clear that no merely neutral action of the tissues 
could check the evolution of the alkali in the manner above described ; and 
nothing can tend to convince us more of the potency of the vital forces than 
to consider what new powers must be impressed upon the chemically inert 
constituents of the tissues, in order to enable them securely to chain down 
the alkaline gas, in spite of its excessive volatility. 

There is one other experiment upon the sheep’s foot which I do not like 
to omit mentioning. Having exposed a subcutaneous vein, six hours after the 
death of the animal, I pressed out the blood from an inch of it, and treated 
the empty part with caustic ammonia, the adjacent parts being protected by 
olive oil. When the smell of ammonia had passed off, I let the blood return, 
and, two or three hours after, found that the portion which had had its vitality 
destroyed by the ammonia, was full of clot, while the blood in the adjacent 
parts of the vein was fluid, and coagulated on exposure.! 

This, however, was not the only result of the application of the ammonia. 
The surrounding tissues had not been thoroughly protected from its action 
by the oil, and next morning all the parts on which it had acted were the seat 
of the most intense congestion, accompanied with exudation of glairy matter into 
the cellular tissue ; in fact, there were all the appearances of the most severe 


* Two feet of a sheep, killed six hours before the Society met, were exhibited in illustration. One 
of these was prepared in the manner described in the text. The portion of vein which had been treated 
with ammonia contained a cylindrical coagulum, while the blood in the adjacent parts of the same 
vessel was fluid. The other foot was for the purpose of showing the fluidity of the blood so many hours 
after death. A considerable amount having been shed into a saucer in the liquid state, soon assumed 
the solid form. 


ter 


THE CAUSES OF COAGULATION OF THE BLOOD 83 


inflammation. Some of the exuded matter had trickled down on a board 
beneath, and had there coagulated, showing that genuine exudation of lymph 
had been the result of this post mortem inflammation, then, I believe, for the 
first time observed in one of the mammalia.’ I cannot avoid expressing the 
satisfaction that it has given me to find what I had inferred from other cir- 
cumstances, in my investigations on inflammation, now established as a matter 
of observation. I had found that the blood-corpuscles, both red and white, 
were perfectly free from adhesiveness within the vessels of a healthy part, but 
that in an inflamed region they stuck together just as they are seen to do between 
two plates of glass. Having thus observed that the corpuscles of the blood 
comport themselves in an inflamed part in the same manner as in blood drawn 
from the body, I inferred that the liquor sanguinis was, in all probability, 
similarly affected, although coagulation is not observed in the capillaries, in 
consequence of the movement of the blood; and I gave the same explanation 
of the speedy coagulation of lymph, and of the formation of clots in inflamed 
vessels, as has been substantiated by independent facts this evening. In the 
paper before alluded to, the following passage occurs :—‘ The non-adhesiveness 
of the red and white corpuscles, and the fluidity of the blood, seem to be due 
to one and the same mysterious and wonderful agency—the tissues of a healthy 
body appearing to extend over the blood near them, a part of the same influence 
by which they are themselves protected from the action of chemical affinities 
tending to their decomposition.” We now see that when an agent capable of 
producing inflammation acts upon a part in which the blood is at rest, 
coagulation of the blood does really occur in the vessels. 

There is an error of observation into which Dr. Richardson has un- 
accountably fallen, which it appears important to correct. In speaking of the 
coagulation of a portion of blood enclosed between two ligatures in the jugular 
vein of a dog or cat, he mentions the formation of a large bubble of air within 
the vessel, a little prior to the occurrence of coagulation. I have frequently 
seen the pellucid appearance he describes, but find that it is in no way con- 
nected with coagulation, but is due to the subsidence of the red corpuscles, 
leaving a layer of clear liquor sanguinis at the top. If two ligatures be applied, 
about an inch apart, upon a subcutaneous vein of one of the legs of a cat, care 
having been taken not to disturb the connexions of the vessel, or inflict injury 
upon it, and the leg be suspended by the paw in the vertical position, the clear 
appearance will begin to show itself below the upper ligature within five minutes. 


1 Tension upon the blood in the vessels, resulting from the bandage, supplied, I imagine, the place 
of the force of the heart in squeezing out the liquor sanguinis through the walls of the capillaries, de- 
prived of their usual power of retaining it. 

G2 


84 ON SPONTANEOUS GANGRENE FROM ARTERITIS, ETC. 


If now the limb be left for several hours, the skin having been carefully replaced 
so as to prevent evaporation, the clear colourless upper layer will be found 
to occupy nearly two-thirds of the length of the portion of vein, and to be sharply 
defined from the black lower layer which contains all the red corpuscles. If 
now the upper part be punctured, the clear liquor sanguinis will flow out, and 
coagulate upon any object held to receive it.’ 

Some of the observations above described will have a bearing upon medico- 
legal inquiries, showing, as they do, that not only ecchymosis, which some have 
denied, but even inflammation may be developed post mortem, provided that 
the return of blood by the veins is in some way prevented. 

There are other bearings, both upon pathology and practice, to which 
I cannot even allude on the present occasion; but I thought it best to place 
the facts at once before my professional brethren, confident that they will 
receive from them all the attention that they may deserve. 

In conclusion, I have to express my thanks to my friend, Mr. Craig, for 
the kind and able assistance which he has afforded me throughout this investiga- 
tion, and also to my friends, Drs. Gourlay and Hill, who have on several occasions 
lent me most valuable aid. 


* Post mortem congestions simulating inflammation are, I suspect, due to this gravitation of the 
red corpuscles of the still fluid blood into the vessels of dependent parts. 


AY OGASEFOP ILIGATURE OF THE BRACHTAL ARTERY, 
ILLUSTRATING THE PERSISTENT VITALITY OF 
THE TISSUES 


[Edinburgh Medical Journal, vol. iv, p. 119, August 1858.] 


ON the 28th of May last I was requested to see a case at Balfron, in Stirling- 
shire, under the care of Mr. Burgess, who stated that on the roth of April the 
patient, a man about fifty years of age, inflicted a suicidal wound with a razor 
on the front of the left arm about three inches above the elbow, severing the 
biceps completely and dividing both the main superficial veins of the limb. 
The bleeding was very profuse but chiefly venous, and was readily controlled 
by pressure, and the wound was afterwards lightly dressed without anything 
unusual occurring for several days, when haemorrhage again took place to 
a very alarming extent. It was treated as before by compression, but recurred 
twice at intervals of a few days, after which for a period of more than three 
weeks the healing process appeared advancing favourably. On the 24th of May, 
however, there was another discharge of blood from the wound, and this was 
repeated at frequent intervals and with increasing violence in spite of com- 
pression, until the 27th, when it became imperative to have recourse to other 
measures. Inconvenience in the arrangements of the railway delayed my 
arrival nearly a day, and in the meantime it had been found necessary to apply 
bandages at the seat of wound with all possible force, so as completely to arrest 
the flow of blood through the vessels of the limb, which had thus been entirely 
devoid of circulation for about thirty hours before the time at which I first 
saw the patient, viz. 2 p.m. on the 29th. At this time he was lying in bed pale 
and weak from loss of blood with the left arm somewhat swelled below the 
bandages, livid in tint and quite cold. Chloroform having been administered 
I removed the bandages, after which arterial blood gushed from the wound as soon 
as ethe pressure of the fingers over the brachial artery was relaxed. With the 
assistance of Mr. Burgess I proceeded to expose the bleeding-point, and after 
a somewhat troublesome dissection among the tissues, densely matted together 
with inflammatory deposit, discovered a small wound in the brachial artery, 
and having cleared the vessel sufficiently to avoid the risk of including either 
of the adjacent nerves, passed ligatures around it above and below the aperture, 
with the effect of removing all tendency to haemorrhage. Before I left in the 


86 A CASE OF LIGATURE OF THE BRACHIAL ARTERY 


afternoon the limb had already recovered its warmth and Mr. Burgess has since 
informed me that feeble pulsation was soon after perceptible at the wrist. In 
his last letter, written on the 21st of June, he stated that the ligatures had 
come away several days previously, the wound was healing kindly, and there 
was good sensation in the limb, though not quite so acute as in the other arm, 
while the patient was regaining health and strength. 

This case is an example of the practical application of the principles sought 
to be established in a paper lately published. in this journal,’ in which it 
was shown that tissues previously healthy retain their vitality for a much longer 
period than had been before supposed after complete withdrawal from the 
influence of the centres of circulation and innervation; and that by virtue 
of this persistent vitality the blood continues fluid for several days within the 
vessels of an amputated limb. In the present case the appearances of the arm 
and the previous history were such as would, I believe, have induced most 
surgeons not conversant with these principles to have resorted at once to 
amputation. 

* Vide a paper by the author ‘On Spontaneous Gangrene from Arteritis and the Causes of Coagula- 


tion of the Blood in Diseases of the Blood-vessels’. Edinburgh Medical Journal, April 1858 (p. 69 of 
this volume). 


PRELIMINARY ACCOUNT OF AN INQUIRY INTO 
THE FUNCTIONS OF THE VISCERAL NERVES, 
WITH SPECIAL REFERENCE TO THE SO-CALLED 
TENEIIBIEORY SYslEM ”’ 


In A LETTER TO DR. SHARPEY, SEC. R.S. 
[Proceedings of the Royal Society of London, vol. ix, No. 32 (1858).] 
Received August 13, 1858. 


My DEAR SiR.—The fact that the irritation of visceral nerves sometimes 
causes arrest of the movements of organs supplied by them, as shown by 
Edward Weber’s experiment of stopping the action of the heart by stimulating 
the vagus, and by Pfltiger’s more recent observation that the application of 
galvanism to the splanchnic nerves produces quiescence of the small intestines, 
appears to me to have an intimate bearing upon the question how inflammation 
is developed through the medium of the nervous system at a distance from 
an irritated part; and as the nature of the inflammatory process has lately 
engaged my special attention, I have been led to make an experimental inquiry 
into this ‘inhibiting’ agency, the true interpretation of which is, as you are 
aware, still swb judice. I now propose to state the principal results at which 
I have arrived, reserving further details for a more extended communication 
which I hope soon to offer the Royal Society. 

The view which has been advocated by Pfltiger,, and I believe very 
generally accepted, viz. that there is a certain set of nerve-fibres, the so-called 
‘inhibitory system of nerves’ (Hemmungs-Nervensystem), whose sole function 
is to arrest or diminish action, seemed to me from the first a very startling 
innovation in physiology ; and you may possibly recollect my mentioning to 
you in conversation, when in London last Christmas, my suspicion that the 
phenomena in question were merely the effect of excessive action in nerves 
possessed of the functions usually attributed to them. On further reflection 
upon the subject, the consideration of the contraction produced in the arteries 
of the frog’s foot by a very mild stimulus, as compared with the relaxation of 
the vessels caused by stronger irritants acting through the same nerves, con- 
firmed my previous notions. For I could hardly doubt that the cause of the 


1 Eduard Pfliger, Ueber das Hemmungs-Nervensystem, 1857. 


88 PRELIMINARY ACCOUNT OF AN INQUIRY INTO 


quiescence of the heart or intestines on irritation of the vagus or splanchnic nerves 
was analogous to that of arterial dilatation in the web, and that, provided a suf- 
ficiently mild stimulus were applied to the so-called ‘inhibitory nerves’, increased 
action of the viscera would occur, corresponding to the vascular constriction. 

To test the truth of this hypothesis, I made several experiments between 
the 17th of June and the 14th of July of this year, with regard to the movements 
of the heart and intestines. The means used for stimulating the nerves and 
spinal cord were sometimes mechanical irritation, but more commonly galvanism, 
applied with a magnetic coil battery of a single pair of plates, the strength of 
which could be regulated in a rough way, with great facility, by the height 
at which the acid solution stood in the jar and the extent to which the rods 
of soft iron were inserted in the helix. The mildest action employed was such 
as was but just perceptible to the tip of the tongue, placed between the fine 
silver-wire extremities of the poles, when the rods were fully in the helix, but 
inappreciable after their complete withdrawal; the spring carrying the 
magnetic bar being made to vibrate by a touch with the finger: the greatest 
action of the battery, on the other hand, was so powerful as to elicit sparks 
when the poles were applied to the tissues. 

My attention was first directed to the intestines, and it may be well to 
mention first all the results obtained with reference to them. The animals 
operated on were generally rabbits, they being very easily managed, and also 
favourable for the purpose on account of the large amount of movement which 
occurs in their intestines. Chloroform was generally not administered, on 
account of its depressing effect upon the action of the nervous centres. 

In the first experiment, the ends of the poles having been fixed to the 
spinous processes of the ninth and twelfth dorsal vertebrae, according to Pfliiger’s 
original method, and the intestines allowed to protrude through a wound in 
the abdominal parietes, a series of interrupted currents were transmitted, a very 
small amount of acid being in the jar, and the rods fully in the helix. The 
effect was complete relaxation and quiescence of the small intestines, which 
had been previously in considerable movement, while the muscles of the limbs 
were thrown into spasmodic action ; but on the discontinuance of the galvanism 
the previous intestinal motion returned. The rods were then removed from the 
helix, and the battery, thus diminished, was applied on several occasions, with 
markedly increased action of the intestines in every instance during the first 
twenty-five minutes. In the next half-hour the increase of action from the 
galvanism, though still distinct, was less strongly marked; and at the end 
of that period, the rods having been reintroduced, the inhibiting influence 
was also found to be much less complete than before, indicating that the parts 


THE BUNCHIONS OF THE VISCERAL NERVES 89 


of the nervous apparatus concerned were in a less active condition, no doubt 
in consequence of exhaustion. The arches of the tenth and eleventh dorsal 
vertebrae having been removed before the experiments with galvanism, I sub- 
sequently introduced a fine needle into the exposed part of the cord, with the 
effect of causing in repeated instances increased movements of the intestines, 
which were especially striking on account of the occurrence of peculiar local 
contractions not seen at other times. Further observations upon this animal 
tended to confirm those which have been mentioned, as did an experiment 
of the same kind performed the next day upon another rabbit. 

I afterwards found that the best mode of proceeding was to remove the skin 
and one or two layers of muscles from a portion of the abdomen till the parietes 
were sufficiently thinned to permit the intestines to be distinctly seen through 
them ; by this means the complication produced by exposure of the intestines 
to the atmosphere was avoided, and the most satisfactory results were obtained ; 
the increase of the peristaltic movements during the transmission of extremely 
feeble shocks being strikingly apparent and constant on every occasion. During 
the experiment performed in this way I noticed several times that a violent 
struggle on the part of the rabbit, when the intestines were in pretty free move- 
ment, was followed by absolute and universal quiescence of those organs for 
several seconds; this appeared to me of great interest, as proving that the 
inhibitory influence is certainly sometimes exerted in the natural actions of 
the animal, and is.not merely the result of artificial stimulation. 

In the course of the above experiments several other observations were 
made. In the first place I verified the statement of Pfliiger, that if, when the 
intestine is lying relaxed under the inhibiting influence of galvanism applied 
to the spine, a particular part be irritated, local contraction occurs, but is not 
propagated to neighbouring parts. This fact is of fundamental importance, 
since it proves that the inhibitory influence does not operate directly upon 
the muscular tissue, but upon the nervous apparatus by which its contractions 
are, under ordinary circumstances, elicited. 

Another point which seemed to require investigation was the well-known 
increase of peristaltic action which takes place after death, and which continues 
in spite of cutting off the mesentery close to the gut. Those who believe in 
a constantly restraining function of certain nerves during life might argue that 
the intestine has always a tendency to such active movements, but is kept 
in check by the ‘inhibitory nerves’, and released from their control when 
they have lost their power after death. A different explanation, first suggested, 
I believe, by Bernard, is that the increased action of the intestines is the result 
of failure of the circulation in the part ; and to this view I felt disposed to agree, 


go PRELIMINARY ACCOUNT OF AN INQUIRY INTO 


in consequence of having noticed curious irregular contractions in the arteries 
of the frog’s foot from a similar cause. In order to decide the question, I tied 
three adjoining arterial branches in the mesentery of a rabbit, thus depriving 
about three inches of the intestine of its circulation, the parts so affected 
being accurately defined by the extent of absence of pulsation in the minute 
vessels close to the gut. In about a minute and a half, vermicular movements 
commenced in this part, the rest of the intestines being at the time very quiet. 
Powerful interrupted galvanic currents were then transmitted through the 
posterior dorsal region of the spine, with the effect of causing perfect quiescence 
of the whole of the intestine, including the part whose arteries had been tied. 
After cessation of the galvanism the movements recurred in the portion devoid 
of circulation, while elsewhere they were almost entirely absent. This experi- 
ment was repeated on another occasion with similar results. In one of the 
cases I divided the mesentery close to the gut, after ligature of the vessels, 
but no change took place in the character of the movements which had been 
previously induced, indicating that the increased action in these cases had been 
of the same nature as that which results from death. The arrest of the move- 
ment on the application of galvanism proved that the delicate operation of 
ligature of the mesenteric vessels had been performed without injury to the 
adjacent nervous branches; and it therefore followed that the movement 
in the parts supplied by those vessels was not due to any injury of the nerves, 
but simply to the arrest of circulation. It further appears from these experi- 
ments, that, in whatever way the cessation of the flow of blood through the 
vessels operates in increasing the peristaltic action, it does so through the medium 
of the nervous apparatus, and not by directly influencing the muscular tissue. 
For, in the latter case, the movement would have continued in spite of the in- 
hibiting influence, which, as we have seen, has no effect upon muscular irritability. 

The fact that the movements continue in a portion of gut deprived of its 
mesentery, proves that the nervous apparatus by which the muscular contrac- 
tions are induced and co-ordinated in post mortem peristaltic action, is con- 
tained within the intestine. 

The distinction between the co-ordinating power and muscular contractility 
was very strikingly shown in the further progress of one of these experiments. 
The peristaltic movements of the portion of gut supplied by the ligatured 
arteries ceased entirely about twenty minutes after the vessels were tied, and 
the surface of the gut became there perfectly smooth and relaxed, contrasting 
strongly with the wrinkled aspect of other parts. But muscular irritability 
had outlived the co-ordinating power, as was shown by energetic, purely local 
contraction taking place in a part pinched. Similar observations confirmatory 


He BiINGiIONS OF THE VISCERAL NERVES Ope 


of this point were afterwards made upon a rabbit which had died of haemorrhage 


C 


an hour before. 

The mechanism by which the muscular contractions are regulated is, 
doubtless, the rich ganglionic structure lately demonstrated in the submucous 
tissue by Dr. Meissner of Bale.t Professor Goodsir gave me the first information 
of the anatomical fact on my mentioning to him the foregoing physiological 
proofs of the existence within the intestines of a co-ordinating apparatus distinct 
from the muscular tissue. I have since verified Meissner’s observations, and 
found abundant well-marked nerve-cells in the submucous tissue of the ox, 
exactly corresponding with his descriptions. 

But while muscular irritability outlives the co-ordinating power in the 
intestines, the latter lasts much longer than the inhibiting property in the 
spinal system, for I find that Pfliiger’s experiment does not succeed in a dead 
animal, unless performed soon after death, although the intestines may continue 
to move for a long time. 

In another experiment I divided with fine scissors, at a little distance 
from the intestine, all the visible branches of nerves in a portion of mesentery 
corresponding to an inch and three-quarters of the gut, leaving the vessels 
uninjured. No effect was produced on the peristaltic movements, which hap- 
pened to be pretty active at the time, and continued the same at the seat of 
the operation as elsewhere. To ascertain whether the division of the nerves 
had been thoroughly effected, I now transmitted powerful galvanic currents 
through the spine, as in former experiments, when all movements ceased in 
the intestine, except in the small piece whose nerves had been cut, which 
continued in vigorous action as before. The persistence of the vermicular 
motion after complete division of the mesenteric nerves shows that the move- 
ment which occurs during life, ike that which takes place post mortem, 1s effected 
by a mechanism within the intestine; and its continuance in the portion of 
gut so treated, while other parts were relaxed, on the application of galvanism 
to the spine, proves that the inhibiting influence acts through the mesenteric 
nerves, whose integrity is necessary to the effect. 

This being established, it follows that if a quiet state of the intestine, 
such as very frequently occurs in its natural condition, were due to a con- 
trolling agency on the part of the so-called ‘ inhibitory system’, the complete 
division of the mesenteric nerves supplying a portion of gut which is at rest, 
would liberate it from this restraint, and movement would be the result. I per- 
formed the operation in one case under such circumstances, but the portion ot 
intestine concerned remained as tranquil as the rest. 


1 Henle and Pfeufer’s Zeztschrift, 2nd series, vol. vill. 


g2 PRELIMINARY ACCOUNT OF AN INQUIRY INTO 


To sum up the above, it appears that the intestines possess an intrinsic 
ganglionic apparatus which is in all cases essential to the peristaltic movements, 
and, while capable of independent action, is hable to be stimulated or checked 
by other parts of the nervous system ; the inhibiting influence being apparently 
due to the energetic operation of the same nerve-fibres which, when working 
more mildly, produce increase of function. 

After the above conclusions had been arrived at, my attention was directed 
by Professor Goodsir to a paper by Dr. O. Spiegelberg, published last year, 
in which he shows that the movement of the intestines is increased by 
mechanical irritation of the cord. His results are particularly satisfactory, as 
having been obtained incidentally during an inquiry into the movements of 
the uterus, and so without any preconceived theory. Spiegelberg also attri- 
butes the increased peristaltic action after death to arrest of the circulation, 
having found that the same thing occurs during life when the aorta or vena cava 
is compressed above the origin of the mesenteric vessels. 

To proceed to the experiments upon the cardiac movements : some of these 
consisted in irritation of the vagus in rabbits, and this was followed by different 
results in different instances: thus, on one occasion the pinching of the cardiac 
end of the left nerve, divided in the neck, was followed by considerable increase 
in the number of beats as felt through the walls of the chest, but similar treat- 
ment of the right nerve afterwards caused great depression of the heart’s action. 
Again, in one animal the evidence obtained from mechanical irritation of the 
vagus was almost entirely negative. In another case, the left vagus having been 
exposed, feeble galvanic currents transmitted through the nerve, isolated by 
a plate of glass placed beneath it, were succeeded by slight increase in the 
number of contractions. The strength of the battery having been then in- 
creased by introducing the rods into the helix, it produced first irregularity, 
and then complete arrest of the action of the heart, which had been previously 
exposed. No sign of recurrence of contraction appearing, I filled the jar to the 
top with acid solution, and sent powerful currents through the vagus, with the 
instantaneous effect of reviving the action of the heart, which, on their immediate 
discontinuance, continued to beat, though feebly, for several minutes. During 
this time I again applied the galvanism very mildly, and the result was great 
increase in the number of beats on several successive trials. The apparent 
discordance of these facts is, I believe, partly owing to differences in the state 
of the nerves in different cases as respects irritability and exhaustion, as will be 
better understood from the sequel ; and, on the whole, the experiments appear 
to show that, in a healthy state of the nervous system, very gentle irritation of 


‘ Henle and Pfeufer’s Zezischrift, 3rd series, vol. il, part 


THE EUNCEIONS OF THE VISCERAL NERVES 93 


J 


the vagus increases the heart’s action, while a slightly stronger application 
diminishes the frequency and force of its contractions. This conclusion is in 
harmony with an observation which I made incidentally upwards of a year 
ago, that irritation of the posterior part of the brain of a frog with a fine needle 
was repeatedly followed by improvement in the circulation, whereas it was 
by the application of a stronger stimulus, that of galvanism, to the same 
part of the cerebro-spinal axis that Weber first induced an inhibitory action 
on the heart. 

It is said, on apparently good authority,’ that division of the vagus in 
mammialia is invariably followed by increase of the action of the heart ; this, 
if true, would be a strong ground for believing in an inhibiting influence con- 
stantly operating upon it through this nerve. But it is also stated that the 
same thing does not occur in frogs ; and this circumstance appeared to me to 
throw much doubt upon the evidence regarding mammalia. I therefore made 
careful experiments on the effects of cutting both vagi, once upon a calf and 
four times upon rabbits, taking the number of the heart’s beats immediately 
before and immediately after section of each nerve by the momentary stroke 
of a sharp pair of scissors. In no case was the rate increased at all by the 
operation, and the very gradual diminution in frequency that commonly took 
place appeared to depend on general exhaustion from other circumstances 
attending the experiment. In one rabbit, in which I had removed the skin 
and pectoralis major from the praecordial region, so as to see the movements 
of the heart distinctly through the transparent pericardium and _ intercostal 
muscles, I noticed particularly that the strength of the contractions, as well as 
their frequency, remained quite unaffected by the division of the vagi. From 
these facts I feel warranted in concluding that, whatever may occur under 
exceptional circumstances, there is certainly no constant control exercised 
over the heart’s action through those nerves. 

The influence of the spinal system upon the heart is, however, very apparent 
after a struggle, which almost invariably increases the frequency and force of 
the beats; and I found that this continued to be the case after division of both 
vagi, implying that those nerves are not the only channels through which this 
influence is transmitted. A new field of investigation was thus opened. For, 
supposing the inhibitory agency to be simply the greater action of an ordinary 
nerve, it would probably not be exercised exclusively by the vagus, but also 
by the other nerves connecting the cerebro-spinal axis with the cardiac ganglia, 
viz. the sympathetic branches in the neck ; in which case the action of the heart 
should be increased or diminished, according to the strength of the stimulus, 


= Pileer,-op. cit. 


94 PRELIMINARY ACCOUNT OF AN INQUIRY INTO 


by the application of galvanism to the cervical region of the spine after the 
pneumogastric nerves had been cut. 

In an experiment performed with this view, the poles having been fixed 
to about the fourth cervical and fifth dorsal spinous processes, and both vagi 
divided in the neck, galvanic currents only just perceptible to the tip of the 
tongue were first transmitted. This excessively feeble action of the battery, 
though apparently not very favourably situated for influencing the cord, pro- 
duced marked effects upon the heart’s action, increasing the number of beats, 
which were about forty in ten seconds, by from three to ten in that period. 
This effect having been observed for a considerable time, the rods of soft iron, 
which had been till then only inserted half-way in the helix, were pushed fully 
in. The battery, thus strengthened, instead of increasing, as before, the rate 
of the pulsations, diminished it by two in ten seconds on several successive 
trials. On again half withdrawing the rods, the galvanism, when applied, again 
increased the number of beats. A little more of the acid solution was after- 
wards poured into the jar of the battery, when the stronger currents which it 
produced reduced the number by about five in ten seconds. 

Yet distinct as was this inhibiting influence, the shocks were still quite 
tolerable to the tongue even when the rods were fully in the helix. 

These results were of great interest, as proving how slight an increase 
of the feeble stimulus which promoted the action of the heart sufficed to produce 
the opposite (inhibiting) effect. But it was by no means clear that the influence 
had not been exerted through cardiac branches arising from the vagi above 
the parts where they were divided, or even through the trunks of those nerves, 
which might possibly have been affected by the galvanism acting through the 
superjacent spinal column. In order to eliminate the vagi completely, I divided 
in another rabbit all the soft parts in front of the spine, except the trachea 
and oesophagus, at the level of the cricoid cartilage, having previously cut each 
carotid artery between two ligatures. The incisions were carried fairly down 
to the bodies of the vertebrae, and outwards beyond the tips of the transverse 
processes, so as to ensure the section not only of the vagi and their branches, 
but also of the sympathetic cords, with any filaments of those nerves which 
they might contain. Also the poles of the battery were fixed to the spinous 
processes of the seventh dorsal and first lumbar vertebrae, so as to avoid all 
possibility of direct action of the galvanism upon either the vagi or other cardiac 
nerves. Feeble currents being then transmitted, diminution of the number 
of beats to the extent of two to four in ten seconds occurred in several successive 
trials, the results being so constant as to leave no doubt that they were produced 
by the galvanism. 


THE PUNGCTIONS OF THE VISCERAL NERVES 95 


It may appear almost incredible that such extremely mild galvanic currents, 
applied through the spinous processes of the posterior dorsal region, should 
be capable of thus affecting the heart ; but that their effects were really very 
considerable, was clear from the further progress of this experiment, and from 
others somewhat similar, which showed that this apparently trivial stimulation 
eradually exhausted the part of the nervous system through which the heart 
is acted on by the cord. Thus, in one case, currents only just perceptible to the 
tongue, transmitted for about thirty seconds at a time through the lower cervical 
and upper dorsal regions of the spine, at intervals of nine minutes on the average 
during two hours and twenty minutes, produced at first decided increase of the 
heart’s action, but during the last hour failed to affect it at all. The strongest 
possible action of the battery which, as proved by other experiments, would, 
at the outset, have entirely arrested the cardiac movements, was then set on, 
but with no effect whatever on the organ. 

When partial exhaustion has occurred, a much stronger galvanic stimulus 
is required, to produce the same effect upon the heart, than at the commence- 
ment of an experiment; and thus an action of the battery which, when first 
applied, causes marked diminution in the number of beats, may after a while 
come to have the opposite effect, and increase the heart’s action as decidedly 
as it had previously lowered it ; while at an intermediate period it may seem 
to have no influence at all. This principle gives the clue to understanding 
what had before appeared incomprehensible in these experiments, showing that 
facts, which at first seemed utterly inconsistent, were really perfectly harmonious. 
The case before related, in which revival of the heart’s action resulted from 
powerful stimulation of the vagus, which, had the organ been contracting as 
usual, would have arrested its movements and probably finally destroyed them, 
will now be understood. I have seen other analogous cases of revival of action 
by very powerful galvanism, which under ordinary circumstances would have 
arrested it, viz. twice in the heart and twice in the intestines. The observation 
published so long ago as 1839 by Valentin,! that mechanical or chemical irritation 
of the vagus in the neck of an animal recently dead, and with the nerves conse- 
quently enfeebled, causes contraction of the ventricles, admits of a similar 
interpretation, as also does a corresponding fact regarding the splanchnic nerves, 
given without explanation by Kupfer and Ludwig, in a paper just published,” 
viz. that they lose their inhibitory influence a certain time after death, and 
acquire a motor power over the intestines. 

Two more experiments require mention, as they exclude the possibility of 


* Valentin, De Functionibus Nervorum, p. 62. 
* Henle and Pfeufer’s Zeztschrift, 3rd series, vol. ii, part 3. 


96 PRELIMINARY ACCOUNT OF AN INQUIRY INTO 


the agency in them of either the vagi or the part of the brain from which the 
vagi spring, having been performed upon decapitated rabbits. In one of these 
cases, the carotids having been tied near the head, the neck was completely 
severed behind the first vertebra, care being taken to avoid haemorrhage from 
the vertebral arteries, and artificial respiration, for which provision had been 
made, was carried on for an hour and a half after decapitation. The results 
of moderate galvanism, applied to the posterior dorsal region of the spine, to 
which the poles had previously been attached, were at first not distinct, but 
afterwards decided increase of action was produced by it when applied at inter- 
vals during half an hour, the effect being perfectly apparent in the heart which 
lay exposed before me. Exhaustion of the nerves concerned having then taken 
place, the most powerful action of the battery failed to influence the character 
of the contractions. 

In the other case, the poles having been fixed as before, and the head simi- 
larly removed, powerful galvanic currents were immediately transmitted. The 
pulsations of the heart in the opened chest at once fell from thirty-five to sixteen 
in ten seconds, but rose again to twenty on the removal of the stimulus. 

Hence it is clear that the sympathetic branches connecting the cord with 
the cardiac ganglia have equal claims with the vagi to be called ‘ inhibitory 
nerves’. In fact this expression seems to me altogether objectionable, since 
there is good reason to think that the same fibres which check the movements 
much more commonly enhance them. The only evidence afforded by my 
experiments that the inhibiting influence is ever exerted in the natural actions 
of the animal consisted in the quiescence of the intestines sometimes seen after 
a struggle, and two doubtful observations of retardation of the heart’s beats 
from the same cause. Indeed it appears very questionable whether the motions 
of either of these viscera are, under ordinary circumstances, ever checked by 
the spinal system, except for very brief periods ; whereas the increased action 
of both heart and intestines, familiarly known to result from mental emotion, 
may last for a very considerable time. The fact that the nerves of these organs 
are capable of setting them at rest under conditions of extraordinary irritation 
is nevertheless a matter of great importance, especially in a pathological point 
of view, and appears to afford an explanation of facts in medicine hitherto little 
understood—such as failure of the heart’s action from violent emotion or pain, 
and the constipation which attends strangulated omental hernia. 

From the observations of Spiegelberg,’ it would appear that the uterine 
contractions are promoted by mechanical irritation of the cord, and arrested by 
transmitting a powerful stream of galvanism through the spine. Also the forcible 


* Henle and Pfeufer’s Zeitschrift, 3rd series, vol. li, part I. 


THE BUNCTIONS OF THE VISCERAL NERVES 97 


expulsion of urine very frequently seen in the lower animals in consequence 
of fear, and the temporary palsy of the detrusor often witnessed in the human 
subject in surgical practice as the result of severe injury, seem to me to imply 
that the bladder, too, while sometimes stimulated through the cerebro-spinal 
axis, 1s paralysed by its very powerful operation. Hence it seems probable that 
the movements of all the hollow viscera are liable to similar influence from the 
spinal system. At the same time it appears to be a mistake to regard this 
influence in the light of a strict control; for the experiments related in this 
letter show pretty distinctly that the contractions of the heart and the peristaltic 
action of the intestines are regulated, under ordinary circumstances, by the 
independent operation of the intrinsic ganglia. 

Professor Schiff has, I understand, observed increase of the heart’s action 
to result from very gentle stimulation of the vagus,! and has come to the con- 
clusion, as stated by Spiegelberg in his paper before referred to, that the inhibit- 
ing influence depends upon nervous exhaustion. There are some circumstances 
which make me entertain great doubt as to the correctness of this view. In 
the first place, the very rapid recovery of the cardiac or intestinal actions when 
the inhibiting galvanic currents are discontinued, contrasts strongly with the 
length of time that the impairment of function resulting from a protracted 
experiment, and certainly due to exhaustion, lasts both in the intrinsic cardiac 
nerves and in those that connect them with the spinal system. Secondly, 
although very powerful galvanism not only arrests for the time, but permanently 
impairs the action of the heart, no such effect is observed to follow the inhibiting 
influence when it is caused by milder stimulation ; indeed, according to my 
experience, less injurious effects are produced upon the heart by a protracted 
series of experiments of the latter kind than by a corresponding set with the 
currents still more feeble, that increase, while acting, the frequency of the 
contractions. But if the diminished rate of the pulsations were caused by 
a partial exhaustion of the cardiac ganglia, an opposite result might have been 
anticipated. 

Again, there can be little doubt that dilatation of the blood-vessels, in 
consequence of a stimulus, is due to an effect produced upon the nervous centres 
for the arteries, similar to that experienced by the visceral ganglia when subject 
to the inhibiting influence. Now an inflammatory blush of long continuance 
may subside rapidly when the source of irritation is withdrawn. Thus I have 
seen redness which had existed for about three days in the human skin in con- 
sequence of tight stitches connecting the lips of a wound, give place at once 
to pallor on their removal. Had the arterial dilatation in this case been the 

* Henle and Meissner’s Bericht, 1857. 


LISTER I H 


98 AN INQUIRY INTO THE FUNCTIONS OF THE VISCERAL NERVES 


result of nervous exhaustion continued during so long a period, such speedy 
recovery could hardly, one would think, have taken place. 

These and other considerations, to which the already excessive length of 
this letter forbids me to allude, induce me to think it safest in the present state 
of science to regard as a fundamental truth not yet explained, that one and 
the same afferent nerve may, according as it is operating mildly or energetically, 
either exalt or depress the functions of the nervous centre on which it acts. 
It is, I believe, upon this that all inhibitory influence depends, and I suspect 
that the principle will be found to admit of a very general application in 
physiology. 


1 amnecc: 


JosEPH LISTER. . 


SOME OBSERVATIONS ON THE STRUCTURE 
OF NERVE-FIBRES 


WRITTEN IN COLLABORATION WITH WILLIAM TuRNER}?, Esq., M.B., Lond., 


Senior Demonstrator of Anatomy in the University of Edinburgh. 


[Quarterly Journal of Microscopical Science, October 1859.] 


HAVING recently had the opportunity, through the kindness of Mr. Lockhart 
Clarke, of inspecting some of his beautiful preparations of the spinal cord, we 
were struck with an appearance which had not yet received a satisfactory inter- 
pretation; and, having been induced to investigate the point, we have met 
with some facts which seem of sufficient interest for publication. 

For the sake of clearness it may be well to state briefly the method employed 
by Mr. Clarke in preparing his specimens. 

A portion of perfectly fresh spinal cord having been hardened by steeping 
in dilute chromic-acid solution, thin sections are made with a razor, and these, 
after immersion for a while in an ammoniacal solution of carmine, are soaked 
in spirits of wine to remove the water, and then treated with oil of turpentine. 
The last-named agent has the effect of rendering the sections transparent, so 
that the nerve-cells of the grey matter, finely coloured by the carmine, are seen 
with the utmost distinctness, giving off in various directions long branching 
processes ; while the nerve-fibres, which are similarly tinted, may be traced 
with equal facility in their course through the cord. 

In the preparations which we saw, the cord had been sliced crosswise, and 
in the columnar regions, where the nerve-fibres have for the most part a longi- 
tudinal direction, the transverse section of each fibre showed itself as a carmine- 
coloured point, surrounded by a perfectly pellucid and colourless ring. This 
was the appearance which seemed to demand explanation, the question being 
whether the transparent ring was a mere space, resulting from shrinking of the 
object during the preparation, or the white substance of Schwann (medullary 
sheath) rendered transparent by the turpentine, the axial cylinder alone, in that 
case, having received the carmine colour. 

It occurred to us that the point might probably be determined by applying 
a similar mode of preparation to some nerve the dimensions of whose fibres could 
be readily ascertained. With this view we steeped in chromic acid portions 
of the sciatic nerve of a cat just killed, and also parts of the spinal cord of the 

* Now(1908) Sir William, K.C.B., F.R.S., Principal and Vice-Chancellor of the University of Edinburgh. 
se 


100 SOME OBSERVATIONS ON THE 


same animal; and having allowed them to remain between three and four 
weeks in the solution, we commenced the investigation in July of the present 
year, 1859. 

A transverse section of the hardened sciatic nerve having been placed for 
a time in the carmine solution and then dried, we submitted it, without the 
application of turpentine, to microscopic examination with a power of 130 dia- 
meters. Viewed by transmitted light, it appeared as a confused opaque mass ; 
but, by reflected light, it exhibited the structure depicted in Plate IV, Fig. 1, 
each nerve-fibre presenting in its section a carmine spot, surrounded by a yellow- 
ish-white, somewhat granular ring, which, though doubtless corresponding to 
the pellucid rings in the preparations of the cord before alluded to, was clearly 
composed of some solid material, in short, of the white substance of Schwann 
altered by the action of the chromic acid. 

We next examined sections of the cord treated in the same way, but found 
that these dry specimens were so incrusted with carmine that they gave no 
definite results. It happened, however, that one of the sections treated with 
carmine still remained moist, and, after washing away all superfluous colouring 
matter, we examined it by transmitted light. A very beautiful appearance 
now presented itself, carmine points being seen in the columnar regions, as 
in Mr. Clarke’s preparations, surrounded by rings; but the latter, instead of 
being transparent like mere spaces, were dead white; the carmine points, on 
the other hand, appearing in the thinnest parts of the section as illuminated 
spots amid the general opacity. This is represented in Fig. 5. 

It will be seen from this sketch, which is drawn on the same scale as Fig. 1, 
that the nerve-fibres varied very much in their diameter, the largest being of 
about the same size as those of the sciatic nerve, while others were of extreme 
minuteness ; but in all cases in which they were sufficiently large to be dis- 
tinguished, they had the same character of a white circle with a central carmine 
spot from one-fourth to one-third the diameter of the whole fibre. It was 
obvious that, in the cord, as in the sciatic nerve, the carmine central part of 
each fibre was the axial cylinder, and the opaque circumferential portion the 
medullary sheath ; and, therefore, that the pellucid rings in preparations treated 
with turpentine consisted of the white substance rendered transparent by that 
reagent. 

The point at issue was thus satisfactorily decided; but for the sake of 
confirmation we made some further observations, the results of which seem 
deserving of mention. 

On examining the hardened sciatic nerve, without tinting the preparations 


* This sketch, like the others illustrating this paper, was drawn by means of the camera lucida. 


STRUCTURE OF NERVE-FIBRES IOI 


with carmine, we found that in extremely thin slices the transverse sections 
of the nerve-fibres, viewed by transmitted light, appeared as brownish rings 
with central transparent colourless spots (see Fig. 3), whilst by reflected light 
the central parts appeared black, as shown in Fig. 2. In fact, under a low 
power the axial cylinders had, in these specimens of the sciatic nerve, as much 
the appearance of mere spaces as the medullary sheaths had in preparations 
of the cord treated with turpentine. But on applying a fine glass of high power 
a granular appearance was disclosed in the pellucid central portion, showing 
that it was in reality a solid substance, though of a transparency which was 
very remarkable, considering that it had been so long subjected to the action 
of chromic acid; and on afterwards treating similar sections with carmine we 
found that this part alone became coloured. The higher magnifying power 
also brought out an appearance of irregular concentric lines in the brown! 
medullary sheath; and this, together with the granular aspect of the axial 
cylinder, is represented in Fig. 4. 

These facts afford a very striking illustration of the essential difference 
in chemical composition between the axial cylinder and the medullary sheath, 
the former being totally unaffected by chromic acid, though the latter is rendered 
opaque and brown and concentrically striated under its influence, while, on 
the other hand, the axial cylinder, after being subjected to the action of chromic 
acid, imbibes the carmine colour with peculiar facility, although the medullary 
sheath is entirely untinged by it. 

We next applied the high magnifying power to extremely thin slices of 
the spinal cord preparedin thesame way. In transverse sections of the columnar 
regions the white substance of Schwann presented, in the larger fibres, the same 
concentrically arranged appearance as we had observed in the sciatic nerve, 
as is illustrated by Figs. 6 and 7, of which Fig. 6 is one of the largest met with, 
being 1-gooth of an inch in diameter, while Fig. 7 is as small as 1-3000th of an 
inch in transverse measurement. In the very minute fibres no appearance of 
concentric lines could be detected, yet, wherever the existence of an axial cylinder 
was indicated by a carmine point, a ring of medullary sheath was always visible, 
presenting the same proportion to the axial cylinder as in fibres of larger size. 
This may be gathered from Figs. 8, 9, and ro, of which Fig. 8 measures 1-5000th 
of an inch across, Fig. 9 1-800o0th, and Fig. ro only 1I-r4oooth. 


1 It must be mentioned that a similar brown colour is seen in the superficial parts of a cord which 
has been steeped in chromic acid, but the deeper portions of the organ are comparatively only slightly 
coloured, so that in individual nerve-fibres seen under a high magnifying power the brown tint is not 
observed. 

* In a boiled fresh nerve also the medullary sheath remains unaffected by ammoniacal solution 
cf carmine, while the axial cylinder assumes a distinct though very faint pink tint.—J. L. 


102 SOME OBSERVATIONS ON THE 


At the margins of longitudinal sections of the cord, the contrast, both in 
structure and in tint, between the axial cylinder and the medullary sheath 
showed itself very beautifully. It often happened that a projecting isolated 
fibre was, near its extremity, more or less divested of the white substance of 
Schwann, so that the delicate, carmine-tinted axial cylinder was exposed, though 
presenting here and there colourless flakes of the medullary sheath adhering to 
its surface, while in parts where the nerve was still entire, the pink colour 
of the central fibre could be distinctly discerned through the intervening white 
substance. Fig. 11 represents a large fibre under such circumstances, and 
Fig. 12 one of considerably smaller size ; and these sketches also display the 
remarkable fibroid arrangement which we find the white substance of Schwann 
invariably assumes under the influence of chromic acid. 

In conclusion, we may remark that the successive employment of chromic 
acid and carmine seems likely to afford valuable aid in discriminating nerve- 
fibres among other structures, there being, so far as we are aware, no other 
form of tissue which, after the use of these means, exhibits fibres having a central 
carmine axis and peripheral uncoloured sheath. 


Supplementary Observations by Mr. LISTER 


The fibroid arrangement of the white substance of Schwann in nerves 
hardened by chromic acid has been minutely described by Stilling, in his 
elaborate treatise on the ‘ Nerve-fibre and Nerve-cell’,! a work which we had 
not seen when the foregoing communication was written, but a copy of which was 
kindly lent me by Professor Goodsir, soon after Mr. Turner had left Edinburgh 
for the vacation. According to Stilling, the medullary sheath is, even in per- 
fectly fresh nerves, composed of a network of fibres, which are continuous 
with others in the axial cylinder and in the proper investing membrane; so 
that, in his opinion, these three constituents of the nerve-fibre differ from each 
other only in the manner in which their elements are disposed.2 This view 
is not only quite novel anatomically, but is opposed to the generally received 
physiological opinion, that the axial cylinder is the essential part of the nerve- 
fibre, and the medullary sheath an insulating investment. Considering the 
high estimation in which the writings of Stilling on the anatomy of the nervous 
centres are deservedly held, and the influence which therefore attaches to his 
opinions, it seems fortunate that we have been able to present so clear a demon- 
stration that the axial cylinder is chemically as well as morphologically totally 
distinct from the medullary sheath. 


* Ueber den Bau dev Nerven-Primitivfaser und der Nervenzelle. Won Dr. B. Stilling. 1856. 
ERO. /Cits, (P. °6 


STRUCTURE OF NERVE-FIBRES 103 


With regard to the cause of the fibroid arrangement of the medullary 
sheath, an observation which I happened to make several years ago, regarding 
the aggregation of fatty matter, may perhaps tend to throw light upon the 
subject. I submitted to microscopic examination some of the pultaceous 
slough of a sore affected with hospital gangrene, thinking it possible that I might 
discover in it some fungus which might account for the peculiar specific character 
of that disease; and found in it numerous bodies, each composed of branching 
fibres radiating from a common centre, and looking, at first sight, like some 
sort of vegetable growth, so that I made careful sketches of them, one of which 
is reproduced in Fig. 13. But seeing afterwards, in the same object, some 
bundles of acicular crystals of margarine having a distant resemblance to the 
bodies I had drawn, J added ether to the specimen, and found that it dissolved 
the latter equally with the former. This showed that what first attracted my 
attention was merely an arborescent form of aggregation of some fat, probably 
margarine ; and it seems not unlikely that the fluid fat which exists in the 
medullary sheath of a perfectly fresh nerve may tend to a similar arrangement 
of its particles when passing into the solid form, and so give rise to the appear- 
ance in question. It is to be remarked that the fibroid character is not peculiar 
to specimens treated with chromic acid, but also shows itself, though in a less 
perfect manner, in nerves which have been subjected to other modes of prepara- 
tion—for example, after exposure for a few seconds to a temperature of 212° Fahr. 

There is another important statement made by Stilling, which the use of 
the method of examination above described enables me to correct. He speaks 
of the fibres which connect one nerve-fibre with another as similar in every 
respect to those seen in the medullary sheath. I find, however, that both in 
the sciatic nerve and in the spinal cord of the cat, the connective tissue between 
the nerve-fibres, like the neurilemma and pia mater, with which it is con- 
tinuous, becomes coloured by the carmine; whereas, the medullary sheath, as 
before stated, is quite unaffected by it, proving that the two structures are 
chemically distinct from one another. In both these situations, too, the fibres 
of the connective tissue are much more delicate than the constituents of the 
medullary sheath, which are often comparatively coarse, as may be seen from 
Fig.11r. In the columnar regions of the cord, the former require a high magnify- 
ing power to be applied to very thin sections, in order to distinguish them, 
and are often present in such extremely small quantity that, without very 
careful examination, the nerve-fibres appear actually in contact with one another. 
In the sciatic nerve I have observed occasional elongated nuclei in the con- 
nective tissue. 


Op xcit.. Pugs 


104 SOME OBSERVATIONS ON THE STRUCTURE OF NERVE-FIBRES 


I may add that glycerine has proved very useful, not only for permanently 
preserving the preparations in the moist state, but also as an aid to investigation; 
for it renders the sections much more transparent, without making the white 
substance of Schwann invisible, as turpentine does; and hence the course of 
the nerve-fibres through the cord can be traced much more easily, and, at the 
same time, the proportion between the medullary sheath and axial cylinder can 
be readily ascertained. Thus, by examining transverse sections of the cord in 
this way, I find that while KGlliker is quite correct in his statement that the 
fibres of the roots of the nerves diminish in size in passing inwards through 
the columnar regions,’ yet the diminution affects only the white substance, 
the axial cylinder often retaining its full dimensions even in the middle of the 
grey matter, while the medullary sheath is reduced to a very thin crust, so that 
the nerve-fibre assumes a character differing but little from that of an offset 
of a nerve-cell. 


* KOlliker’s Handbuch der Gewebelehre, 3rd ed., p. 285. 


DESCRIPTION OF BEATE AV 


Fig. 1 represents part of a transverse section of the sciatic nerve of a cat hardened by chromic acid, 
and tinted with carmine, the axial cylinder alone having received the colouring matter. The 
specimen was dried and viewed as an opaque object. 


Fig. 2 shows the appearance of thin transverse sections of some nerve-fibres from the same nerve, simply 
hardened in chromic acid, and examined moist by reflected light. The axial cylinder has, under 
this low magnifying power, the aspect of a mere space. 


Fig. 3, similar objects to those of Fig. 2, but seen by transmitted light. 


Fig. 4, a highly magnified transverse section of a nerve-fibre from the same source, prepared like those 
of Figs. 2 and 3, and then tinted with carmine. The carmine colour is seen to affect only the 
axial cylinder and the investing membrane, which, at one part, is torn up from the fibre. This 
sketch also shows the faintly granular structure of the axial cylinder, and the irregularly concentric 
striation of the medullary sheath. 

Fig. 5, a transverse section of a columnar portion of the spinal cord of a cat, also prepared with chromic 
acid and carmine, and examined moist by transmitted light. The fibres vary much in size, but 
all of them resemble those of the sciatic nerve in having the red axial cylinder surrounded by 
a ring of untinted medullary sheath. 

Figs. 6-10 are highly magnified views of some fibres in a section of the cord like that of Fig. 5. They 
present the same characters as the fibres of the sciatic nerve. 

Fig. 11, a fibre from a longitudinal section of a columnar portion of the cord, prepared in the same way 
The axial cylinder alone is carmine coloured, and is, in some parts, stripped of its investing sheath, 
the fibroid arrangement of which is also displayed. 

Fig. 12, a small fibre under similar circumstances. 


Fig. 13, fatty matter in a state of arborescent fibroid aggregation. 


Plate |V 


ae Ae {e & 
te S ZAG] ELL 
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NOVICE, OF FURTHER RESEARCHES ON THE 
COAGULATION OF THE BLOOD 


Read before the Medico-Chirurgical Society of Edinburgh, November 16, 1859. 


[Edinburgh Medical Journal, December 1859.] 


Mr. PRESIDENT.—I take this opportunity of demonstrating what appears 
to be a point of considerable importance with reference to the coagulation of 
the blood—a subject to which my attention has been again directed by the 
recurrence of that period of the Session in which the fundamental principles 
of pathology are discussed in a course of surgical lectures. 

I may remind the Fellows of this Society, that in a paper which I had the 
honour to read before them the Session before last,! I brought forward facts 
which seemed to prove that the ammonia theory does not apply to blood within 
the vessels of a living animal. That theory, as my hearers are doubtless aware, 
asserts that the fluidity of the blood depends upon the presence of a certain 
amount of free ammonia holding the fibrine in solution, and that coagulation 
is the necessary result of the escape of the volatile alkali. But it was shown 
in the paper referred to, that the blood, in man and other mammalia, though 
coagulating soon after death in the heart and great venous trunks, remains 
fluid for days in vessels of smaller size, and this under circumstances affording 
free opportunity for the escape of ammonia; and, on the other hand, that 
when a portion of a vessel either in an amputated limb or in a living animal 
is treated in a manner calculated to destroy its vital properties, the blood 
coagulates in the injured part, but retains its fluidity elsewhere, although there 
is no greater opportunity for the escape of ammonia in the one case than in 
the other. A striking instance of the difference between the natural receptacles 
of the blood and ordinary matter in their relations to the vital fluid happened 
to come under my notice this morning, in an arm which I amputated last evening 
at the shoulder-joint, on account of injury inflicted by machinery. On examin- 
ing the limb, which had lain undisturbed since the operation, I saw that the 
axillary vein, which was patulous at the part where it had been divided by 
the knife, contained some blood at a distance of about half an inch from the 
open orifice ; and having squeezed out a few drops, found that it was perfectly 
fluid, but yielded threads of fibrine when the point of a needle was drawn through 
it some minutes after emission. The blood had been for upwards of twelve 

* Vide Edinburgh Medical Journal, April 1858 (p. 69 of this volume). 


106 NOTICE OF FURTHER RESEARCHES 


hours freely exposed to the air, but being situated in an uninjured part of a 
blood-vessel, had remained free from coagulation. 

Further, in the opening meeting of last Session I demonstrated another 
important principle, viz.—That ordinary solid matter, unlike atmospheric air, 
induces coagulation of blood in its vicinity when introduced within the living 
vessels. Having inserted a piece of clean silver wire for a considerable distance 
into one of the veins of an amputated sheep’s foot, I slit up the vessel after 
a short time had elapsed ; when I exhibited a coagulum extending along the 
whole length of the foreign body, whereas a mere wound of the vein failed to 
induce a clot except immediately at the spot where the injury had been inflicted. 
It was obvious that the introduction of the wire could not affect the amount 
of ammonia in the blood; and from this and many other facts, to which I need 
not here allude,t I was led to the opinion, that as regards what takes place 
within the living vessels, the ammonia theory might practically be left entirely 
out of consideration. 

What I have to show this evening will, I think, prove that even for blood 
outside the body, the ammonia theory, whatever degree of truth it may contain, 
is very far indeed from representing the whole truth. 

One of the most remarkable circumstances connected with blood that has 
been shed from the vessels is, that it refuses to coagulate below a temperature 
of 40° Fahr. or thereabouts. This is explained by Dr. Richardson on the hypo- 
thesis that the low temperature prevents the evolution of ammonia,’ while 
the rapidity with which coagulation takes place at high temperatures seems 
to him satisfactorily accounted for by the increased volatility exhibited by the 
ammonia under such circumstances. I was myself at first disposed to accept 
this interpretation, but subsequent reflection led me to think that, to say the 
least, it required confirmation. It occurred to me that if it were true that the 
fluidity of blood below 40° was due to free ammonia retained in it, coagulation 
would take place immediately, in spite of the cold, if the alkali were neutralized 
by the addition of acid, provided the fibrine were not impaired in its coagu- 
lating property by the reagent employed. In order to ascertain whether this 
result would really follow, I poured blood freshly shed from a sheep into vessels 
surrounded by ice-cold water, and by this means succeeded in keeping some 
portions of it fluid for a considerable time, and found that it continued liquid 
notwithstanding the addition of dilute acetic acid in what I supposed must be 


* For some of these facts see ‘On the Early Stages of Inflammation,’ Philosophical Transactions 
for 1858, pp. 673, et seq. 

* See Dr. Richardson’s Astley Cooper Prize Essay, p. 303, where a fact is mentioned, indicating 
that no ammonia was given off at 34° Fahr. from a specimen of blood which had been artificially am- 
moniated, and which at 96° afforded distinct evidence of evolution of the alkali. 


ON THE COAGULATION OF THE BLOOD 107 


sufficient quantity to overcome the feeble alkalinity of the blood, while the 
acidulated specimen retained the property of coagulating very rapidly when 
raised in temperature. But on attempting to discover whether this blood was 
really acid in reaction, I found that its red colour entirely vitiated the indications 
of both litmus and turmeric; and even the serum obtained after contraction 
of the clot was too much tinged to admit of the satisfactory application of the 
test-paper. 

| Being thus baffled in my experiments with the sheep, I had recourse to the 
horse, in which the red corpuscles subside with peculiar rapidity in the plasma, 
giving rise to the buffy coat well known to occur in the blood of that animal 
in the state of health, so that the opportunity would be presented of obtaining 
liquor sanguinis free from red corpuscles, to which the tests could be applied 
without risk of fallacy. Accordingly, yesterday afternoon, a horse having been 
placed at my disposal by my friend Mr. Gamgee of the New Veterinary College, 
I tied into the right jugular vein one end of a piece of vulcanized india-rubber 
tube, four yards in length, the greater part of which was coiled up in a freezing 
mixture, and some of the blood, having been allowed to remain for a while in 
the tube, was shed into vessels standing in ice-cold water. Its temperature 
on first escaping into the air was 39$° Fahr., and having been since kept in 
the cold it is still only partially coagulated at the present time (twenty-nine 
hours after it was shed). At first, however, it appeared as if we were likely 
to fail, the blood of this horse being a rare exception to the general rule, in 
exhibiting for a long time no appearance of the ‘sizy’ layer. But after it had 
stood for about two hours, I succeeded in removing from the surface, by means 
of a glass tube, a sufficient amount of liquor sanguinis for the performance of 
an experiment, taking care that the glass into which it was shed, and the tube, 
were both near the freezing-point. To half a drachm of this plasma I now 
added one minim and a half of moderately dilute acetic acid, which had the 
effect of rendering it distinctly acid, as indicated by its communicating a red 
tint to litmus and restoring the colour of turmeric paper which had been 
reddened by dipping it in the portion of the hquor sanguinis which had not been 
acidulated. I kept the specimen in ice-cold water till this evening. For a long 
time it remained perfectly fluid, except the formation of little soft coagulum 
at the surface, just as in the unacidulated blood; but a few drops placed in 
a watch-glass and brought into a warmer atmosphere, coagulated in about the 
same time as the blood that first flowed from the tube, a soft clot forming in 
about a quarter of an hour. Even at the expiration of twenty-four hours a 
portion of what remained in the cold was still fluid, though faintly acid, but 
set into a pretty firm clot on being removed into a warmer situation. 


108 FURTHER RESEARCHES ON COAGULATION OF THE BLOOD 


‘Mr. Lister now proceeded to perform a similar experiment before the 
Society. A glass containing some liquor sanguinis of the horse’s blood, shed 
twenty-nine hours before, was taken out of the mixture of ice and water in 
which it stood, and the contents were seen to be still to a considerable extent 
fluid, although acidulated with acetic acid two hours previously. A portion of 
the liquid was poured into a watch-glass, and, having been shown to be acid by 
litmus paper, was set aside to coagulate, and about a quarter of an hour later 
was exhibited as a soft clot. Mr. Lister then continued :—] 

From these facts it is obvious that the ammonia theory utterly fails to 
explain the influence of temperature on coagulation. The circumstance that 
the liquor sanguinis was acid in this experiment is clear proof that it contained 
no free ammonia whatever, yet the acidulated plasma was affected by cold 
and heat, just like ordinary blood. It remained fluid near the freezing-point, 
although the ammonia it originally contained must have entered into com- 
bination and lost its reputed power of dissolving the fibrine, and it coagulated 
when warmed, though the ammonia, fixed by the acid, must have been incapable 
of evolution. If the author of the ammonia theory were asked to explain why 
this horse’s blood took a quarter of an hour to coagulate, he would no doubt 
reply that it must have contained a large amount of ammonia, requiring all 
this time to escape. But we have seen that the acid liquor sanguinis, though 
possessing no free ammonia at all, took as long to clot. There can therefore 
I think be little question but that the slowness of coagulation in the horse, 
compared with the rapidity of the process in the sheep, and the variations met 
with in the period in the human species, depend not on the amount of ammonia 
present in the blood, but on differences in its other constituents, and, speaking 
generally, that the theory which attributes the coagulation of the blood to the 
escape of ammonia is fallacious." 


* Since the above communication was made, I have seen for the first time the able essay of 
Dr. E. Briicke, which competed for the Astley Cooper Prize (see Med.-Chir. Review, vol. xix); and 
I find that the principle which he advocates—viz. that the fluidity of the blood within the living body 
depends upon an action of the walls of the vessels upon it—is supported by many facts which he has 
observed in the chelonian reptile, very similar to what I have made out in mammalia. Thus, he found 
that the blood remained fluid in the heart of the turtle for days after death, and for several hours after 
he had blown air through the veins of the neck, so as to make a foamy mixture in the cavities of the 
organ. He also found, as had been previously ascertained by Virchow and others, that after the intro- 
duction of mercury into the heart the blood coagulated about the globules of the metal, but not 
elsewhere, and this he regarded as an example of the influence of ordinary matter in inducing coagula- 
tion in its vicinity. He also succeeded with the following very striking experiment, which would not have 
answered with mammalia: he drew blood into a cup from the veins of a living turtle, and injected it 
into the empty heart of another turtle just killed, and found that the blood remained fluid for several 
hours in its new situation, instead of coagulating in a few minutes as when retained in a cup.—J. L. 


i 


ONT REE COAGULATION OF THE “BLOOD 


THE CROONIAN LECTURE 


Delivered before the Royal Society of London, June 11, 1863. 


[Proceedings of the Royal Society of London, 1863.] 


THE subject on which I have the honour to address you this evening is 
one which lies at the foundation both of Physiology and Pathology, and, on 
account of its great importance, has engaged the best energies of many very 
able men, among whom may be mentioned, for example, such distinguished 
Fellows of this Society as John Hunter and Hewson; so that it might well 
seem presumptuous in me to hope to communicate anything new regarding it, 
were it not that the constant progress of Physiology and the allied sciences 
is ever opening up fresh paths for inquiry, and ever affording fresh facilities for 
pursuing them. Indeed, my difficulty, on the present occasion, does not depend 
so much on the lack of materials as on the complicated relations of the subject, 
which make me almost despair of being able, in the short time that can be de- 
voted to a lecture, to give, in anything like an intelligible form, even an adequate 
selection of the facts at my disposal. 

It may, in the first place, be worth while, more especially for the sake of 
any present who may not be physiologists, to mention very briefly some well- 
known general facts respecting the constitution of the blood. The blood, if 
examined by the microscope within the vessels of a living animal, is seen to 
consist of a liquid and numerous small particles suspended in it. The liquid 
is termed the ‘ liquor sanguinis ’, the particles the ‘ blood-corpuscles’. Of these 
corpuscles a few are colourless, and are named the ‘ colourless’ or “ white cor- 
puscles’. The great majority are coloured and cause the red appearance of 
the blood, and hence are called the ‘red corpuscles’. Soon after blood has 
been shed from the body, it passes from the fluid into the solid form. This 
depends upon the development in the blood of a solid material termed ‘ fibrine’, 
so called from its fibrous nature, consisting, as examined by the naked eye, of 
tenacious fibres, and having the same character also under the microscope. 
These fibres form a complicated network among the blood-corpuscles, and from 
their tenacity are the cause of the firmness of the clot. Soon after the process 
of solidification or coagulation is complete, the fibrine exhibits a disposition to 


IIO ON THE COAGULATION OF THE BLOOD 


shrink, and squeezes out from among the corpuscles entangled in its meshes 
a straw-coloured fluid termed the serum, very rich in albumen, in fact very 
similar in chemical composition to the fibrine, which, in its turn, may be said 
to be identical chemically with the material of muscular fibre. 

The question before us, therefore, is, What is the cause of the development 
of this solid material, the fibrine ? The subject may be looked at in two aspects— 
first, as to the essential nature of the process of coagulation ; and secondly, as 
to the cause of its occurrence when the blood is removed from the body. 

With regard to the first point, the essential nature of the process of coagula- 
tion, different views have been entertained. John Hunter was of opinion that 
the coagulation of the blood, the solidification of the fibrine, was an act of life— 
analogous, in some respects, to the contraction of muscular fibre. This, on the 
other hand, was made very unlikely by the observation of his contemporary, 
Mr. Hewson, that blood may be kept in the fluid state by the addition of various 
neutral salts, but retains the faculty of coagulating when water is added to the 
mixture. Mr. Gulliver, on one occasion, kept blood fluid, by means of nitre, 
for upwards of a year, but found that it still coagulated on the addition of water. 
It seems exceedingly improbable that any part of the human body should retain 
its vital properties after being thus pickled for more than a year. But here 
I would wish to make an explanation of the use of this term ‘ vital properties ’. 
When employing it, I do not wish to commit myself to any particular theory 
of the nature of life, or even to the belief that the actions of living bodies are 
not all conducted in obedience to physical and chemical laws. But it appears 
that every component tissue of the human body has its own life, its own health, 
just as we ourselves have; and as the actions of living men will ever retain 
their interest whatever views be entertained of the nature of life, so must the 
actions of the living tissues ever continue to be essential objects of study to 
the physiologist and pathologist. When, therefore, I use the term ‘ vital pro- 
perties ’, I mean simply properties peculiar to the tissues as components of the 
healthy living body. 

Turning now to the other aspect of the subject of coagulation—the cause 
of the occurrence of that process on the escape of the blood from the living 
body—we find that here again various theories have been held, which may 
be divided into mechanical, chemical, and vital. The mechanical theory was, 
that mere rest of the blood was sufficient to cause coagulation. I say this was 
the theory ; but I believe it will be found to be still taught by many that the 
cause of the coagulation of the blood in an artery which has been tied is its 
stagnation in the vicinity of the ligature. 

As to the chemical theories they have been various. One very natural 


ON THE COAGULATION OF -THE BLOOD sO) 


view was that exposure to the air was the essential cause of coagulation. Mr. 
Hewson believed that this was, at all events, an important element in the causes 
of the phenomenon; and many eminent physiologists and pathologists have 
held the same view, except that, instead of the air as a whole, the oxygen of 
the air has been supposed to be the important element. 

Sir Charles Scudamore considered that coagulation was greatly promoted 
by the escape of carbonic acid; and more recently the evolution of ammonia 
has been regarded as the essential cause of the change. According to the 
ammonia theory, due to Dr. Richardson of this city, the fluidity of the blood 
within the body depends on a certain amount of free ammonia holding the 
fibrine in solution, and the coagulation of the blood when withdrawn from the 
vessels is the result of the escape of the volatile alkali. 

Then, as to vital theories. These have been held by many physiologists, 
among whom may be mentioned Sir Astley Cooper and Mr. Thackrah, who, 
from experiments which they performed, were led to the inference that the 
living vessels exert an active influence upon the blood, by which coagulation 
is prevented ; and Mr. Thackrah went so far as to attribute this action of the 
vessels to nervous influence. The view that the blood is kept fluid by the 
operation of its natural receptacles has been advocated more recently by Briicke 
of Vienna, whose essay will be found in the British and Foreign Medical Review 
for 1857. Briicke performed his experiments on turtles and frogs, in which 
animals the blood remains fluid in the heart for days after death ; and I feel 
bound to say that some of the facts which he has brought forward seem to me 
quite sufficient to show that the ammonia theory, whatever amount of truth 
it may contain, cannot be the whole truth, and cannot explain the fluidity of 
the blood within the body. For example, Briicke found that, having shed 
blood from the heart of a living turtle into a basin, and transferred, with a 
syringe, a portion of that blood into the empty heart of another turtle just 
killed, the blood thus transferred into the empty heart remained fluid for hours, 
whereas that which was left in the basin coagulated in a few minutes. He 
also found that blood continued fluid in the heart of a turtle long after the 
injection of air into the heart through a vein till the cavities of the organ con- 
tained a foamy mixture of blood and air. 

Yet it by no means follows that the vital theory and the ammonia theory 
are necessarily altogether inconsistent. It might be true for anything we could 
tell, a priort, that the coagulation of the blood, when shed from the body, might 
depend on the evolution of a certain amount of ammonia, previously holding 
the fibrine in solution, and yet it might, at the same time, be true that the cause 
of the ammonia remaining in the blood in the healthy vessels might be an action 


132 ON THE COAGULATION OF THE BLOOD 


of the living vessels retaining it there. It might be that an action of the living 
vessels might chain down the ammonia and prevent it from escaping, whereas, 
when shed from the body, it would be free to escape. 

This notion was, I confess, at one time entertained by myself; and one 
of my earliest experiments was performed with a view to the corroboration 
of the ammonia theory as applied to blood outside the body. It seemed to 
me desirable that further evidence should be afforded of the effect of mere 
occlusion from air in maintaining the blood fluid. If the ammonia theory 
were true, then if blood could be shed directly from a living vessel into an air- 
tight receptacle composed of ordinary matter it ought to remain fluid. For 
this purpose, I made the following experiment :— 
I tied into the jugular vein, V (Fig. 1), of a sheep 
a long vulcanized india-rubber tube, T, adapted 
by means of short pieces of glass tube at its 
extremities, both ends being connected with the 
vessel so that the current of blood might be per- 
mitted to flow through the tube, and then con- 
tinue its natural course. When it had been 
ascertained that the blood was circulating freely 
through the tube, which could be readily done 
by placing the finger on the cardiac aspect of the 
vein, which was then made to swell if the circula- 
tion was proceeding through the tube, pieces of 
string well waxed were tied at intervals of about 
two inches round the tube, which was thus 
converted into a number of air-tight receptacles containing blood, which 
certainly had no opportunity for the escape of ammonia. The tube was then 
removed, and I found, in accordance with the view which I was then disposed 
to entertain, that the blood, instead of coagulating completely in a few minutes 
as it would have done if shed into a cup, remained partially fluid in these recep- 
tacles after the lapse of three hours. But I have since found that if the experi- 
ment be repeated in the same way as regards its earlier stages, and if, after 
a few of the strings have been tied on, the tube be cut across, the blood which 
is in the part of the tube in the vicinity of the air, just like that which is in the 
air-tight receptacles, remains fluid in part for two or three hours. In short, 
that my precautions in ensuring that these receptacles should be air-tight were, 
in so far as they applied to that object, utterly unnecessary. I mention this 
partly as an illustration of the deceptions to which one is liable in this inquiry, 
and partly because the experiment thus modified seems to tell as clearly against 


FIG. I. 


ON THE COAGULATION OF THE BLOOD 113 


the ammonia theory as the original one seemed to tell in favour of it. Those 
receptacles which had been formed by the application of ligatures before the 
tube was opened afforded certainly no opportunity for the escape of ammonia, 
and yet in them the blood coagulated as quickly as in those which had com- 
munication with the air—implying that facility for the evolution of ammonia 
does not in itself affect the process of coagulation at all. 

How then, it may be said, is the persistent fluidity of the blood under 
these circumstances to be explained? That will become more obvious than 
I can make it at present in the sequel, but in the 
meantime I may observe that there are probably ez 
two explanations: one is, the coolness of the tube, 
and the other, far more important, that the blood, 
in slipping through this cylindrical tube, had had 
little opportunity of being influenced by its walls. 
The portion of the blood that came first in contact 
with the walls of the tube had coagulated ; and it 
is to be observed that I never found, in these ex- 
periments, the blood altogether fluid, even after a 
comparatively short time: there has always been 
a certain amount of coagulation, and only a certain 
amount of fluidity. A layer of blood having thus 
coagulated upon the internal surface of the tube, 
the fresh blood, which continued to flow through it, 
was not brought into contact with the walls of the 
tube at all, but with their lining of coagulated 
blood. 

It has been long known that if blood is stirred 
with a rod, the process of coagulation is promoted. 
It seemed desirable to ascertain distinctly whether 
the cause of this was the contact of the foreign 
solid, or the opportunity given for the escape of ammonia ; for it is quite true 
that, in the ordinary process of stirring blood, more or less air is mixed with it. 
For the purpose of determining this I devised a somewhat complicated experi- 
ment, which, however, it may be worth while to mention. I madean apparatus 

(Fig. 2) of two portions of glass tube, A and B, connected in a vertical position 
by means of vulcanized india-rubber, I, the lower portion of the glass tube being 
also connected by india-rubber, I’, with a wooden handle, which handle, H, was 
provided with an upright piece of wire, from which spokes projected in different 
directions, so that they would, when moved, act asa churn on any blood contained 


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114 ON THE COAGUTALION OF THE BLOOD 


in the lower portion of tube. When the lower piece of tube was fixed by mean of 
a vice, V, the flexibility of the india-rubber permitted the churn to be rotated so 
as to expose the blood to its influence. This having been arranged, I first poured 
in strong liquor ammoniae, so as to get rid of any slight acidity which the con- 
stituents of the apparatus might be conceived to possess, and then, having poured 
out the ammonia, filled up the apparatus with water, and boiled the whole in 
a large glass test-tube till all bubbles of air, in any portion of it, were expelled. 
Having then tied into a branch of the carotid artery, C, of a calf a bent tube of 
small diameter, as represented, and having permitted the blood to flow till it 
escaped at the orifice of the tube, I compressed the artery and passed the tube 
down through the water to the bottom of the apparatus, and then let the blood 
flow again, which had the effect of displacing all the water; and when the 
blood appeared at the top of the apparatus, the tube was withdrawn, when two 
effectual clamps, Cl, Cl, were placed on the vulcanized india-rubber connecting 
A and B; the india-rubber was then divided between the clamps, and we had 
the state of things represented at the right-hand side of the diagram. The 
upper portion of the apparatus, the orifice of which was exposed to the air, 
was set aside and left undisturbed. Having ascertained that the lower portion 
had been effectually sealed by the clamp, and thus prevented from any oppor- 
tunity of escape of ammonia, I subjected it to the action of the churn for a 
certain number of minutes. It so happened that the blood of that calf was 
very slow in coagulating. I knew this from previous experiments on the animal, 
and therefore continued the action of the churn for a considerable time, viz. 
thirty-seven minutes. I then found the wire enveloped in a mass of clot ; 
and examination of the fluid residue with a needle indicated that the fibrine had 
been all withdrawn from the blood on which the churn had acted. I did not 
now examine the other portion of the apparatus, which had been set aside, 
but at the end of an hour and a quarter, when more than double the time had 
elapsed, I investigated this, and found the blood in it, for the most part, still 
fluid and coagulable. Thus the blood in the churn, which, from the time it 
left the artery, had no opportunity of parting with its ammonia, coagulated 
much more rapidly than that in an open vessel. The difference between the two 
was that the lower portion of the blood had been freely exposed to the influence 
of the foreign solid, whereas the other had only been subjected to the action 
of the wall of the tube. 

The same principle may be illustrated by an exceedingly simple experiment 
which I performed only this very day. Receiving blood from the throat of a 
bullock into two similar wide-mouthed bottles, I immediately stirred one of them 
with a clean ivory rod for ten seconds very gently, so as to avoid the intro- 


ON THE COAGULATION OF THE. BLOOD cL 


duction of any air, and then left both undisturbed. At the end of a certain 
number of minutes I found that, while the blood which had not been disturbed 
could be poured out as a fluid, with the exception of a thin layer of clot on 
the surface, and an incrustation on the interior of the vessel, the blood in the 
other vessel, which had been stirred for so brief a period, was already a solid 
mass. 

I have only lately been aware of the great influence exerted upon the blood 
by exposure for a very short time to a foreign solid, and I feel that many of my 
own experiments, and many performed by others, have been vitiated for want 
of this knowledge. Take, for example, the effect of a vacuum, which was 
observed by Sir Charles Scudamore to promote coagulation. This has been 
considered by Dr. Richardson as an illustration of his theory, the vacuum being 
supposed to act by favouring the escape of ammonia. I have lately inquired 
into this subject, and I feel no doubt whatever that the greater rapidity of 
coagulation in a vacuum depends simply on the greater disturbance of the fluid. 
I made the following experiment :—I filled three bottles, such as these, from 
the throat of a bullock, placed one of them under the small bell jar of an air- 
pump in good order and exhausted it, leaving the other two undisturbed. The 
blood happened to be slow in coagulating, and at the end of about forty minutes, 
in the vessels where the blood had been undisturbed, there was only a slight 
film of coagulum on the surface, whereas the blood under the vacuum was 
found on examination to have a very thick crust of clot upon it. But during 
the process of exhaustion the blood had bubbled very much. Indeed, any 
exhaustion of blood recently drawn which is sufficient to cause the evolution 
of its gases induces great bubbling, so that the pump cannot be used freely 
for fear of the froth overflowing. To this disturbance, involving the exposure 
of successive portions of blood in the bubbles to the sides of the vessel, I was 
inclined to attribute the more rapid coagulation; but in order to prove the 
point, I stirred for a few seconds the blood in one of the vessels hitherto undis- 
turbed. After eight minutes I emptied the three vessels. I found that that 
blood which had not been disturbed at all, either by the vacuum or by the rod, 
was still almost entirely fluid, only showing a thin crust upon the glass and 
on the surface exposed to the air. The blood which had been subjected to 
the vacuum had a thick crust of clot on the surface, and the sides of the glass 
were also thickly encrusted, but it still contained a considerable quantity of 
fluid that could be poured out from its interior. But that blood which had 
been stirred for only a few seconds was a solid mass throughout. In other 
words, gentle stirring of the blood for a few seconds had much greater effect in 
producing coagulation than the protracted and efficient exhaustion which was 


I2 


116 ON THE COAGULATION OF THE BLOOD 


continued for upwards of forty minutes, which was a considerable time after 
all evolution of gas, as indicated by bubbles, had ceased. 

Other experiments precisely similar in their effect were performed. I there- 
fore feel no hesitation in stating that the effects of a vacuum, regarding which, 
indeed, the statements of different experimenters have hitherto been conflicting, 
afford no evidence in favour of the ammonia theory. 

There is another point of very great interest in the history of the coagulation 
of the blood, which has been supposed to give support to the ammonia theory ; 
and that is, the effect of temperature. It has been long known that blood 
coagulates more rapidly at a high than at a low temperature, and, indeed, 
a little above the freezing-point remains entirely fluid. This seemed beautifully 
in harmony with the ammonia theory, as heat would naturally promote, and 
cold retard the evolution of the alkali, and a depression of temperature to near 
the freezing-point might be reasonably supposed to prevent its escape altogether. 
Indeed, Dr. Richardson mentions as a fact, that ammonia artificially mixed with 
blood ceases to be given off under such circumstances. 

Though thinking it not unlikely that this was the true explanation of the 
influence of temperature on coagulation, I thought it worth while to subject the 
matter to experiment. For that purpose I kept the blood of a horse fluid by 
means of a freezing mixture, and afterwards by ice-cold water; and when the 
corpuscles had subsided from the upper part of the blood, I cautiously added 
to the liquor sanguinis extremely dilute ice-cold acetic acid till it was of dis- 
tinctly acid reaction, the liquor sanguinis being of a colour that permitted the 
delicate application of test-paper, which is impossible with red blood. By this 
means any free ammonia which the fluid might have contained must have been 
neutralized, yet so long as it was kept in the cold it continued fluid, but when 
brought into a warm room coagulated just as a specimen which had not been 
acidulated. Thus, when there could be no free ammonia in the liquor sanguinis 
at all, it was still affected as usual by temperature. 

This experiment may not be satisfactory to all minds, though I confess 
it appears so to me; and, as this is a point of very great interest, I have sought 
in another way for evidence regarding it. First, however, I will mention an 
experiment which will not at once appear to bear on the question of temperature. 
I drew out a fine glass tube in such a way as to produce a fusiform receptacle 
continued longitudinally each way into a tube of almost capillary fineness for 
about two inches, which again expanded at the end, as represented in Fig. 3. 
Having squeezed out a drop of blood from my finger, I sucked up a portion 
into the tube till the receptacle A and its capillary extensions were filled. I then 
broke off the expanded ends, and placed the little tube thus filled, B, in a bath 


ON THE COAGULATION-OF THE BLOOD Lig 


of the strongest liquor ammoniae. Here certainly the blood was in circumstances 
in which it could not lose ammonia, but where any change in its amount must 
be by way of increase, and yet I found, on opening the receptacle by snapping 
it across after a scratch with a file, that instead of remaining longer fluid than 
in a watch-glass, the blood in it, being more in contact with the glass, was always 
more quickly coagulated, while coagulation was still more rapid in the capillary 
tube, where the blood was still more exposed to the influence of the foreign 
solid—the greater proximity to the liquor ammoniae having no influence 
upon it. 

It may perhaps be argued that the drop of blood employed being a small 
drop, and this small drop having been drawn up by suction into the tube, it 
might have parted with its ammonia before it got into the tube; but then 
(and now comes the bearing of the experiment on the effect of temperature) 
I found, if I placed a similar tube filled in the same way in a vessel of snow, 


A 
eee SEE SD 


mm 
B 


Fic. 3. 


so as not to freeze it but to keep it ice-cold, the blood in it remained fluid as 
long as I chose to keep it there. Now if all the ammonia had left the blood 
before it was introduced into the tube, cold ought, according to the ammonia 
theory, to have had no effect in retarding its coagulation ; for, according to 
that theory, cold operates by retaining the ammonia. On the other hand, if 
we take the other alternative and suppose that any ammonia which the blood 
might have contained was still in these tubes, the former experiment proves 
clearly that the retention of ammonia has-no effect in producing fluidity—no 
effect in preventing coagulation ; and if the retention of ammonia has no effect 
in preventing coagulation, then cold certainly cannot prevent coagulation by 
retaining the ammonia, because, even if retained, it would not influence the 
result. In whatever way we look at them, therefore, these simple experiments 
prove conclusively that cold maintains the fluidity of the blood in some manner 
unconnected with any influence it may exert upon ammonia. 

Then, again, I varied the experiment in this way. I placed such little 
tubes of blood in baths of liquor ammoniae at different temperatures. By 
careful management, guarding against the volatilization of ammonia and con- 
sequent reduction of temperature, I succeeded in employing satisfactorily a bath 
of liquor ammoniae at 100° Fahr., the blood being in the bath within a few seconds 


118 ON THE COAGULATION OF THE BLOOD 


of its leaving the vessels of my finger, and I found that the high temperature, 
though under such circumstances it could not possibly dissipate any ammonia 
from the blood, yet accelerated its coagulation in precisely the same way as 
when it was applied to blood in watch-glasses exposed to the air. 

It is clear, then, that the promotion of the solidification of fibrine by heat 
is as independent of the evolution of ammonia as the coagulation of albumen 
under the same agency. Indeed, it seems probable that the two cases are 
analogous, except that a higher temperature is required in the one than in 
the other. 

When fine tubes containing blood were placed in liquor ammoniae, the 
alkali acted only upon those parts which were close to the ends of the tubes ; 
a very small portion was rendered brown by it, and beyond that a little was 
kept permanently fluid, but the chief length of the blood in the tube was un- 
affected. Having thus ascertained that ammonia travels so slowly along tubes 
of this capillary fineness, I thought I might have an opportunity of giving the 
ammonia theory a fair test by tying such a tube as has been above described 
into the jugular vein of a rabbit and filling it directly from the vessel, and then ~ 
ascertaining whether there was any evidence of retardation of coagulation in 
the blood thus imprisoned. But I could discover no such evidence, although 
I sought for it in confirmation of a view I then held. To this, however, there 
is one special exception to be made, viz. in the case of asphyxia. I found that 
if two such tubes were filled from the same blood-vessel of a creature, one under 
normal circumstances, and the other after asphyxia had been induced, there 
was a most remarkable difference between the rates of coagulation of the blood 
in the two tubes, the asphyxial blood coagulating very much more slowly than 
the ordinary blood ; but when the asphyxial blood was shed into a watch-glass 
and air was blown through it, it coagulated rapidly, showing that in the state 
of asphyxia there must be some volatile element in the blood which has an 
effect in retarding coagulation. 

Supposing at first that this volatile element must be ammonia, I hoped 
to be able by chemical means to find evidence of its accumulation in asphyxia, 
and thus add a fact of great interest to physiology. Imitating experiments 
previously made by Dr. Richardson, I passed air successively through blood 
and through hydrochloric acid, and then estimated the amount of ammonia 
acquired by the latter by means of bichloride of platinum. In order to prevent 
the possibility of the loss of any ammonia, I directed blood from the carotid 
artery of a calf fairly into a Wolfe’s bottle by means of a vulcanized india- 
rubber tube tied into the vessel, and then drew a certain volume of air through 
it by means of an aspirating jar, the experiment being performed first before, 


ON THE COAGULATION OF THE BLOOD 119g 


and then during asphyxia. The same procedure was adopted with a second 
calf, the animal being in each case under chloroform, which does not interfere 
with the development during asphyxia of the peculiarity in the blood above 
alluded to, but I could not find satisfactory evidence of accumulation of am- 
monia ; and without going further into the question at present, I may say 
that it seems much more probable that the effect is due to carbonic acid, which 
is known to have a retarding influence on coagulation, and which probably 
accumulates greatly in asphyxial blood. 

But in justice to the author of the ammonia theory, and to myself, too, 
who at one time expressed a qualified belief in it, it is but fair to say that this 
theory is extremely plausible. It has been well shown by Dr. Richardson that 
ammonia is a substance well fitted to keep the blood fluid if it be present in 
a sufficient quantity. An experiment of my own illustrates very well the same 
point. I drew out a tube about a quarter of an inch in calibre (Fig. 4), so that 


Fic. 4 


while for two inches at one end it retained its original width, the rest (some 
ten inches) was pretty narrow, though far from having the capillary fineness 
of those before described. Into the thick part I introduced a drop of strong 
liquor ammoniae, A, and then securely corked that end of the tube, C. The 
object of this was that there should be a strong ammoniacal atmosphere in the 
narrow part of the tube. I then opened a branch of a vein, V, in the neck of 
a sheep, introduced the narrow end of the tube into the vessel, and pushing 
it in so that its orifice should be in the current of the main trunk of the vein, 
tied it in securely. I then removed the cork and made pressure on the vein 
at the cardiac side, causing the vessel to swell and blood to pass into the fine 
part of the tube, and before the blood had reached the part of the glass mois- 
tened by the ammonia I put in the cork again and withdrew the tube. In 
a short time, on introducing a hook of fine wire into the extremity of the tube, 
I found the blood already coagulated, but on filing off a small portion of the 
tube I found the blood there fluid. The portion of blood thus exposed soon 
coagulated, when, a second small piece of the tube being removed by the file, 
fluid blood was again disclosed, which again soon coagulated ; and this pro- 
ceeding was repeated with the same results time after time, till, near the thick 


120 ON THE COAGULATION OF THE BLOOD 


part of the tube, the ammonia in the blood was so strong as to prevent coagula- 
tion altogether. 

This experiment illustrates how fitted the ammonia is to maintain the 
fluidity of blood, and also how apt it is, when present in the blood, to fly speedily 
off from it, leaving it unimpaired in its coagulating properties ; and it must be 
confessed that the end of the tube sealed with a small clot resembled most 
deceptively the extremity of a divided artery similarly closed. But although 
the experiment seems in so far to favour the ammonia theory, it will tell differ- 
ently when I mention the object with which it was performed. 
It appeared to me that, if the cause of the fluidity of the blood 
was free ammonia, then, if I provided an ammoniacal atmo- 
sphere in the tube, and introduced blood by pressure directly 
from the vein into this ammoniacal atmosphere, this blood, 
lying between the strong ammoniacal atmosphere on the 
one side and the ammonia naturally present in the blood 
within the vein on the other side, ought to remain fluid ; and 
if it did remain fluid, this would tend to confirm the ammonia 
theory by making it appear that the volatile material was the 
same at both ends of the tube. But, to my disappointment, I 
invariably found that if I drew away the tube after a few 
minutes only had elapsed, there was already a clot in its ex- 
tremity ; in other words, the ammonia had diffused from the 
end of the tube into the blood within the vein as into a non- 
ammoniacal atmosphere. This experiment alone, if duly 
considered, would, I think, suffice to show that the blood does 
not contain enough ammonia to account for its fluidity. 

One more experiment, however, may be adduced with 

5 the same object. I mounted a short but wide glass tube, open 
at both ends (T, Fig. 5), upon the end of a piece of strong wire, W, and con- 
nected with the latter a coil of fine silver wire, S, so that it hung freely in 
the tube. I then opened the carotid artery of a horse, and through the wound 
instantly thrust in the apparatus so far that I was sure the tube lay in the 
common carotid, which in veterinary language means the enormous trunk 
common to both sides of the neck of the animal. The tube being open at both 
ends, and slightly funnel-shaped at that end which was directed towards the 
heart, had thus a full current of arterial blood streaming through it. Having 
ascertained how long the arterial blood took to show the first appearance of 
coagulation in a watch-glass, I very soon after removed the apparatus, and, on 
taking out the coil of silver wire, found that it was already crusted over with 


Fic. 5; 


ON EEE COAGULATION, OF THE BLOOD 120 


coagulum. Yet here assuredly there had been no opportunity for the escape 
of ammonia. 

From this experiment it is obvious that there is a very great difference 
between ordinary solid matter and the living vessels in their relation to the 
blood. But the same conclusion may be drawn much more simply from experi- 
ments which I had the opportunity of performing after making an observation 
which it seems strange should have been left for me to make, and which, I may 
say, was made by myself purely accidentally ; and this is, that the blood of 
mammalia, although it coagulates soon after death in the heart and the principal 
arterial and venous trunks, remains fluid for an indefinite period in the small 
vessels. If, therefore, a ligature be tied round the foot of a living sheep a little 
below the joint which is divided by the butcher, the foot being removed and 
taken home with the blood retained in the veins by the ligature, we have a ready 
opportunity of investigating the subject of coagulation, and of making observa- 
tions as satisfactory as they are simple. Here are two feet provided in the way 
I have alluded to. A superficial vein in each foot has been exposed. The 
veins I see have contracted very much since I reflected the skin from them 
before our meeting ; and I may remark that such contraction, dependent on 
muscular action, may occur days after amputation, indicating the persistence 
of vital properties in the veins. Now as I cut across this vein, blood flows out, 
fluid but coagulable. Into the vein of this other foot has been introduced 
a piece of fine silver wire, and when I slit up the vein you will see the effect 
it has produced. Exactly as far as the silver wire extends, so far is there a clot 
in this vessel. Now this experiment, very simple as it is, is of itself sufficient 
to prove the vital theory in the sense that the living vessels differ entirely from 
ordinary solids in their relation to the blood. It is perfectly clear that by 
introducing a clean piece of silver wire (and platinum or glass or any other 
substance chemically inert would have had the same effect) I do not add any 
chemical material or facilitate the escape of any, and yet coagulation occurs 
round about the foreign solid. 

Again, if a blood-vessel be injured at any part, coagulation will occur at 
the seat of injury. As a good illustration of this, and also as bearing upon the 
ammonia theory, I may mention the following experiment. Having squeezed 
the blood out of a limited portion of one of the veins of a sheep’s foot, and pre- 
vented its return by appropriate means, I treated the empty portion with caustic 
ammonia, the neighbouring parts of the vein being protected from the tritating 
vapour by lint steeped in olive oil. After the smell of ammonia had passed off, 
I let the blood flow back again and left it undisturbed for a while, when I found 
on examination a cylindrical clot in the part that had been treated with ammonia, 


122 ON THE COAGULATION OF THE BLOOD 


while in the adjacent parts of the same vessel the blood remained fluid. I re- 
peated this experiment several times and always with the same result. Where 
the ammonia had acted there was a clot. The chemical agent used here was 
one which, so long as any of it remained, would keep the blood fluid, yet its 
ultimate effect was to induce coagulation, the vital properties of the vein having 
been destroyed by it. 

If a needle or a piece of silver wire is introduced for a short time into one 
of the veins of the sheep’s foot, it is found on withdrawal to be covered over 
with a very thin crust of fibrine, whereas the wall of the vessel itself is never 
found to have fibrine or coagulum adhering to it unless it has been injured. Now 
this seems to imply that the ordinary solid is the active agent with reference 
to coagulation—that it is not that the blood is maintained fluid by any action 
of the living vessels, but that it is induced to coagulate by an attractive agency 
on the part of the foreign solid. We see at any rate that the foreign solid has 
an attraction for fibrine which the wall of the vessel has not. 

And yet I own I was at first inclined to think that the blood-vessels must 
in some way actively prevent coagulation. There were two considerations that 
led to this view. One was, that the blood remained fluid in the small vessels 
after death, but coagulated in the large. Now why should that be? It seemed 
only susceptible of explanation from there being some connexion between the 
size of the vessel and the circumstance of coagulation. It looked as if in the 
small veins the action of the wall of the vessel was able to control the blood 
and keep it fluid, but that the large mass in the principal trunks could not be 
so kept under control. The other circumstance was the rapid coagulation of 
a large quantity of blood shed into a basin. Why should this occur unless 
there was some spontaneous tendency in the blood to coagulate? It seemed 
scarcely credible that it was the result of contact with the surface of the basin. 

Both these notions, however, have since been swept away. In the first 
place, I have observed recently that it is by no means only in small vessels 
that the blood remains fluid after death. If blood be retained within the 
jugular vein of a horse or ox by the application of ligatures, either before or 
after the animal has been struck with the pole-axe, it will often continue fluid, 
but coagulable, in that vessel, which is upwards of an inch in diameter, for 
twenty-four or even forty-eight hours after it has been removed from the body. 
I say often, but not always. The jugular vein seems to be in that intermediate 
condition, between the heart and the small vessels, in which it is uncertain 
whether it will retain its vital properties for many hours, or will lose them in 
the course of one hour or so. Unfortunately for my present purpose, it happens 
that in this jugular vein, removed from an ox six hours ago, coagulation has 


ON, THE, COAGULATION OF THE BLOOD 23 


already commenced, as I can ascertain by squeezing the vessels between my 
fingers. But now that I lay open the vessel, you observe that the chief mass 
of its contained blood is still fluid, and we shall at all events have an opportunity 
of seeing that what is now fluid will in a short time be coagulated. It is an 
interesting circumstance with reference to the question which we are now con- 
sidering, that the coagulation always begins in contact with the vein, indicating 
that it is not the wall of the vessel that keeps the blood fluid, but that, on the 
contrary, the wall of the vessel, when deprived of vital properties, makes the 
blood coagulate. 

The observation of the persistent fluidity of the blood in these large vessels 
furnished the opportunity of making a very satisfactory experiment, which I 
hoped to have exhibited before the Society, but as there was some clot in the vein 
I did not think fit to run the risk of failure. The experiment is performed in the 
following way. A piece of steel wire is wound spirally round one of the veins 
in its turgid condition, and with a needle and thread the coats of the vessel 
are stitched here and there to the wire, care being taken to avoid puncturing 
the lining membrane, and thus the vessel is converted into a rigid cup. Two 
such cups being prepared, and the lining membrane of the vein being everted 
at the orifice of each so as to avoid contact of the blood with any injured tissue, 
I found that, after pouring blood to and fro through the air in a small stream 
from one venous receptacle into the other half a dozen times, and closing the 
orifice of the receptacle to prevent drying, the blood was still more or less com- 
pletely fluid after the lapse of eight or ten hours. On the other hand, if a fine 
sewing needle is pushed through the wall of an unopened vessel so that its end 
may lie in the blood, it is found on examination, after a certain time has elapsed 
that the needle is surrounded with an encrusting clot. It is scarcely necessary 
to point out how entirely the ammonia theory and the oxygen theory, as well 
as that of rest, fail to account for facts like these. 

While the blood may remain fluid for forty-eight hours in the jugular vein oi 
a horse or an ox, it coagulates soon after death in the heart of very small animals, 
such as mice, so that it 1s obvious that the continuance of fluidity in small 
vessels is not due to their small size. 

It is a very curious question, What is the cause of the blood remaining 
so much longer fluid in some vessels than in others? I believe that we must 
accept it simply as an ultimate fact, that just as the brain loses its vital pro- 
perties earlier than the ganglia of the heart, so the heart and principal vascular 
trunks lose theirs sooner than the smaller vessels of the viscera, or than more 
superficial vessels, be they large or small. We can see a final cause for this, 
so to speak. So long as the heart is acting, circulation will be sure to go on 


124 ON THE COAGULATION OF THE BLOOD 


in the heart and principal trunks; whereas, on the contrary, the more super- 
ficial parts are liable to temporary causes of stagnation, and occasionally to 
what amounts to practical severance from vascular and nervous connexion 
with the rest of the body ; and it is, so to speak, of great importance that the 
blood should not coagulate so speedily in the vessels of a limb thus circum- 
stanced as it does in the heart after it has ceased to beat. Were it not for this 
provision, the surgeon would be unable to apply a tourniquet without fear of 
coagulation occurring in the vessels of the limb. As an illustration of the im- 
portance of a knowledge of these facts, I may mention a case that once occurred 
in my own practice. I was asked by a surgeon in a country district to amputate 
an arm which he despaired of. The brachial artery had been wounded, as well 
as veins and nerves, and at last, being foiled with the haemorrhage, he wound 
a long bandage round the limb at the seat of the wound as tightly as he possibly 
could. It had been in this condition with the bandage thus applied for forty- 
eight hours when I reached the patient, and the limb had all the appearance 
of being dead. It was perfectly cold, and any colour which it had was of a livid 
tint. But having been lately engaged in some of the experiments which I have 
been describing, and having thus become much impressed with the persistent 
vitality of the tissues and the concomitant fluidity of the blood, I determined 
to give the limb a chance by tying the brachial artery. Before I left the patient’s 
house he had already a pulse at the wrist, and I afterwards had the satisfaction 
of hearing that the arm had proved a useful one. 

One of the two arguments in favour of activity on the part of the vessels asa 
cause of the fluidity of the blood having been completely disposed of, let us now 
consider the other, viz. the rapid coagulation of blood shed into a basin, appearing 
at first sight to imply a spontaneous tendency of the blood to coagulate, such as 
would have to be counteracted by the vessels. This also has proved fallacious. 

In the first place it appears that the coagulation, after all, does not go on 
in a basin so suddenly as one would at first sight suppose, but always com- 
mences in contact with the foreign solid. When blood has been shed into 
a glass jar, if, on the first appearance of a film at the surface, you introduce 
a mounted needle curved at the end between the blood and the side of the glass 
and make a slight rotatory movement of the handle, you see through the glass 
the point of the needle detaching a layer of clot whatever part you may examine. 
The process of coagulation having thus commenced in contact with the surface 
of the vessel into which the blood is shed, may, under favourable circumstances, 
be ascertained to travel inwards, like advancing crystallization, towards the 
centre of the mass. It appears, however, that this extension of the coagulating 


* See above, p. 85. 


ON UTE COAGULATION OF THE BLOOD 125 


process would not take place had not the blood been prepared for the change 
by contact, during the process of shedding, with the injured orifice of the blood- 
vessel and with the surface of the receptacle. I have only very recently become 
acquainted with the remarkable subtlety of the influence exerted upon blood 
by ordinary solids. I was long since struck with the fact that if I introduced 
the point of an ordinary sewing needle through the wall of a vein in a sheep’s 
foot and left it for twelve hours undisturbed, the clot was still confined to a 
crust round the point of the needle, implying that coagulum has only a very 
limited power of extension. I thought, therefore, that by proper management 
it might be possible to keep blood fluid in a vessel of ordinary solid matter 
lined with clot. But various attempts made with this object failed entirely, 
till I lately adopted the following expedient. Having opened the distal end 
of an ox’s jugular vein containing blood and held in the vertical position, taking 
care to avoid contact of any of the blood with the wounded edge of the vessel, 
I slipped steadily down into it a cylindrical tube of thin glass, somewhat smaller 
in diameter than the vein, open at both ends, and with the lower edge ground 
smooth in order that it might pass readily over the lining membrane, and so 
disturb the blood as little as possible by its introduction, and influence only 
the circumferential parts of its contents. The tube was then kept pressed 
down vertically upon the bottom of the vein by a weight, in a room as free as 
possible from vibration, and I found on examining it at the end of twelve hours 
that the clot was a tubular one, consisting of a crust about one-eighth of an inch 
thick next the glass and the part exposed to the air, but containing in its interior 
fluid and rapidly coagulable blood. In another such experiment, continued for 
twenty-four hours, though the crust of clot was thicker, the central part still 
furnished coagulable blood. 

But it may perhaps be argued by those who say that the blood-vessels are 
active in maintaining fluidity that the small portion of the vein covering the 
end of the tube was acting upon the blood, which certainly was fluid where in 
contact with it, the clot being in the form of a tube open at the lower end. To 
guard against such an objection I made the following experiment :—I extended 
a tube like that above described by means of thin sheet gutta-percha, G (Fig. 6 a), 
contriving that the internal surface of the gutta-percha should be pertectly 
continuous with that of the glass tube as represented in section in Fig. 6 0. 
The lower part of the gutta-percha tissue was strengthened by a ring of soft 
flexible wire such as is used by veterinary surgeons for sutures, and the wire, W, 
was also extended upwards to the top of the glass so as to maintain the rigidity of 
the gutta-percha portion during its introduction into a vein, but at the same time, 
from its softness, permit the gutta-percha part to be bent at a right angle after 


126 ON THE COAGULATION OF THE BLOOD 


it had been introduced, and so close the orifice of the glass tube with ordinary 
solid matter. In Fig. 6 c the tube is represented pressed down by a weight 
in a vein, V, with blood, B, in the glass portion, while the gutta-percha part closes 
it below. At the same time I performed a comparative experiment, to which 
I would invite particular attention, although I am sorry at this late hour to 
occupy the attention of the Society so long. I tied a thin piece of gutta-percha 
tissue over the lower end of a similar glass tube, and simply poured blood into 
it from the jugular vein of an ox. I wished to compare the condition of blood 
which had been simply poured into a tube, with blood which had been intro- 
duced without any disturbance of its central parts. But in order to make the 


& 
Se 
° 


YY 


es 


ij 


Lihat ia 


< 


WU 


\ 
‘hy, 


Fic. 6. 


experiment a fair one, as it might be said that the blood poured from the vein 
had been more exposed to the air than that into which the tube was slipped, 
I proceeded in the following way: I obtained a long vein containing plenty 
of blood, and having first filled the second tube, with the gutta-percha bottom 
(Fig. 6d), by simply pouring blood into it from the vein, I cut off a portion of 
the vein which had been thus emptied, and having tied one end and everted 
the lining membrane of the other end, and having also everted the lining mem- 
brane of the orifice of the remainder of the vessel which was full, I poured the 
blood from the full portion through the air into the empty part. In doing this 
I had difficulty in getting blood enough, and it passed through the air in slow 
drops, and that only when the vein was squeezed by my warm hand. At last, 
having introduced sufficient for the purpose, I slipped down the compound 
tube and bent its gutta-percha portion, as represented in Fig. 6c, and left both 
tubes for a while undisturbed. At the end of three hours and a half I found 
that the blood which had been simply poured in was a mass of clot, and fluid 


ON THE COAGULATION OF THE BLOOD £27 


squeezed from it yielded no threads of fibrine, coagulation being complete. How 
long it had been so I do not know. I did not examine the other blood until 
seven hours and three quarters had expired, and then found that, just as in 
the cases where a simple glass tube was introduced, the clot was tubular, and 
the chief part of the blood was still fluid in its interior, the only difference being 
that in this case the clot formed a complete capsule, being continued over the 
gutta-percha instead of being deficient below, as it was when the vein closed 
the end of the tube. Now if we consider the two parts of this comparative 
experiment, we see that the receptacles in which the blood was ultimately con- 
tained were precisely similar in the two cases, viz. glass tubes closed below 
with gutta-percha ; and that the blood which was simply poured into the tube 
was much less exposed to the air than the other, and also was not subjected, 
like it, to elevation of temperature, a circumstance which promotes coagulation ; 
but yet this blood became completely coagulated in a comparatively short time, 
whereas the other after a much longer time was coagulated only in a layer in 
contact with the foreign solid. But in the latter case the blood had been so 
introduced as to avoid direct action of ordinary matter on any but the circum- 
ferential parts of it, whereas in the former, though poured quickly, it had run 
down the side of the glass, and as a consequence of this almost momentary 
contact with the foreign solid, the central parts, like the circumferential, under- 
went the process of coagulation. 

Mysterious as this subtle agency of ordinary solids must appear, its occur- 
rence is thus matter of experimental demonstration, and by it the coagulation 
of blood shed into a basin is accounted for ; while it is also shown conclusively 
from this experiment that the blood, as it exists within the vessels, has no spon- 
taneous tendency to coagulate, and therefore that the notion of any action 
on the part of the blood-vessels to prevent coagulation is entirely out of the 
question. The peculiarity of the living vessels consists not in any such action 
upon the blood, but in the circumstance, remarkable indeed as it is, that their 
lining membrane, when in a state of health, is entirely negative in its relation 
to coagulation, and fails to cause that molecular disturbance or, if we may so 
speak, catalytic action which is produced upon the blood by all ordinary matter. 

I afterwards found that the simplest method of maintaining blood fluid 
in a vessel composed entirely of ordinary matter was to employ a glass tube 
similar to those above described, except that its upper end was closed by a cork 
perforated by a narrow tube terminating in a piece of vulcanized india-rubber 
tubing that could be closed by a clamp. This tube was slipped down into a vein 
till the blood, having filled it completely, showed itself at the orifice of the india- 
rubber tubing, to which the clamp was then applied. The whole apparatus 


128 ON THE COAGULATION OF THE BLOOD 


was now quickly inverted, and the vein was drawn off from over the mouth of 
the tube, which was then covered with gutta-percha tissue to prevent evapora- 
tion. After the inverted tube had been kept undisturbed in the vertical position 
for nineteen hours and three-quarters coagulable blood was obtained from the 
interior of the clot. 

We have seen that a clot has but very slight tendency to induce coagulation 
in its vicinity unless the blood has been acted on by an ordinary solid, and 
it is probable that with perfectly healthy blood it would be unable to produce 
such an effect at all. This appears to me to be very interesting physiologically, 
but especially so with reference to pathology. I must not go now fully into 
the circumstances that lead me to it, but I may express the opinion I have 
formed, that clot must be regarded as living tissue in its relation to the blood. 
It is no doubt a very peculiar form of tissue, in this respect—that it is soft, easily 
lacerable, and easily impaired in its vital properties. If disturbed, as in an 
aneurysm, it will readily be brought into that condition which leads to the 
deposition of more clot ; but if undisturbed, it not only fails to induce further 
coagulation, but seems to undergo spontaneous organization. I have seen 
a clot in the right side of the heart, and extending into the pulmonary artery 
and its branches, unconnected with the lining membrane of auricle or ventricle 
or with the pulmonary artery except at one small spot where it had a slight 
adhesion, developed into perfect fibrous tissue by virtue, it would appear, of its 
own inherent properties. Another observation which I once made, and which 
then completely puzzled me, now seems capable of explanation. In laying open 
the blood-vessels of a dead body I observed in many of the veins a delicate 
white lace-like tissue which evidently must have been formed from a clot. This 
I now believe to have had the same relation to the coagulum as the flimsy cellular 
tissue of old adhesions has to lymph. 

It may not be altogether superfluous to mention some other facts illustrative 
of the active influence of ordinary matter in promoting coagulation, and the 
negative character of the lining membrane of the vessels. I find that a needle 
introduced into one of the veins of the foot of a sheep for a much shorter time 
than is necessary to produce the first appearance of the actual deposit of fibrine 
upon it, leads after a while to coagulation where the needle had lain; in other 
words, that a foreign solid, by a short period of action on the blood, brings 
about a change that results in coagulation, though the blood still lies in the 
living vessels. I have also ascertained that after blood has been made to coagu- 
late in a particular vessel by introducing a needle into it, if the coagulum as 
well as needle is removed, and more fluid blood is allowed to pass in, this blood 
remains fluid for an indefinite period, showing that the needle had not impaired 


ON THE COAGULATION OF THE BLOOD 129 


the properties of the vessel by its presence; so that the previous coagulation 
must be attributed not to any loss of power in the vein but simply to the action 
of the foreign solid. 

In seeking for an analogy to this remarkable effect of ordinary solids upon 
the blood, we are naturally led to the beautiful observations of Professor Graham, 
lately published in the Philosophical Transactions. He has there shown what 
insignificant causes are often sufficient to induce a change from the fluid or 
soluble to the ‘ pectous’ or insoluble condition of ‘ colloidal’ forms of matter. 
Indeed, Mr. Graham has himself alluded to the coagulation of fibrine as being 
probably an example of such a transition. 

There is, however, another remarkable circumstance that must be taken 
into consideration, of which I myself have been only recently aware, and which 
may be new to several Fellows of the Society ; and that is, that in spite of the 
influence of an ordinary solid the liquor sanguinis is not capable of coagulating 
per se. It was observed many years ago by my colleague, Professor Andrew 
Buchanan, of Glasgow, that the fluid of a hydrocele, generally regarded as mere 
serum, coagulated firmly if a little coagulum of blood diffused in water was 
added to it—an effect which he was disposed to attribute to the agency of the 
white corpuscles. I repeated Dr. Andrew Buchanan’s observations last year, 
and satisfied myself first that the diffused clot did not act simply by providing 
solid particles to serve as starting-points for the coagulating process. I tried 
various different materials in a finely divided state, and found that none of 
them, except blood, produced the slightest effect. But I found that if a mixture 
of serum and red corpuscles from a clot was added to some of this hydrocele- 
fluid, it was soon converted into a firm solid mass. If a small quantity of the 
serum and corpuscles was dropped into the fluid and allowed to subside without 
stirring, coagulation rapidly took place in those parts where the red corpuscles 
lay, while other parts of the fluid remained for a long time uncoagulated. This 
seemed to indicate that the red corpuscles had a special virtue in inducing the 
change. I confess, however, that till very lately I was inclined to suppose 
that in the hydrocele-fluid the fibrine must be in some peculiar spurious form. 
We know that the buffy coat of the horse’s blood coagulates in a glass without 
addition of clot, and we know that lymph coagulates, so that I did not doubt 
that liquor sanguinis would always undergo the change when influenced by 
ordinary matter. But an observation which I made not many days ago shows 
that this was a mistake. I obtained the jugular vein of a horse, and having 
kept it for a while in a vertical position till I could see through its transparent 
coats that the red corpuscles had fallen from the upper part, I removed all 

* Proceedings of the Glasgow Philosophical Society, February 19, 1845. 


LISTER I Kk 


130 ON THE COAGULATION OF THE BLOOD 


bloody tissue from that part of the vein, and punctured it so as to let out the 
liquor sanguinis into a glass. Finding after eighteen minutes that the liquid 
had not begun to coagulate, I added a drop of serum and corpuscles to a portion 
of it, and within seven minutes there was a clot wherever the corpuscles lay, 
whereas the rest of the fluid was still very imperfectly coagulated after another 
half-hour had elapsed. That the liquor sanguinis to which no addition had 
been made coagulated at all was sufficiently explained by microscopic investiga- 
tion, which showed not only abundant white corpuscles, but also several isolated 
red ones that had not subsided. This observation was made three hours after 
the death of the horse, but I obtained essentially similar results on repeating 
the experiment in another horse an hour after death; so that there can be 
no doubt whatever that the fibrine was in the same condition as it is in the 
blood-vessels of a living animal. The observation appears also particularly 
satisfactory on this account, that the liquor sanguinis was not separated from the 
corpuscles by any process of transudation through the walls of the blood-vessels, 
which might be conceived to involve retention of some constituent of the lquid, 
which, though in solution, might be unable to pass through their pores, but 
simply by the subsidence of the corpuscles, which must have left all the materials 
of the hquor sanguinis behind them. Hence it is proved beyond question that 
if the hquor sanguinis could be separated completely from the blood-corpuscles 
it would resemble the fluid of hydrocele in being incapable of coagulation when 
shed into a cup. 

Now this struck me as a very satisfactory and beautiful truth, inasmuch 
as it clears away all the old mystery of the distinction between inflammatory 
exudations and dropsical effusions. Dropsical effusions, exhibiting little dis- 
position to coagulate, have been supposed to consist almost exclusively of 
serum, and the exudation of the entire liquor sanguinis has been regarded as 
the special characteristic of inflammation; and very unsatisfactory theories 
have been put forward by ingenious pathologists to account for this difference. 
But it now appears that a dropsical effusion, like that of hydrocele, is undis- 
tinguishable from pure liquor sanguinis. 

Various dropsical effusions have been lately investigated with reference to 
their coagulability on the addition of blood-corpuscles by Dr. Schmidt of 
Dorpat, who finds that while they differ from one another in the amount of 
water they contain (just as is the case with serum filtered artificially through 
animal membranes under different degrees of pressure), yet they are all but 
universally coagulable. Schmidt has also carried the investigation further. 
He has found that by chemical means he can extract from the red corpuscles 
a soluble material which, when added to these exudations, leads to coagulation. 


ON THE COAGULATION OF THE BLOOD 131 


In other words, he shows that the corpuscles do not act as living cells, but by 
virtue of a chemical material which they contain, which can be used in the state 
of solution, free from any solid particles whatever. He found also that the 
aqueous humour made a dropsical effusion coagulate, and that the same effect was 
produced by a material extracted from the non-vascular part of the cornea. 
Hence he regards the blood-corpuscles as only resembling other forms of tissue 
in possessing this property. These observations are extremely interesting, if 
trustworthy ; and that they are so I do not at all doubt, but having only read 
Schmidt’s papers within the last day or two I have not yet had opportunity of 
verifying his statements.’ 

It remains to be ascertained what share the material derived from the 
corpuscles has in the composition of the fibrine. Schmidt inclines to the opinion 
that the fibrine is probably composed, in about equal proportions, of a substance 
furnished by them and one present in the liquor sanguinis. If this be true, the 
action of an ordinary solid in determining the union of the components of the 
fibrine may be compared to the operation of spongy platinum in promoting the 
combination of oxygen and hydrogen. 

It may be asked, How comes it that when the blood of a horse is shed into 
a cup, the buffy layer coagulates as rapidly, or nearly so, as the lower parts rich 
in corpuscles ? 

This is indeed a question well worthy of careful study. We know that 
the liquor sanguinis left by the subsidence of the red corpuscles within a healthy 
vein is incapable of coagulating when shed, except in a slow manner, which is 
accounted for by the corpuscles that remain behind in it. Hence it appears 
that when the blood as a whole is shed into a glass, the agency of the ordinary 
solid leads the corpuscles to communicate to the liquor sanguinis, before they 
subside, a material or at least an influence which confers upon it a disposition 
to coagulate, though it still remains fluid for some time after they have left it. 
Just as we have seen that a very short time of action of the ordinary solid upon 
the blood as a whole is sufficient to give rise to coagulation, so we now see that, 
provided an ordinary solid be in operation, the presence of the corpuscles for 
but a little while is enough to make the liquor sanguinis spontaneously 
coagulable, though not immediately solidified. We shall see, before concluding, 
an illustration of the importance of this fact to pathology. 


* Since this lecture was delivered I have verified an important observation made by Schmidt, viz. 
that a given amount of corpuscles causes complete coagulation of only a limited quantity of hydrocele- 
fluid. From this he draws the inference that the action of the corpuscles cannot be of the nature of 
fermentation—the coagulative efficacy of the corpuscles being not continued indefinitely, but becoming 
exhausted in the process of coagulation. For Schmidt’s papers, see Archiv fiir Anat. Phys., &c., 1861 
and 1862. 

K 2 


132 ON THE COAGULATION OF THE BLOOD 


It remains to be added that serous membranes resemble the hning mem- 
brane of the blood-vessels in their relations to the blood, as is implied by John 
Hunter’s observation that blood which had lain for several days in a hydrocele 
coagulated when let out. The same thing is well illustrated in a frog prepared 
like this which I now exhibit. About four hours ago, a knife having been passed 
between the brain and cord to deprive the creature of voluntary motion in the 
limbs and trunk, the peritoneal cavity was laid open in the middle line, and its 
edges being kept raised and drawn aside by pins, I seized the apex of the ven- 
tricle of the heart with forceps and removed it with scissors. In a short time 
the whole of the animal’s blood was in the peritoneum, and it may be seen that 
it is still fluid in spite of this long-continued exposure. When I first performed 
the experiment three years and a half ago, the weather being cool (about 45° 
Fahr.) and a piece of damp lint being kept suspended above the frog to prevent 
evaporation and access of dust, I found that the blood remained fluid in the 
peritoneal cavity for four days, except a thin film on the surface and a crust of 
clot on the wounded part of the heart ; but apiece of clean glass placed in the 
blood in the peritoneum became speedily coated with coagulum. Here, it will 
be observed, not merely the liquor sanguinis, but the corpuscles also were present 
in the serous cavity, yet no coagulation took place in contact with its walls. 

I think it probable, though not yet proved, that all living tissues have 
these properties with reference to the blood. We know that the interstices 
of the cellular tissue contain coagulable fluid, and I have seen anasarcous liquid 
coagulate after emission, but this indeed may possibly have been merely liquor 
sanguinis coagulating in consequence of slight admixture of blood-corpuscles 
from the wounds made in obtaining it. 

Looking now at the principal results which we have arrived at, it must, 
in the first place, be admitted that the ammonia theory is to be discarded as 
entirely fallacious. The fact that this theory is exceedingly plausible, and has 
been supported by many ingenious arguments and experiments, is of course 
no reason why we should retain it if unsound. On the contrary, the more 
specious it is the more necessary is it that it should be effectually cleared away, 
for it mystifies the subject of coagulation most seriously ; and I may say, for 
my own part, that it has cost me an amount of experimental labour of which 
the illustrations brought forward this evening convey but little idea. Still 
these have been, I trust, sufficient to show that the coagulation of the blood is 
in no degree connected with the evolution of ammonia, any more than with 
the influence of oxygen or of rest. The real cause of the coagulation of the 
blood, when shed from the body, is the influence exerted upon it by ordinary 
matter, the contact of which for a very brief period effects a change in the blood, 


ON THE COAGULATION OF THE BLOOD 133 


inducing a mutual reaction between its solid and fluid constituents, in which 
the corpuscles impart to the liquor sanguinis a disposition to coagulate. This 
reaction is probably simply chemical in its nature, yet its product, the fibrine, 
when mixed with blood-corpuscles in the form of an undisturbed coagulum, 
resembles healthy living tissues in being incapable of that catalytic action 
upon the blood which is effected by all ordinary solids, and also by the tissues 
themselves when deprived of their vital properties. 

These principles have, of course, very extensive applications to the study 
of disease, but I must content myself with alluding very briefly to inflammation, 
the most important of all pathological conditions. 

If we inquire what is the great peculiarity of inflamed parts in relation 
to the blood as examined by the naked eye, we see that it consists in a tendency 
to induce coagulation in their vicinity—implying, according to the conclusions 
just stated, that the affected tissues have lost for the time being their vital 
properties, and comport themselves like ordinary solids. Thus, when an artery 
or vein is inflamed, coagulation occurs upon its interior, in spite of the current 
of blood, precisely as would take place if it had been artificially deprived of its 
vital properties. On one occasion I simulated the characteristic adherent clot 
of phlebitis by treating the jugular vein of a living sheep with caustic ammonia, 
and then allowing the circulation to go on through the vessel for a while, when, 
on slitting it up, I found its lining membrane studded with grains of pink fibrine 
which could be detached only by scraping firmly with the edge of a knife. Again, 
comparing an inflammatory exudation into the pericardium or into the inter- 
stices of the cellular tissue with dropsical effusions into the same situations, we 
are struck with the fact that, while the liquor sanguinis effused in dropsy remains 
fluid, the inflammatory product coagulates. Now we know that in intense 
inflammation the capillaries are choked more or less with accumulated blood- 
corpuscles, which must cause great increase in the pressure of the blood upon 
their walls; and from what we know of the effect of venous obstruction in 
causing dropsical effusion of liquor sanguinis through increased pressure, we are 
sure that we have in the inflammatory state the physical conditions for a similar 
transudation of fluid through the walls of the capillaries. And the natural 
interpretation of the difference in the two cases as regards coagulation seems 
to be, that whereas in dropsy the fluid is forced through the pores of healthy 
vessels, in inflammation the capillary parietes have lost their healthy condition, 
and act like ordinary matter; so that the liquor sanguinis, having been sub- 
jected, immediately before effusion, to the combined influence of the injured 
tissue and the blood-corpuscles, has acquired a disposition to coagulate, just 
like the buffy coat of horses’ blood shed into a glass, or like the frog’s liquor 


134 ON THE COAGULATION OF THE BLOOD 


sanguinis filtered by Miiller from its corpuscles, the injured vessels acting upon 
the blood like the filter. 

This view of the condition of intensely inflamed parts is exactly that to 
which I was led some years ago by a microscopic investigation, the results of 
which were detailed in a paper that received the honour of a place in the 
Philosophical Transactions... It was there shown, as I think I may venture to 
say, that the tissues generally are capable of being reduced under the action 
of irritants to a state quite distinct from death, but in which they are never- 
theless temporarily deprived of all vital power, and that inflammatory con- 
gestion is due to the blood-corpuscles acquiring adhesiveness such as they have 
outside the body, in consequence of the irritated tissues acting towards them 
like ordinary solids. 

I cannot avoid expressing my satisfaction that this inquiry into the coagu- 
lation of the blood has furnished independent confirmation of my previous 
conclusions regarding the nature of inflammation. 


* «On the Early Stages of Inflammation,’ Phi/. Tvans., 1858 (p. 209 of this volume). 


ON ANAESTHETICS 


[Holmes’s System of Surgery, vol. ii, third edition. London, 1883.] 


PART I. WRITTEN 1861 


To prevent or diminish pain in surgical operations is an object so desirable, 
that many in various ages in the history of Medicine have sought to attain it, 
either by means of narcotic drugs designed to act on the body generally, or by 
compressing or otherwise locally affecting the nerves of the part concerned. 

The first really valuable suggestion, however, was made in the year 1800 
by Sir Humphrey Davy, who, having himself experienced relief from pain when 
breathing nitrous oxide gas, threw out the hint that it might probably be em- 
ployed with advantage to produce a similar effect in surgical practice. 

The same idea occurred, after the lapse of nearly half a century, to Dr. 
Horace Wells, a dentist in Hartford, Connecticut, who, in 1844, underwent the 
extraction of a tooth without pain after inhaling the gas, and gave it with satis- 
factory results to several of his patients ; but he soon after found the practice 
so uncertain that he abandoned it entirely.® 

About the same period Dr. W. T. G. Morton, of Boston, in America, who 
had previously been a partner with Wells, but did not, as he informs us, receive 
any suggestion from him, became possessed with the desire of discovering an 
efficient anaesthetic, and commenced a series of experiments upon himself and 
the lower animals, which at last resulted in his extracting a tooth painlessly 
from a patient to whom he had administered the vapour of sulphuric ether by 
inhalation. This was on September 30, 1846.4 Soon afterwards he publicly 
exhibited his method at the Massachusetts General Hospital; and thence- 
forward anaesthesia in surgery was an established blessing to mankind. 

Sulphuric ether is still extensively used as an anaesthetic in America, 
but in Europe chloroform is generally preferred to it. Disguised under the 
name ‘ chloric ether’, in which it exists diluted with spirit of wine, this agent 
was the subject of Dr. Morton’s first experiment upon himself ;° and it was 


 ] 
1 For much curious information regarding the history of this subject the reader is referred to the 
work of the late Dr. Snow on Anaesthetics. 
* Chemical Researches, p. 556. 
® Statements of William T.G. Morton, M.D., on his Claim to the Discovery of the Anaesthetic Pro- 
perties of Ether, &c. Washington, 1853, pp. 42 et seq. 
* Dr. Morton’s Statements, &c., pp. 45 et seq. * ODA. Cltig, Pps 4554405 


136 ON ANAESTHETICS 


used in the same form at St. Bartholomew’s Hospital, in preference to sulphuric 
ether, by Mr. Lawrence in the summer of 1847.’ In the autumn of that year 
Dr. (afterwards Sir James Y.) Simpson, who was engaged in a series of experi- 
ments with various narcotic vapours, employed for the first time the active 
principle of chloric ether, at the suggestion of Mr. Waldie, of the Apothecaries’ 
Hall of Liverpool ;* and finding that the pure chloroform was more potent 
than sulphuric ether, yet caused less bronchial irritation, while its odour was 
more agreeable, and its inferior volatility rendered its exhibition more easy,* 
he zealously recommended it to the profession, and it has since been generally 
employed throughout Europe. 

The effects produced by chloroform are such as to fit it remarkably for the 
purposes of the surgeon. Like most narcotics, it tends to cause, after tem- 
porary excitement, suspension of the functions of the nervous centres, but 
affects them not simultaneously, but in a certain order; and the brain is the 
first to show loss of power in failure of sensation and voluntary motion. If 
this were all, anaesthesia would be a questionable boon, as the work of the 
surgeon would be interrupted and often marred by involuntary struggles on 
the part of the patient. But very soon the spinal cord also is subdued, and 
the reflex functions of the cerebro-spinal axis are abolished so far as concerns 
the voluntary muscles, which consequently lie perfectly relaxed and passive, 
better suited for operative purposes than the most resolute will could render 
them. To this, however, there is one remarkable exception, viz. that the parts 
concerned in the respiratory movements remain active; and the same is the 
case with the sympathetic ganglia of the heart. In other words, when the 
administration of chloroform is carried to a certain point, the nervous system 
is deprived of such powers as would cause pain to the patient or inconvenience 
to the surgeon, but retains intact the faculties essential to life. 

There are, however, yet other advantages derived from the inactivity of 
the cerebro-spinal centre. It seems now clearly established that the cessation 
of the contractions of the heart in the shock of injury depends upon an action 
of the brain and cord upon the cardiac ganglia through the medium of the vagus 
and sympathetic nerves; and chloroform, rendering this action impossible, 
protects the heart from the indirect effect of external violence. In this way 
it has greatly diminished the risk of death upon the operating table, and also 


* Snow on Anaesthetics, p. 20. That chloric ether was employed at St. Bartholomew’s Hospital 
has been further confirmed by information kindly communicated to me by Mr. (now Sir James) Paget. 

* Snow on Anaesthetics, pp. 21, 22; also Dr. Simpson’s original pamphlet, Account of a New 
Anaesthetic Agent, &c., p. 6. 

* For operations performed by artificial light, chloroform has another advantage over ether, in 
the fact that its vapour is not inflammable. 


ON ANAESTHETICS 137 


has overthrown the old rule of deferring amputation in cases of injury till the 
patient has recovered from the state of collapse, thus shortening the period 
of mischief to the system from the presence of the mangled limb, and in extreme 
cases sometimes saving life where it would be hopeless to wait for returning 
consciousness. Indeed, an amputation performed under chloroform has often 


the effect of improving instead of lowering the pulse. 

The most striking instance of this that has fallen under my notice occurred 
in a labourer, whose right arm and thigh had been destroyed by a railway acci- 
dent, just enough sound tissue being left to admit of amputation through the 
hip and shoulder joints, which was accordingly performed as a forlorn hope 
by the surgeon in charge of the case. The vital powers being in a state of 
extreme depression, it is probable that without chloroform this severe measure 
would have killed him outright, but by help of the anaesthetic it was followed 
by marked improvement of the pulse, which continued for some hours, so as 
to lead us to entertain hopes of his recovery. 


Faintness during the operation, a species of shock, is also got rid of by 
chloroform ; and this, besides its obvious convenience, has the advantage of 
lessening the chance of secondary haemorrhage ; for the vessels which require 
ligature declare themselves as such by bleeding, instead of deceptively eluding 
observation in consequence of the feebleness of the heart and the general arterial 
contraction which coexist in the state of syncope. 

The welfare of the patient is besides greatly promoted by the mental tran- 
quillity arising from the prospect of immunity from suffering, which also induces 
persons to submit much more readily to the necessary operations, and often to 
undergo without hesitation treatment which was formerly impracticable because 
intolerable. 

Such being the great benefits conferred by this agent, it is melancholy to 
reflect that in many parts of Europe, and even of the United Kingdom, it is 
either withheld altogether or given so scantily as to be nearly useless. This 
arises from fear, inspired by several fatal cases that have occurred. But when 
I state that Mr. Syme has given chloroform about five thousand times without 
ever meeting with a death, and that Sir J. Simpson’s experience, also very 
extensive, has, so far as I am aware, been equally satisfactory, it is clear that it 
may be used so as to be practically free from any risk whatever. 

How then are the fatal cases to be accounted for? Heart disease has 
been supposed to be a common cause of them; and it is a prevalent opinion 
that it is highly dangerous to administer chloroform to persons affected with 
cardiac disorder. 


It happens that the only death I ever witnessed under chloroform occurred 
in a person whose heart proved, on examination, to be extensively affected 


138 ON ANAESTHETICS 


with fatty degeneration, such as would be regarded as sufficient explanation 
of sudden death under any circumstances. The particulars of this case, how- 
ever, presented peculiar features, which lead me to take a different view of the 
part played by the chloroform from what might at first be assumed. The 
patient was a man above the middle period of life, affected with cancer of the 
penis, for which amputation of the organ was to be performed. The gentleman 
in charge of the chloroform, considering the momentary nature of the operation, 
purposely abstained from giving it as fully as usual, and had removed the cloth 
containing it from the face before the operation was commenced. The surgeon 
now placed his finger on the patient’s wrist, and having ascertained that the 
pulse was good, at once effected the amputation almost instantaneously. I 
observed that the passage of the knife through the member was accompanied 
by a start of the patient’s body ; the bandage used to controi the bleeding was 
then removed, but no blood flowed from the arteries; he was found to have 
no pulse at the wrist ; in short, he was dead. From these facts we can hardly 
doubt that death was a consequence of the shock of the operation acting on 
a diseased heart ; and the only question is whether the circumstance that he 
had taken chloroform promoted that result. From the foregoing considerations 
such a thing seems altogether improbable, as we have seen that chloroform 
protects the heart from the effect of shock. The fact that the patient started 
proved that reflex action was not abolished in the voluntary muscles, and con- 
firmed the statement of the administrator that the chloroform was imperfectly 
given. My own impression is, that 1f it had been pushed to the usual degree 
the fatal occurrence would have been averted. 


I have given this case in detail because I believe it may be regarded as 
typical of a considerable class in which death has taken place suddenly at the 
commencement of an operation with imperfect administration of chloroform, 
which stands to the fatal event in the relation of an accidental concomitant, or 
rather a preventive insufficiently used ?. 


A death essentially similar, though more obviously unconnected with 
chloroform, took place on the occasion when it was intended to have adminis- 
tered it for the first time in the Edinburgh Infirmary ; but Dr. Simpson being 
prevented from attending, the operation was commenced without the anaes- 
thetic, and the patient died suddenly immediately after the first incision. It 
has been often remarked that if the original intention had been carried out, 
chloroform would never have been heard of again in Edinburgh, but it is very 
likely that the man might then have lived to testify to its benefits. 


There is another class of fatal cases in which the use of chloroform seems 


* An observation made several years ago by Mr. Bickersteth, of Liverpool, has an interesting bearing 
upon this class of cases. He noticed on three occasions in amputation of the thigh that the pulse stopped 
suddenly at the moment the knife entered the limb, but recovered itself in a few seconds. The patients 
were under the influence of chloroform ; but as Mr. Bickersteth never observed the same thing again, 
though he watched the pulse carefully at the same period in a great number of capital operations under 
chloroform, it seems probable that the anaesthetic was not administered to its full degree in those 
instances. (See Monthly Journal of Medical Science, September 1853.) 


ON-ANAESTHETICS 139 


to have been simply a coincidence, the real cause of death being mental emotion, 
acting usually upon a disordered heart. 

Dr. Snow mentions a distinct example of this, where a mere profession of 
administering chloroform was made, and the patient died of fright ;! and I am 
able to give, from Edinburgh experience, an instance in which chloroform was 
still more remotely concerned. The late Dr. Richard Mackenzie, being called 
to see a gentleman who had fractured his radius, had some thought of employing 
chloroform in examining the arm, but, changing his mind, made the necessary 
manipulations without it. He then proceeded to leave the house, but had 
not got down the steps leading from the door when he was called back with the 
announcement that his patient had suddenly expired. 


Had chloroform been held near the face a few seconds before this occur- 
rence, it would certainly have been blamed, though with manifest unfairness 
and a similar injustice seems to have been committed with regard to several 
cases in which fatal syncope has taken place early in the administration of the 
anaesthetic, when the brief period of inhalation concurred with the symptoms 
in showing that the patient was little, if at all, under its influence. A fear of the 
chloroform itself seems to have been the exciting cause in some of these cases ; 
and one reason why no such instance has occurred in the Edinburgh Infirmary 
is probably the unlimited confidence reposed in this agent by the inmates of 
that institution. 

It might, perhaps, have been expected a priovt that chloroform, in the 
early or exciting stage of its operation, would act upon a diseased heart like 
mental emotion, and cause irregularity or cessation of its contractions. This, 
however, does not seem to be the case; and, judging from my own experience, 
I should say that it tends rather to remove intermission or irregularity of the 
pulse. On the whole I believe that chloroform, by preventing shock and mental 
effort during the operation as well as anxiety before it, is in reality a great source 
of safety in heart disease ; and that if a person with known cardiac affection 
decides to place himself in the hands of the surgeon, so far from being unsuited 
for the anaesthetic, he is before all others the man who stands most in need 
of its protecting influence. 

Nevertheless, even when the heart is perfectly healthy, it is quite possible 
to administer chloroform so as to produce a directly sedative and deadly influence 
upon the cardiac ganglia. This truth was deeply impressed upon me eight 
years ago by the following occurrence. 

An eminent London physician, desirous of making some experiments upon 


the heart, selected a young donkey for the purpose, and. “requested me to maintain 
artificial respiration, which was done by means of a large pair of bellows con- 


* Snow on Anaesthetics, p. 201. 


140 ON ANAESTHETICS 


nected with a tube tied into the trachea, the animal having been previously 
put under the influence of chloroform. The chest having been opened, the 
investigation was continued for a while, when the creature began to exhibit signs 
of returning consciousness. To avert this I removed the bellows, and poured 
into them a considerable quantity of chloroform, and resumed the artificial 
respiration with energy for a short time, the natural respiratory movements 
meanwhile continuing ; when suddenly the heart, which lay exposed before us, 
ceased to beat, and refused to contract again even when its muscular substance 
was pinched, which showed that its nervous apparatus was paralysed. 


This was no doubt caused by the air becoming highly charged with chloro- 
form in passing over the extensive evaporating surface presented by the interior 
of the bellows. For it had been before shown by Dr. Snow, from experiments 
upon the lower animals, that an atmosphere containing more than a certain 
percentage of the narcotic vapour stops the heart before breathing ceases, 
whereas the reverse occurs when the chloroform is more diluted with air.! 
Hence, with the view of preventing fatal syncope, Dr. Snow contrived an inhaler 
for regulating the amount of chloroform vapour in the inspired air, and used 
it in upwards of four thousand cases, of which only one was fatal, and even 
that seemed to be so independently of the chloroform. Finding his ingenious 
efforts crowned with such success, and charitably supposing that all were as 
careful as himself, he concluded that fatal cases in the hands of others could 
result only from a faulty method of administration ; and assuming that when 
chloroform is given from a folded cloth it is apt to be in too concentrated a form, 
he attributed most of the deaths that have occurred to paralysis of the heart 
from this cause. | 

But the cloth being the means which has been used from the first in Edin- 
burgh, with success even superior to Dr. Snow’s, I have been long satisfied 
that his argument was fallacious; yet as his special devotion to the subject, 
and the valuable facts which he has communicated regarding it, render his 
opinion influential, I have thought it worth while to subject a matter of such 
great practical importance to experimental inquiry; and, about the usual 
quantity of the liquid being employed, I find that, so far from the amount of 
chloroform given off from the cloth being in dangerous proportion to the air 
inhaled, the whole quantity which evaporates from the under surface, even 
when the rate is most rapid, viz. just after the liquid has been poured upon it, 
is below Dr. Snow’s limit of perfect security against primary failure of the heart.” 

* I have noticed, however, that different animals differ in their susceptibility to chloroform. Thus 
frogs or mice may be kept for any length of time under its influence ; but bats are very apt to die when 
treated in exactly the same way. 


* The experiments were performed in the following manner: A cloth, similar in all respects to what 
would be used in practice, was supported upon a light wire framework, and suspended at a little distance 


ON ANAESTHETICS 141 


But, considering the great diffusibility of the vapour, and the large amount 
blown away in expiration, it is evident that only a small proportion of that 
which comes from the lower surface of the cloth really enters the lungs. Were 
it otherwise, it would be extremely dangerous to give chloroform with the cloth 
to infants, for as they inhale but a small amount of air, they would then breathe 
the vapour in a very concentrated state; yet all are agreed that infants are 
peculiarly favourable subjects for chloroform. In truth, the quantity dissipated 
into the surrounding air when the cloth is used involves considerable wastefulness 
in this means of administration, which is its only disadvantage as compared 
with an inhaler, but this is abundantly compensated by its greater simplicity, 
and consequent greater safety. For any apparatus which has the effect of pre- 
venting the free access of the atmosphere must be liable to operate in the same 
deadly manner as the bellows in the case above related, and even when con- 
structed upon the best principles, it will require most careful management, as 
is admitted by Dr. Snow with regard to his own inhaler.t. On the other hand, 


from the floor by a thread, connected with one end of the beam of a balance, projecting over the edge 
of the table on which it stood. The weight of the cloth having been ascertained, a weighed quantity 
of chloroform, corresponding to fl. 4jss., which is about the amount commonly used, was poured upon 
the middle of the lower surface of the cloth, which was then allowed to hang close above my face, so that 
I might breathe fully upon it, while inspiration was performed through a long india-rubber tube to avoid 
inhaling the chloroform vapour. The amount lost by the cloth was indicated by the weights in the scale 
at the other end of thebeam. At the commencement of an experiment the weight was made a few grains 
less than the sum of the weights of the cloth and chloroform together, and an assistant noted the second 
when the scale with the weights in it came to preponderate; then removed ten grains so as to allow the 
scale to rise, and again watched the time of its descent ; and repeated this process several times, thus 
obtaining a very accurate record of the rate of alteration in the weight. The lower surface of the cloth, 
which was made slightly concave, was circumstanced just as in the early period of the administration 
of chloroform, except that the inspired air was drawn from a distance. Inspiration does not, however, 
materially affect the rate of evaporation, as was found by experimenting with a cloth arranged above 
the mouth of a tube into which air was drawn by an appropriate apparatus. Allowance being made 
for the slight gain in weight that the cloth would obtain from absorbing moisture from the breath, 
the amount of chloroform lost from both surfaces together was thus easily determined. In order to 
ascertain how much escaped from the upper surface, experiments were made with the same cloth, having 
first the upper and then the under side securely covered with oil-silk, the arrangements being as above 
described, except that my face was not below the cloth. The quantity given off from the upper surface 
in a normal atmosphere was thus determined; and this being subtracted from the whole loss from 
both surfaces under the circumstances of inhalation, gave the amount that evaporated from the lower 
surface only. Atthe temperature of 70° Fahr. this proved to be, from the average of several experiments, 
at about the rate of 24 grains per minute during the first half-minute ; and allowing, with Dr. Snow, 
that 20 grains of chloroform correspond to 15-3 cubic inches of the vapour, and that 400 cubic inches 
of air are inhaled in a minute, we get 4:5 per cent. as the proportion of the chloroform to the inspired 
air, on the hypothesis that all that evaporates from the lower surface enters the lungs; 5 per cent. 
being what Dr. Snow was led by his experiments to regard as the proportion at which the respiration 
was quite sure to fail before the circulation, and that at which he aimed with his inhaler (op. cit., p. 34). 
On the other hand, Dr. Snow assumed that, when the cloth is used at a temperature of 70° Fahr., 
9:5 per cent. of chloroform is really inhaled (op. cit., p. 34) ; whereas, in truth, of the 4-5 per cent. a large 
amount is dissipated into the surrounding air. 
+ Op..CIt.. pp. Tél, 188. 


142 ON ANAESTHETICS 


there can be no mistake about the manner of using the cloth, which is also 
always at hand under all circumstances. 

The theory of syncope from too great strength of the anaesthetic vapour 
when the cloth is employed being erroneous, the greater number of the deaths 
still remain unaccounted for; and, if we except a very few instances for which 
we seem to have nothing to fall back upon but an idiosyncrasy so rare that 
it may practically be left out of consideration altogether, their explanation 
will, I believe, be found in an overdose of this potent narcotic from too long 
continued administration. 

This is what might be expected from a general view of the statistics. Were 
we to ask ourselves in what sort of operations we should have anticipated most 
frequent deaths during the employment of chloroform, we should say in those 
which are likely to inspire great dread on account of their magnitude and 
severity, and to cause great shock and great haemorrhage. More especially 
should these preponderate among fatal cases in general hospitals, where serious 
operations constitute the majority of those performed. The reverse of this, 
however, is what we actually find. Of the whole number of cases recorded 
by Dr. Snow in 1858, as due to the use of chloroform throughout the world 
during ten years, nine only occurred in any considerable surgical procedure 
at a general hospital; remarkably few, considering the enormous number of 
important operations that must have been performed during so long a period, 
and the variety in the qualifications of those who administered the chloroform. 
On the other hand, fourteen took place at similar institutions in connexion 
with the most trivial matters, such as the removal of a toe-nail, the amputation 
of a finger, the passing of a catheter, or the cauterizing of a wart. The only 
rational explanation of this seems to be, that when some great operation is 
to be performed, like the amputation of a thigh or the removal of a stone from 
the bladder, plenty of well-qualified assistants are present, and each of them, 
including the giver of the chloroform, is duly impressed with the importance 
of his office, and bestows the requisite pains upon it. But when some trifle 
is to be done, the whole affair is apt to be regarded too lightly, and the adminis- 
tration of the anaesthetic is perhaps confided to some unsuitable person, who 
also allows his attention to be distracted by other matters. This conclusion 
is entirely in accordance with my own experience, which, while it has convinced 
me more and more of the safety of chloroform if properly given, has impressed 
me deeply with the necessity for more vigilant care in its employment than is 
sometimes apt to be bestowed. 

But an overdose of chloroform may be caused by attention misapplied, 
as well as by want of attention. The requisites for safety in using it will be 


ONTANAESTIMETICS 143 


best introduced by a short account of what ordinarily occurs in the mode of 
administration with which I am most familiar. A common towel being arranged 
so as to form a square cloth of six folds, enough chloroform is poured upon it 
to moisten a surface in the middle about as large as the palm of the hand, the 
precise quantity used being a matter of no consequence whatever. The patient 
having been directed to loosen any tight band round the neck, and to shut 
his eyes to protect them from the irritating vapour, the cloth is held as near 
the face as can be comfortably borne, more chloroform being added occasionally 
as may be necessary. After a time, varying considerably in different individuals, 
but generally longest in adults who have been accustomed to the free use of 
narcotics, and shortest in young children,’ signs of excitement begin to manifest 
themselves in various ejaculations and muscular efforts, which soon give place 
to a state of complete repose. The struggles of the patient are sometimes so 
violent as to require considerable force to restrain them, and, for this reason, 
at least one efficient assistant should always be in attendance. On the other 
hand, I have seen chloroform induce nothing but a tranquil slumber ; and it is 
important to bear in mind that the stage of excitement cannot be reckoned on 
as invariably declaring itself at all. 

The most convenient test of the patient being prepared for undergoing the 
operation is presented by the eye ; not in the size of the pupil, which is incon- 
stant in its indications, but in what is commonly spoken of as insensibility of 
the conjunctiva, though in truth it has no relation to sensation, which is 
abolished considerably earlier ; but when unconscious winking no longer occurs 
on the eyeball being touched with the tip of the finger, we have a good criterion 
of the suspension of reflex action in the body generally. At this period the 
pulse is in about a normal condition, and the respiration is usually either natural 
or very slightly stertorous, though persons with a strong tendency to snore 
may do so almost from the commencement of inhalation. But if the adminis- 
tration of the chloroform be further persisted in, strongly stertorous breathing 
will soon be induced, and will become aggravated till it passes into complete 
obstruction to the entrance of air into the chest, though the respiratory move- 
ments of the thoracic walls still continue. Occasionally, however, the pre- 
monitory stertor is deficient, and the breathing becomes more or less suddenly 
obstructed. This is a point of great importance, for without close attention 


1 IT once met with an instance in which chloroform seemed incapable of affecting a patient. It 
occurred in the private practice of Mr. Syme, who was about to perform an operation, for which we 
proceeded to administer the anaesthetic ; but after we had used the cloth till we were tired without 
any apparent effect, Mr. Syme went on with the operation while the patient was conscious. Such 
a case is, no doubt, excessively rare,’ but it is interesting as giving some colour to the hypothesis that 
idiosyncrasy in the opposite direction has existed in some very few fatal cases, which seem to admit 
of no other explanation, as alluded to in the text. 


144 ON ANAESTHETICS 


it may escape notice, when the patient will be placed in imminent peril. For 
though the respiration may be resumed spontaneously, this cannot be relied on, 
and it would seem that when chloroform is given in an overdose, the cardiac 
ganglia are apt to become enfeebled ; and on this account asphyxia produces 
more rapidly fatal effects under its influence than in ordinary circumstances. 
But if the obstructed state of the breathing is noticed as soon as it occurs, and 
the cloth is immediately removed from the face, and the tip of the tongue seized 
with a pair of artery forceps’ and drawn firmly forwards, the respiration at 
once proceeds with perfect freedom, the incipient lividity of the face is dispelled, 
and all is well. 

I am anxious to direct particular attention to the drawing out of the tongue, 
because I am satisfied that several lives have been sacrificed for want of it. 
In order that it may be effectual, firm traction is essential. I have, more than 
once, seen a person holding the end of the organ considerably beyond the lips 
without any good effect, and, placing my hand on his, have given an additional 
pull that has re-established the respiration. 

A simple experiment, which any one may perform upon himself, is illustra- 
tive of this point. Stertorous breathing, such*as occurs under chloroform, 
may be produced at will, and may be carried on even while the tongue is pro- 
truded to the extreme degree. But if the tongue is laid hold of with a handker- 
chief and pulled so as to cause decided uneasiness, stertorous breathing of any 
kind becomes impossible. That further traction, when extension already exists 
to the utmost, should produce such an effect is an apparent anomaly which it 
seemed important to explain. On investigating the subject, I noticed in the 
first place that stertorous breathing is of two essentially different kinds, of 
which one, that may be called palatine, consists in vibrations of the velum, 
and has either a buccal or nasal character, according as the air passes through 
the mouth or the nose ; while the other, which is the profound stertor essentially 
concerned with chloroform, depends on a cause seated further down the throat, 
and, for reasons to be given immediately, may be termed laryngeal. By digital 
examination of my own throat I found that the latter variety, and the com- 
plete obstruction into which it passes, could still be produced when the tongue 
was separated by a considerable interval from the back of the pharynx, while 
a free passage for the air existed onwards to the lips, which showed that the 
general belief, that the obstruction depends on a ‘falling back of the tongue’, 
is erroneous. Also the epiglottis, instead of being folded back during the 


* The artery forceps are the most convenient means of drawing the tongue forwards. The puncture 
which they inflict is of no consequence ; the patient, if he notices it at all, supposes that he has bitten 
his tongue when under the chloroform. 


ON ANAESTHETICS 145 


obstruction, as some have supposed, had its anterior edge directed forwards : 
and though it was thrown into vibrations when the stertor was strongest, it was 
evident that the cause of the sound was more deeply placed. I also found that, 
although firm traction upon the tongue abolished the obstruction and the stertor, 
it did not appear to produce the slightest change in the position of the base 
of the tongue ; nor did it move the os hyoides upon the thyroid cartilage, as 
examined from without. Hence I was led to conclude that the beneficial effect 
of this procedure could not be explained mechanically, but must be developed 
in a reflex manner through the medium of the nervous system. The fact that, 
when sensation is perfect, some degree of pain is caused in the process, implying 
an irritation of the nerves, was in favour of this view ; while the general abolition 
of reflex action by chloroform did not seem strongly opposed to it, considering 
that the reflex respiratory movements, including those of the glottis, go on in 
a person under the influence of chloroform. 

For further elucidation of the matter I had recourse to the laryngoscope ; 
and, after a little patience, found no difficulty in inspecting my own vocal ap- 
paratus without employing any depressor of the tongue, using simply the small 
oblique long-handled speculum and a common mirror in bright sunlight. I then 
ascertained that the true laryngeal stertor results from the vibration of the 
portions of mucous membrane surmounting the apices of the arytaenoid cartilages, 
i.e. the posterior parts of the arytaeno-epiglottidean folds (thick and pulpy in 
the dead body, but much more so when their vessels are full of blood), which are 
carried forwards to touch the base of the epiglottis during the stertorous breath- 
ing, and are placed in still closer apposition with it when the obstruction becomes 
complete. Having one hand at liberty, I was able to observe the effect of 
drawing forward the tongue under these circumstances, and I saw that firm 
traction induced the obstructing portions of mucous membrane in contact with 
the epiglottis to retire from it for about an eighth of an inch, so as to allow free 
passage for the air, while the epiglottis itself was not moved forwards in the 
slightest degree. 


* While the true laryngeal stertor was thus produced and thus removed, a sort of spurious snoring 
might be made by approximation of the vocal cords; but this spurious stertor was, like the voice, 
quite unaffected by drawing out the tongue. These observations were made on September 21 of the 
present year (1861). I find that there are four ways in which the passage through the larynx may be 
closed. First, the folding back of the epiglottis over the opening into the pharynx, as is generally 
believed to take place in swallowing, and may be demonstrated by arresting an act of deglutition in 
its progress, and insinuating the finger between the tongue and the roof of the mouth to the epiglottis, 
which is then felt to be turned backwards, and to return to its usual position as the act of deglutition 
is finished. Secondly, an approximation of the szdes of the superior orifice of the larynx, in which the 
epiglottis is directed forwards, but folded longitudinally, so that its edges are in contact with one 
another while the arytaeno-epiglottidean folds are also in lateral apposition. [Note written in April 
1908: This fact was observed in the retching caused by the application of a solution of nitrate of silver 

LISTER I L 


146 ON ANAESTHETICS 


Whether pulling the tongue operates by inducing or relaxing muscular 
contraction in the larynx may be matter for discussion, but the main con- 
clusion, that it does not act merely mechanically, but through the nervous 
system, appears satisfactorily established. I have not hesitated to give the 
evidence on which it rests in full, as it appears to me to be of the highest practical 
moment. For it shows at once how grievous a mistake is committed by those 
who content themselves with gently drawing the apex of the tongue a little 
beyond the teeth, or pushing forward its base with the finger, or perhaps ascer- 
taining that the epiglottis is not folded back. Such proceedings are instances 
of attention misapplied, and waste the golden opportunity for rescuing the 
patient from death. The proper treatment, like many other good things in 
medical practice, owes its origin to a false theory, but though the erroneous 
notion of obstruction by the tongue did good service in the first instance by 
suggesting the original method, it now tends to encourage supposed improve- 
ments upon it, which rob it entirely of its efficacy. 

If the above description is correct, if it is true that when the administration 
of chloroform with the cloth is carried too far, the first serious symptom is an ob- 
structed state of the respiration, which without watchful care mayoccur unnoticed, 
and, if allowed to continue, will endanger the life of the patient, but, if promptly 
treated, will harmlessly disappear—it follows that the attention of the adminis- 
trator ought to be concentrated on the breathing, instead of being, as it too 
often is, diverted by the pulse, the pupil, or other matters still less relevant. 


As an example of the risk that is run by want of close attention to the 
respiration I may mention the following case. A surgeon of considerable 
experience was giving chloroform to a patient on whom an operation was being 
performed, of which I was a mere spectator, but I noticed that stertorous 
breathing came on, and gradually passed into complete obstruction, at a time 
when the administrator was gazing with interest upon the proceedings of the 
operator. Seeing that the patient was in danger, I suggested to the giver of 
the chloroform the propriety of pulling forward the tongue. He replied that 
this was uncalled for, and pointed to the heavings of the chest as evidence that 


to the larynx of a patient. I find that it is not universally recognized.] This occurs in retching, 
and doubtless also in vomiting, when a folding back of the epiglottis, instead of protecting the larynx, 
would tend to direct into it the material passing from below upwards. Thirdly, an antero-posterior 
coaptation of the structures of the laryngeal aperture at a somewhat deeper level, without any change 
in the position or form of the epiglottis, towards which the folds of mucous membrane above the apices 
of the arytaenoid cartilages are carried forwards, till they are in contact with its base. This is seen 
in coughing, and also in laryngeal stertor; and it is probable that during sleep, when the respiration 
is so apt to become stertorous, there is but a very narrow chink between the epiglottis and these folds 
of mucous membrane, which would thus serve to protect the deeper parts of the air-passages from the 
introduction of foreign matters in the state of unconsciousness. Fourthly, the closure of the 71ma 
glottidis in the production of voice. The white chordae vocales form a beautiful contrast with the highly 
vascular structures in their vicinity. 


ON ANAESTHETICS 147 


breathing was proceeding freely. Knowing from what had gone before that 
those efforts were doing nothing for the respiratory function, and feeling that 
there was no time for discussion, I stepped out of my province so far as to seize 
the tongue myself and draw it forward, when a long and loudly stertorous in- 
spiration demonstrated the necessity for the interference. Had the delusive 
movements of the chest been trusted, it is probable that they might have con- 
tinued till the heart had become so enfeebled by the asphyxial state as to cause 
no perceptible pulse at the wrist ; and had death occurred under these circum- 
stances, the case would have been set down as one in which the circulation failed 
before the respiration. The administrator would thus have been absolved from 
all blame, and the fatal event would have been attributed to idiosyncrasy, or to 
any heart disease which might have been discovered on post mortem inspection. 

The very prevalent opinion that the pulse is the most important symptom 
in the administration of chloroform is certainly a most serious mistake. As 
a general rule, the safety of the patient will be most promoted by disregarding 
it altogether, so that the attention may be devoted exclusively to the breathing. 
The chance of the existence of heart disease may seem to make this practice 
dangerous, but having followed it myself with increasing confidence for the 
last eight years, and knowing that it has been pursued all along by Mr. Syme, 
who has also acted on the maxim that every case for operation is a case for 
chloroform, and must, therefore, have given it to very many patients in whom 
cardiac disorder existed unknown to him, besides some in whom its presence 
had been ascertained, I feel no hesitation in recommending it. Even when 
serious disease of the heart is known to exist, it must be remembered that there is 
much less risk of syncope than of obstruction to the respiration; and while 
the latter will demand and repay immediate attention, the former, should it 
by any chance occur, being in all probability independent of any excess of 
chloroform, would not imperatively demand its discontinuance ; nor would it 
be much influenced by treatment, supposing the patient to be already in the 
horizontal posture, which is generally considered safest in all cases when chloro- 
form is given. 

From these considerations it appears that preliminary examination of the 
chest, often considered indispensable, is quite unnecessary, and more likely to 
induce the dreaded syncope, by alarming the patient, than to avert it. 


* From the views expressed in the text regarding the relation of syncope to the administration 
of chloroform, it might be inferred that no great danger would be incurred by giving it in the sitting 
posture when circumstances particularly require it; and accordingly Dr. Snow informs us that he 
has done this on several occasions without any bad result. But considering the possibility of an over- 
dose, and the feebleness of the heart which that seems to entail, it is no doubt wisest, as a general rule, 
to have the patient reclining. Dentists, it is true, give chloroform in the sitting posture; but, so far 
as I have seen, they do not carry the administration beyond a slight degree, sufficient to deaden sensa- 
tion without affecting reflex action, dexterously managing to open the mouth and operate upon it 
while the muscles of the jaws are rigid. 

L2 


148 ON ANAESTHETICS 


The obstructed state of the breathing, if allowed to continue long, would 
lead to a far more serious affection—paralysis of the nervous centre concerned 
in the respiratory movements. Pulling out the tongue would then of course 
have no good effect of itself, but it should be done to clear the way for artificial 
respiration, which is the means to be essentially trusted to under such circum- 
stances ; and if the air still fail to enter freely into the chest, an opening ought 
to be made without delay through the crico-thyroid membrane. Cold water 
should also be occasionally dashed upon the face and chest ; and if a galvanic 
battery happen to be in readiness, one of its poles may be applied over the 
spinous processes of the upper cervical vertebrae, and the other to the prae- 
cordial region, with the object of rousing the respiratory and cardiac ganglia. 
This, however, is a means not very likely to prove beneficial, and if used in too 
intense a form it may do harm instead of good. 

Preparatory to taking chloroform the patient should be directed to omit 
the last meal which would naturally precede it,.as any food in the stomach is 
almost sure to give rise to troublesome vomiting during the inhalation. The 
only after-treatment necessary is to allow the effects of the chloroform to pass 
off ina quiet sleep ; and the only bad consequence likely to arise is a tendency 
to sickness, which sometimes causes annoyance during the first twenty-four 
hours or so." 

Chloroform is universally applicable in the various departments of surgery, 
except in some few cases in which the assistance of the patient is required, and 
in operations involving copious haemorrhage into the mouth. Blood may 
trickle in small amount into the pharynx without risk of choking, deglutition 
being carried on unconsciously during anaesthesia ; and even in some instances 
when the bleeding is more serious, as in removing portions of the jaws, pain 
may be avoided to a great extent by giving the chloroform during the more 
superficial parts of the operation, and allowing the patient to recover partially 
before undertaking its deeper stages. 

The main conclusions arrived at in this article may be expressed in a few 
words. It appears that chloroform, though resembling many other valuable 
means of treatment in being deadly when mismanaged, is free from danger 


1 It has been supposed by some that the use of chloroform increases the risk of pyaemia after 
capital operations ; but experience has now abundantly proved the groundlessness of this apprehension. 
To take a single instance, the veins of the pelvic viscera being perhaps, next to those of the bones, more 
liable than any others to originate phlebitis after surgical interference, lithotomy would be much more 
fatal now than formerly were there any foundation in fact for the notion. The reverse, however, 
appears to be really the case. Thus, Mr. Cadge, one of the surgeons of the Norfolk and Norwich Hospital, 
an institution long celebrated for the successful treatment of stone, in a district abounding in calculous 
disease, informs me that the mortality after lithotomy has been still further reduced there since the 
introduction of chloroform. 


ONT ANAESTHETICS 149 


if properly used, the following being the rules for its safe administration. 
A drachm or two of the liquid having been sprinkled upon the middle of a 
folded towel, hold it near the face, taking care that free space is afforded for 
the access of air beneath its edges, till the eyelids cease to move when the 
conjunctiva is touched with the finger. Meanwhile watch the breathing care- 
fully ; and if at any time it should become obstructed or strongly stertorous, 
suspend the administration and draw the tip of the tongue firmly forwards till 
the tendency to obstruction has disappeared. 

These simple instructions may be acted on without difficulty by any intel- 
ligent medical man. The notion that extensive experience is required for the 
administration of chloroform is quite erroneous, and does great harm by weaken- 
ing the confidence of the profession in this valuable agent, and limiting the 
diffusion of its benefits. 


ParT II. WRITTEN 1870 


The nine years which have passed since the above article was written have 
tended to confirm its main doctrines. 

The safety of chloroform when administered according to the rules laid 
down in the preceding pages has hitherto been verified without exception in 
my own personal experience ; and I may add that Mr. Syme, though he con- 
tinued to within the last two years in the full activity of his career as an operator, 
never lost a patient through its use, either in public or private practice. Further, 
I believe I am correct in stating that no case of death from chloroform has 
occurred during these nine years in the operating theatre of either the Edin- 
burgh or the Glasgow Infirmary, two of the largest surgical hospitals in Great 
Britain. Yet in both these institutions a folded towel on which the anaesthetic 
liquid is poured, unmeasured and unstinted, is still the only apparatus employed 
in the administration ; preliminary examination of the heart is never thought 
of, and during the inhalation the pulse is entirely disregarded; but vigilant 
attention is kept upon the respiration, and, in case of its obstruction, firm traction 
upon the tongue is promptly resorted to. And it is worthy of special notice, 
as showing that success is due to soundness of the principles acted on, rather 
than any particular skill, that the giving of the chloroform, instead of being 
restricted to a medical man appointed for the function, as is elsewhere often 
thought essential, is entrusted to the junior officers of the hospital. In Edin- 
burgh each of the five surgeons has two ‘clerks’, intermediate in position 
between the house surgeon and the dressers. They, besides other duties, take 
it in turn to administer the anaesthetic ; and if I had to be placed under its 


150 ON ANAESTHETICS 


influence I would rather trust myself to one of these young gentlemen than to 
the great majority of ‘ qualified practitioners ’. 

The appointment of a special chloroform-giver to a hospital is not only 
entirely unnecessary, but has the great disadvantage of investing the adminis- 
tration of chloroform with an air of needless mystery, and withholding from 
the students the opportunity of being trained in an important duty, which any 
one of them may be at once called upon to discharge on commencing practice, 
and which, though certainly simple, is better performed after some practical 
initiation. I well remember the anxiety I felt on entering upon office as Mr. 
Syme’s house surgeon, though I had before held a similar position in London, 
lest his first fatal case should occur in my hands; but this feeling soon gave 
place to perfect confidence, more especially after I had seen symptoms, which 
would before have alarmed me, dispelled at once by traction on the tongue, 
which was then a novelty to me, and which is, I fear, even yet not duly appre- 
ciated by the profession generally. 


An incident which occurred during my Glasgow incumbency illustrates so 
strikingly both the value of drawing forward the tongue, and the relations of 
the circulation and the respiration to chloroform, that 1t seems right to place 
it on record. One of my colleagues in the Infirmary had been making an 
attempt to reduce a dislocation by means of the pulleys, chloroform having 
been given very fully by the house surgeon, who, at the close of the perfor- 
mance, removed the cloth from the patient’s face, and proceeded to attend to 
other matters. Happening to be present, and observing that the respiration 
was deeply stertorous, I watched it carefully, and noticed that it passed almost 
immediately into the state of complete obstruction, though still accompanied 
by the movements of the thorax, the face meanwhile becoming markedly livid. 
Unwilling to interfere, and seeing the carotid pulsation conspicuous in the neck, 
I waited awhile, hoping that the obstacle to the breathing would disappear 
spontaneously. But instead of this I soon saw to my horror the lividity give 
place to what I knew was physiologically identical with post mortem pallor. 
I now rushed forward and drew the tongue out firmly with the artery forceps ; 
air at once passed into the chest, and the man was rescued. 


This case seems to me fraught with the deepest instruction. 

There can be no doubt that the patient was on the very verge of death ; 
that if the laryngeal obstruction had lasted a very short time longer, the respira- 
tory and cardiac ganglia would have failed in their functions. Supposing the 
administrator to have continued the chloroform with his attention devoted to 
the circulation, the first thing that would have alarmed him would have been 
the failure of the pulse at the wrist. On removing the cloth from the face, 
he would have seen the deadly pallor, and, ignorant of the asphyxial lividity 
which had preceded, he would have taken it as positive evidence of primary 


ON ANAESTHETICS I51 


failure of the heart, a verdict in which the whole profession would probably 
have supported him, whether valvular disease or fatty fibres could or could 
not be discovered on post mortem inspection. The case, then, reads us another 
striking lesson on the paramount importance of taking the respiration as our 
guide, and shows how readily, if this be not done, a death due to the grossest 
mismanagement may be regarded as the inevitable result of constitutional 
peculiarity. 

The case also shows the necessity of keeping watch for a while after the 
administration has been discontinued. The last portions of the vapour inhaled 
seem to take some seconds at least before they produce their full effects on the 
nervous centres; and the patient should not be left till he has been seen to 
breathe calmly and freely for some minutes after the cloth has been removed. 

On one occasion only, so far as I remember, have I seen firm traction on 
the tongue fail to remove laryngeal obstruction. In that instance the chest 
continued to heave, but no air entered or escaped, although the tongue was 
well drawn out. Happily, however, the desired effect was instantly produced 
by slapping the face with a towel dipped in cold water, while the traction on 
the tongue was maintained. This fact is interesting, not only as a striking 
illustration of the value of the sudden application of cold under such circum- 
stances, but also because it confirms the explanation before given of the modus 
operandi of traction on the tongue, viz. that it operates not mechanically, but 
through the nervous system. For here the barrier to the entrance of air into 
the chest remained in spite of the clearing away of any obstacle which the tongue 
might be supposed to present, but that barrier was at once removed by a means 
which could not act in any other way than through the nerves. 

It is nevertheless true that the tongue does frequently fall back under 
chloroform, and so occasion a mechanical impediment to respiration. It recedes, 
no doubt, in consequence of relaxation of the lingual muscles ; and accordingly 
thick or obstructed breathing depending on this cause may be very simply 
cleared by pulling the beard or forcibly pushing up the chin, so as to draw for- 
ward the tongue through the medium of the muscular fibres which pass back 
to it from the maxilla. Turning the patient’s face well round to one side, so 
as to cause the weight of the relaxed organ to tell laterally rather than back- 
wards, is another way in which a needless puncture of the tongue may often 
be avoided. But it must always be borne in mind that neither of these means 
can be expected to succeed if the obstruction exists in the larynx, and if they 
do not answer their purpose, not a moment should be lost in applying the artery 
forceps. 

Whenever it is necessary to draw the tongue forward, it is of course equally 


152 ON ANAESTHETICS 


needful to suspend the administration, by taking the cloth entirely away from 
the neighbourhood of the face. To act otherwise would be to pour in a fatal 
dose after artificially removing the natural safeguard against its entrance. To 
give a caution against so obvious a breach of physiological principle may seem 
superfluous, but I know by experience that it is not uncalled for. 

I have admitted in the foregoing article that idiosyncrasy may have been 
the cause of death in some anomalous cases which have been put on record. 
We certainly see strange varieties in the effects produced by chloroform both 
on the cerebral and the spinal centres. Some persons when inhaling it le from 
first to last as in a tranquil slumber ; some, before they succumb to its narcotic - 
influence, struggle with great violence, without uttering a sound; others bawl 
lustily, while some sing sweetly, and others again are disposed to converse quietly 
though incoherently with those around them. There are also remarkable 
differences in the relation of sensation to consciousness under chloroform. As 
a general rule they are affected simultaneously, but we now and then see patients 
insensible to the pain of an operation, though perfectly conscious of all that is 
passing. Equally various are the effects upon the spinal functions. The 
absence of winking when the eyeball is touched with the finger, though a very 
good general guide to the abolition of reflex action in the body generally, is 
by no means an unvarying indication. In some persons that particular function 
is abolished earlier or later than usual. Relaxation of the sphincters of the 
bowel and bladder is a result of chloroform happily only occasionally met with, 
and various other instances of exceptional phenomena might be mentioned. 
Another example of peculiarity, more closely bearing upon the question of 
death from chloroform, has come under my observation in two instances during 
the last nine years, viz. cessation of the movements of the thorax, or in other 
words suspension of the function of the respiratory ganglia, without any pre- 
liminary laryngeal obstruction, although there was not, so far as I could judge, 
anything unusual in the mode of administration. In both cases natural breath- 
ing soon returned under artificial respiration maintained by intermitted pressure 
on the false ribs, while the tongue was drawn forward, accompanied by occasional 
slapping of the face and chest with a cold wet towel. But the condition was 
sufficiently alarming while it lasted. The patients were both elderly, feeble 
subjects, and I may remark that if I ever give chloroform with any degree of 
apprehension, it is to the aged and infirm. 


Another closely allied instance of idiosyncrasy once presented itself in my 
practice. I had removed under chloroform a small epithelial cancer from the 
eyebrow of a feeble old woman, nothing unusual having occurred, when I noticed 
that the breathing assumed a peculiar sighing character, and the intervals 


ON ANAESTHETICS 153 


between the sighs became greater and greater, till I began to fear their entire 
cessation. However, normal respiration returned, and in the course of a few 
minutes she got up and sat in a chair beside the fire. But she had not been 
there long before the same strange slow breathing came on again, as if she would 
sigh her life away, and I believe that if I had not had her put back promptly 
to bed she would actually have died. Here a feeble frame was further weakened 
by the potent narcotic, and it happened that the effect told especially upon 
the respiratory function, with the peculiarity that it was manifested not during 
the administration of the chloroform, but subsequently. 


With these examples before us of deviations from the usual order in which 
the various functions of the nervous system are affected by chloroform, no one 
can say it is impossible that here and there an individual may be found so con- 
stituted that, without any undue proportion of the narcotic vapour to the air 
inhaled, the cardiac ganglia may fail before the respiration is interfered with. 
But while freely admitting that such a thing is possible, I must repeat my firm 
conviction that this kind of idiosyncrasy is certainly ‘so rare that it may practi- 
cally be left out of consideration altogether ’. 

The danger of chloroform may be compared, not inaptly, to that of railway 
travelling. In both cases the risk incurred by any individual is so small that 
it does not enter seriously into our calculations. And just as railway accidents 
are generally occasioned by culpable mismanagement, so death from chloroform 
is almost invariably due to faulty administration. 

Various attempts have been made during the last nine years to improve 
our anaesthetic methods. Among these must be mentioned the reassertion of 
the claims of sulphuric ether by the late Dr. Mason Warren, of Boston, in 
America. Our transatlantic brethren naturally feel indignant that their grand 
discovery of anaesthesia in surgery should be confounded with the very secondary 
matter of finding out that a different agent from that which they employed 
will produce similar effects in a more efficient manner. For the introduction 
of chloroform, when the whole subject was a novelty, led to a confusion in the 
public mind in this country, where ‘the discovery of chloroform’ is often re- 
garded as identical with the discovery of anaesthesia. And there can be no 
doubt that if sulphuric ether were still in use in Britain as it is in Boston, and 
if chloroform were now brought forward for the first time as a substitute for it, 
comparatively little would be thought of the innovation. More convenient 
chloroform undoubtedly is, on account of its smaller bulk, and the greater 
facility of its administration, but Dr. Warren contended that these advantages 
were more than counterbalanced by the greater safety of ether, which he declared 
had never up to the time of his writing produced a single death." Admitting 


* See Surgical Observations, with Cases and Operations, by J. Mason Warren, M.D., &c. 


154 ON ANAESTHETICS 


the facts to be in the main as Dr. Warren has given them, the case may probably 
be fairly stated by saying that ether, being less potent, is less liable to cause 
death from mismanagement. But the rules for the satisfactory use of chloro- 
form are so simple that mismanagement is really inexcusable ; and if we had 
nothing else to consider than the question of safety, chloroform would probably 
in all cases maintain its superiority over ether. There is, however, another 
point in which a great advantage has been lately claimed for the original anaes- 
thetic. The vomiting which is so frequent after chloroform is generally only 
a matter of more or less inconvenience. But in the special case of ovariotomy 
the disturbance of the abdomen thus occasioned is thought to have sometimes 
been the cause of death. Dr. Thomas Keith, whose remarkable success in that 
operation is well known, was led to try sulphuric ether, in the hope that it might 
prove less objectionable in this respect, and the result has been in the highest 
degree satisfactory, so that whereas with chloroform vomiting was the general 
rule, it now seldom occurs in his practice. Dr. Keith has also ascertained 
that if truly anhydrous ether be employed, it can be given so as to produce 
its effect almost as rapidly as chloroform, and without waste of the material, 
by simply pouring a little of the liquid occasionally upon a piece of flannel con- 
tained in a cup-shaped vessel adapted to the mouth and nose, with a small 
aperture for the entrance and exit of air. Hence, as there are various other 
operations in which the avoidance of vomiting is a matter of great moment, 
sulphuric ether seems likely to reassume an important place as an anaesthetic. 
Nitrous oxide, which we had looked upon as of mere historical interest, 
as a kind of pioneer in anaesthesia, has also been revived of late years and turned 
to practical account, chiefly through the exertions of Dr. Evans, an American 
dentist residing in Paris. It is a remarkable fact, that when inhaled unmixed 
with atmospheric air, it fails to produce the excitement to which it owes the 
name of ‘laughing; gas’, but merely throws the patient very rapidly into 
a condition of complete coma, attended with great lividity of the face, and 
staring dilatation of the pupils, presenting a very alarming appearance when 
seen for the first time, but, as experience shows, free from danger, subsiding as 
rapidly as it supervened, and leaving in the great majority of cases no trace of 
sickness or other unpleasant effects. The agent has recently been rendered 
much more portable by keeping it stored in the liquid form in a strong cast-iron 
bottle, from which, by turning a stopcock, the gas is supplied to an india-rubber 
bag, large enough to contain about an average dose for producing insensibility. 
When this is exhausted, the balloon can be refilled in the same way as often as 
may be desired, and thus it is possible by a series of intermitted administrations 


1 See Lancet, August 20, 1870. 


ODF ANAESTHETICS 155 


to keep a patient under the influence of the gas for a protracted period. It is 
questionable, however, whether nitrous oxide, if employed for producing long- 
continued insensibility, would prove as safe as chloroform, and it is pretty 
generally admitted that its legitimate place is for operations of very short dura- 
tion. But for avoiding the brief but acute agony of tooth-extraction it appears 
to be an unquestionable boon to humanity. 

The benumbing influence of cold was brought into requisition several years 
ago by Dr. James Arnott for producing local anaesthesia, by means of a freezing 
mixture of pounded ice and common salt.1_ The same object has since been 
more efficiently attained by Dr. B. W. Richardson, by ingeniously availing 
himself of the reduction of temperature occasioned by evaporation. Anhydrous 
sulphuric ether intimately mingled with air in the form of spray is projected 
upon the part by means of a suitable apparatus easily worked by the hand. 
In a few seconds the skin upon which the spray plays suddenly assumes a snow- 
white colour, implying that its surface is completely frozen. It is well to con- 
tinue the application for a little while after this change has occurred, in order 
to ensure the penetration of the effect to a sufficient depth. The frozen parts 
may then be incised or operated on in any way that may be desirable, without 
the slightest pain to the patient, and the tissues when thawed are generally as 
well disposed for healing as usual. 

This method is necessarily of limited application. It is only adapted for 
superficial operations, and even for many of these the rigidity of the tissues 
occasioned by congelation is inconsistent with efficiency of performance, as in 
removing epithelial cancers, where the sense of touch is the principal guide for 
the surgeon ; or, again, in taking away thin-walled atheromatous cysts, where 
looseness of the surrounding cellular tissue is essential to satisfactory dissection. 
Nevertheless there are many cases, such as the incising of a boil or the removal 
of the nail of the great toe, in which this means of producing local anaesthesia 
proves perfectly satisfactory. In operating on the extremities I have found 
great advantage from restraining the circulation with a tourniquet, so as to 
prevent the oozing of hot blood, which would otherwise interfere with maintain- 
ing the frozen condition or extending it to deeper parts. 


ParT III. WRITTEN 1882 


Since Part II of this article was written, twelve years ago, ether, on account 
of its supposed greater safety, has to a large extent superseded chloroform 
in the practice of many British surgeons. At the same time the manner of 


1 See Lancet, October 30, 1858. 


156 ON ANAESTHETICS 


administering it has undergone a remarkable change. Instead of a free admix- 
ture of atmospheric air, such as is essential to safety in giving chloroform, partial 
asphyxia is systematically combined with the toxic influence of the anaesthetic, 
by making the patient breathe over and over again the same air contained in 
a balloon of caoutchouc, a reservoir of ether being interposed between the 
balloon and a closely fitting mask over the mouth and nares. This may for 
convenience be termed the close method of administering ether, as distinguished 
from all varieties of what we may call the ofen method, in which fresh air is 
admitted with each inspiration. It was introduced by Dr. Ormsby of Dublin, 
and was brought to great perfection by the late Mr. Clover. Various advantages 
are claimed for it. It certainly greatly economizes the ether, and brings the 
patient very rapidly under its influence. It is also said that by utilizing the 
warmth of the expired air, and thus diminishing the great coldness of the in- 
spired air occasioned in the open method by the rapid evaporation of the ether, 
it prevents a chilling of the lungs which sometimes led to serious and even fatal 
after-effects in the form of acute bronchitis or pulmonary oedema or congestion. 
There can be no doubt that this constituted a real danger of the open method. 
A striking example of death taking place unusually rapidly from this cause is 
given in the Lancet of April 1 of the present year (1882) from a report furnished 
by Dr. Parsons, of New York, in whose practice the case occurred. A healthy 
woman, fifty-four years old, had ether given for the reduction of a dislocation of 
the shoulder of five weeks’ standing, the operation lasting twenty-five minutes.’ 
She took the ether well, about 6 fl. ounces being administered. Five minutes after 
reduction was effected she took some water, and about an hour and a half later 
Dr. Parsons left her apparently well. After the lapse of another half-hour, 
however, the house surgeon found her cyanosed ; and in spite of active stimu- 
lating treatment she died in the course of another hour. On post mortem 
examination the organs generally were found healthy, but the lungs were deeply 
congested. No mention is made of the mode of administration, but from 
the quantity of ether used we may infer that it was some form of the open 
method. Such occurrences are not generally published, but they would appear 
to be by no means very uncommon. A case of death from acute bronchitis 
after an operation on the eye for which ether was given by the open method 
was mentioned to me lately by a surgeon in whose practice it occurred, and 
who had no hesitation in attributing the fatal result to the ether. Mr. Hodges, 
of Leicester, writing in the Lancet of July 15, 1882, says: ‘ As regards deaths 
from ether, I make no doubt many occur which are never reported, for the 
simple reason that the death, instead of being instantaneous (as in the case of 


* See Teale, British Medical Journal, March 11, 1882. 


ON ANAESTHETICS 157 


chloroform), occurs some hours later from bronchitis. At any rate, there have 
been two such deaths from ether at the Leicester Infirmary during the last 
nine years, against two from chloroform in the same period. It is scarcely 
necessary to remark that a fatal event brought about in this manner, though 
less appalling, is as much a death from ether as if it occurred on the operating 
table. 

It would not be right, however, to look upon the close method as simply 
the open method deprived more or less of the risks attendant on chilling of the 
lungs. The close method is, as before remarked, a combination of partial 
asphyxia with etherization, and constitutes a new departure in anaesthesia 
which must be judged of independently. 

From experiments which have been performed upon some of the lower 
animals it has been inferred that there is an essential difference between ether 
and chloroform as regards their action upon the heart: that whereas chloro- 
form, after a brief period of stimulation, depresses it, ether for a long time fails 
to produce any lowering influence, or even acts as a persistent cardiac stimulant,! 
and this has been held to afford clear proof of the greater safety of ether. 

There can, however, be no doubt that any agent capable of producing 
anaesthesia must, if continued in operation for a considerable time, exercise 
a lowering effect upon the whole vital powers. Ether, moreover, has its own 
special risks. Its vapour has an irritating effect upon the air-passages, such 
as is not caused by chloroform. Hence it increases the bronchial secretion, 
and tends to produce asphyxial complications, so that even its warmest advo- 
cates do not advise its employment when the respiration is seriously embarrassed, 
as in chronic bronchitis or emphysema. But asphyxia, even when carried to 
a minor degree, has a depressing effect upon the circulation ; and accordingly 
on reading reports of death from ether, we often find it stated that the pulse 
and breathing ceased simultaneously. 

In the close method of administration, anaesthesia being only partly brought 
about by the ether, asphyxial complications due to the action of the ether fer se 
are necessarily less than in the open method. But, on the other hand, the 
partial asphyxia by which the action of the ether is supplemented in the former 
method, has a lowering effect upon the circulation. Hence a stimulating action 
of the ether upon the heart can by no means be reckoned on when this method 
is employed. On the contrary, the pulse may become, within a very short 
time, greatly reduced in force. This is illustrated by the instructions which 
accompany Mr. Clover’s smaller inhaler as supplied by Messrs. Krohne and 


1 See Report of a Committee of the Medico-Chirurgical Society, Med.-Chiy. Trans., vol. xlvii, 
1864, P. 335- 


158 ON ANAESTHETICS 


Sesemann, in which the following sentences will be found: ‘ If any interruption 
in the breathing occur, or 7 the pulse should be indistinct’ (the italics are mine), 
‘the face-piece need only be removed for one inspiration. The dark colour 
of the blood is a less reliable test of the need of air than the symptoms mentioned.’ 
We cannot, therefore, be surprised to find that occasionally death takes place 
under this method of administration by primary failure of the heart. 


In the British Medical Journal for July 15 of the present year Mr. Lawson Tait 
has put upon record what seems a perfectly clear example of such an occurrence. 
The patient, aged forty-five, was sent to Mr. Tait to be operated on for a large 
abdominal tumour. She was at first very anaemic and feeble, but improved 
in the hospital, so that it was decided to proceed to operation. She was placed 
under ether by means of Ormsby’s inhaler, but before complete anaesthesia 
had been produced, Mr. Tait, who was observing the pulse, noticed that it had 
disappeared. Meanwhile ‘ the breathing was perfectly regular and deep’. The 
inhaler was at once removed, but in spite of artificial respiration, with lowering 
of the head, the breathing rapidly failed. ‘ Death took place at the heart at 
least one minute before the respiration was interfered with.’ On post mortem 
examination the right side of the heart was found filled with clot, and the left 
side empty. The muscular substance was not distinctly diseased, but the 
organ was unusually small. 


As a matter of physiological theory, supposing the heart to be diseased, 
and therefore liable to have its rhythmical action suspended by comparatively 
trivial disturbing causes, we could well understand that the unusual labour 
thrown upon the right side of the organ by asphyxial impediment to the pul- 
monary circulation might prove extremely serious, even in spite of a stimulating 
action of the ether upon it. 

With regard to chloroform I fear some of the more recent experiments upon 
the lower animals have had an injurious practical tendency. Since the time 
of Dr. Snow we have understood that there is a most important difference in 
the effects of chloroform according to the proportions in which the vapour is 
mixed with the air inhaled: that when it is present in a concentrated form, 
it acts as a deadly sedative upon the heart, but that when largely diluted 
with the atmosphere, this effect is no longer observed, but if the agent is pushed 
far enough to cause death, the respiration probably fails before the circulation. 

Yet in the experiments conducted by the Committee of the British Medical 
Association appointed to inquire into this subject, the question of the proportion 
of the anaesthetic to the air seems to have been entirely neglected. Starting 
with the assumption that chloroform, from its depressing influence upon the 
heart, is more dangerous than ether, while ether is much less convenient for 
administration, the attention of the Committee was chiefly directed to an en- 
deavour to discover some agent intermediate between them in these respects ; 


ON ANAESTHETICS 159 


and such they found, as they believed, in ethidene dichloride, which they accord- 
ingly recommended as preferable to either of the others. But in order to ascer- 
tain the relative effects of the different substances upon the heart they used 
them all in a very concentrated form, the air being in many of the experiments 
made to bubble through the liquid contained in a Wolfe’s bottle on its way to 
a tube tied into the trachea; so that, to quote the words of the Committee, 
‘the air passed into the animal’s lungs was saturated with the vapour of the 
substance used.’ + Hence these experiments, though very interesting from the 
new facts which they elicited regarding ‘ ethidene’, and valuable as respects 
ether, by showing that it may be safely given, so far as the heart is concerned, 
in a very concentrated form, have really little bearing upon the use of chloroform 
in the human subject, where it is well understood that the agent must be given 
largely diluted with air. 

But these researches, by placing before the profession in an exaggerated 
form the effects of chloroform as a cardiac sedative, have tended to foster the 
idea that if chloroform kills, it always does so from the heart, and that the 
pulse is the main thing to be attended to in its administration. 

Against this pernicious error I have endeavoured in the earlier parts of 
this article to raise an emphatic protest. I have pointed out how liable 
the breathing is to become obstructed under chloroform, whether by the falling 
back of a relaxed tongue or by closure of the valve of mucous membrane which 
guards the orifice of the larynx ; and, further, how obstruction from either of 
these causes may occur without premonitory stertor, in an insidious manner 
requiring the utmost vigilance for its detection; so that, unless the attention 
is fixed upon the respiration, mere heaving of the chest and abdomen (which 
will continue long after air has ceased to enter the lungs), though doing nothing 
for the respiratory function, may be mistaken for effective breathing, the 
patient meanwhile being exposed to the serious dangers which attend a com- 
bination of asphyxia with the effects of chloroform. On the other hand, I have 
contended that if the breathing is carefully observed, and the obstructions 
referred to are removed as soon as they occur, due care being taken to avoid 
pushing the agent beyond what is needful to produce its anaesthetic and relaxing 
effects, the chloroform being given well mixed with the air by means of a folded 
towel held loosely over the face, all fear of primary failure of the heart may be 
dismissed from the mind. 

The experience of the last twelve years has confirmed me in the soundness 
of this doctrine ; and I venture to think it not undeserving of careful considera- 
tion that in my hospital cases I have still entrusted the administration of the 


? See ‘ Report on the Action of Anaesthetics,’ &c., Brit. Med. Journ., December 18, 1880, p. 957. 


160 ON ‘ANAESTHETICS 


chloroform, not to a specialist or to a person of very large experience, but to 
a succession of senior students, changing from month to month, whose only 
qualification for the duty is that they must previously have served the office 
of dresser, and that they strictly carry out certain simple instructions, among 
which is that of never touching the pulse, in order that their attention may not 
be distracted from the respiration. I have also systematically abstained from 
making any preliminary examination of the heart, thus avoiding needless alarm, 
which we know to have been the cause of some fatal events both with chloroform 
and with ether.t. Such has been my practice since IJ first obtained the office 
of full surgeon to a large hospital twenty-one years ago, and I have never had 
reason to regret it. 

During this long period I have often operated upon patients known to be 
affected with disease of the heart, and among the rest there must necessarily 
have been included many affected with fatty degeneration of its muscular 
fibres, which is regarded as the most formidable condition with reference to 
chloroform. 


It happened not long ago that an elderly lady, whose mamma I removed 
for scirrhus, died a few days after the operation from the singular complication 
of perforation of the duodenum by an ulcer caused apparently by the irritation 
of gall-stones. She had taken the chloroform quite well, but I found on post 
mortem examination that the heart was affected with as extreme a degree of 
fatty degeneration and at the same time thinning of the ventricular walls as 
I could well imagine to be consistent with the maintenance of the circulation. 


Such being my own experience, and well knowing how apt the adminis- 
trator is to fail to notice the insidious obstruction of the respiratory passages, 
I cannot help believing that in many of the cases reported in the journals where 
primary failure of the heart is stated to have occurred, mere respiratory move- 
ment without respiratory function has been mistaken for true breathing con- 
tinuing after cessation of the pulse. 

It is, alas! true that I can no longer speak of never having had in my own 
experience a death occasioned by chloroform. One unmistakable instance of 
this fearful calamity occurred lately in my private practice. But the circum- 
stances were such as seem to me to preclude the idea of syncope. They were 
as follows :—- 


A strong, healthy man, twenty-seven years of age, came under my care with 
a lumbar abscess unconnected with the vertebrae. I proposed to open it under 
chloroform, which was administered from a folded towel. The patient struggled 
rather more than usual during the administration, which had not been carried to 


+ For an instance of death from fright at the commencement of the inhalation of ether, see Brit. 
Med, Journ., November 17, 1877; case reported by Dr. Lowe, of Lincoln. 


ON ANAESTHETICS 161 


the degree of producing muscular relaxation when he began to make a spurious 
snoring or snorting noise, which is generally a sure indication that the patient 
requires more chloroform. Mr. Watson Cheyne, who was giving the chloroform 
for me, had, however, removed the cloth from the face, and I was about to 
remark that this was an unnecessary precaution, when the patient fell into 
a sort of epileptiform condition, attended with a state of spasm of the respiratory 
muscles and wide dilatation of the pupils, while the face was deeply livid. As 
no respiratory movements were going on, I had him drawn up on the table 
so as to make the head dependent, and commenced artificial respiration, while 
the tongue was drawn forward with artery forceps. The chest, however, seemed 
fixed in the state of expiration, so that compression of the thorax caused no 
escape of air, while the drawing up of the arms equally failed to cause the en- 
trance of any. I have frequently performed artificial respiration, but never 
before met with such a state of things. Cold water was dashed upon the chest 
and abdomen, and, whether as a consequence of this or not, two spasmodic 
acts of inspiration took place, separated by a considerable interval. I opened 
the trachea, but in the condition of the thoracic walls which I have described, 
this procedure was in itself completely futile. Some little time having been 
lost in vain attempts at artificial respiration, I passed down the trachea from the 
wound a piece of wide india-rubber tubing several inches long, and by blowing 
into this succeeded in inflating the lungs, as was indicated by rising of the 
abdomen and very slight elevation of the ribs, and I continued artificial respiration 
in this way for about half an hour in vain. The pulse had been observed to be 
good just before the occurrence of the alarming symptoms. What its condition 
was during their presence we were too much occupied to ascertain ; but the great 
lividity of the face, and indeed of the whole body, clearly indicated that the heart 
continued to drive imperfectly oxygenated blood through the vessels long after 
the respiration had been arrested by muscular spasm. We obtained permission 
to examine the heart twenty-four hours after death, and found its muscular 
substance abundant and healthy, and its valves all competent. With the 
exception of some spots of slight opacity on the mitral valve, it was a thoroughly 
healthy heart. Its cavities contained fluid blood; and this escaping on the 
removal of the organ from the body, the relative amount in the cavities of the 
two sides was not ascertained. I afterwards learned that the patient had been 
in a state of extreme terror at the prospect of taking chloroform ; and I suspect 
that this may have been the cause that determined the occurrence of the strange 
state of nervous excitement which proved fatal to him. By a curious coin- 
cidence it happened that the medical man who recommended this patient to 
my care, on learning of our disaster, wrote to me stating that a short time pre- 
viously he had met with a very similar state of epileptiform spasm of the 
respiratory muscles in a man in whom he was examining a simple fracture 
without chloroform. It lasted so long that my friend considered that it was 
on the verge of proving fatal. Of course in my case the chloroform was the 
cause of the fatal event, but my impression is that it would have been as likely 
to happen under any other anaesthetic. 


Quite recently the subject of the different effects produced by an anaesthetic, 


according to the proportion which it bears to the air in which it is diffused, has 
LISTER I M 


162 ON ANAESTHETICS 


been brought forward in an exceedingly striking manner by Monsieur Paul Bert. 
Experimenting in a manner essentially similar to that adopted by Dr. Snow, 
diffusing various quantities of the anaesthetic in air contained in a vessel of 
known capacity, so large as to avoid all chance of asphyxial complications, 
he has arrived at remarkable conclusions. So far as I can gather from the 
very brief account which he has published (Comptes Rendus, Nov. 14, 1881), 
he concludes that there is a certain percentage below which chloroform fails 
to produce any anaesthetic effect, however long it continues in operation ; 
that there is another percentage, at or above which it proves mortal (‘]’animal 
finit par mourir’) ; and that between these two definite proportions there is 
a ‘workable zone’ (‘zone maniable’) which produces anaesthesia, but does 
not kill; and when the quantity of chloroform is such as to be about the middle 
of this zone mantable, the animal is rapidly anaesthetized (‘il est tres rapidement 
anesthésié ’), and yet may be safely left for an indefinite time in the same atmos- 
phere (the experiment was sometimes continued as long as two hours), ‘ sans 
qu’on ait a s’occuper ni a s’inquiéter de lui.’ Curiously enough, the smallest 
mortal proportion was just double the smallest anaesthetic quantity ; and this 
held for all kinds of animals, although the absolute amount differed for different 
species. And the same law obtained with ether, bichloride of methylene, and 
other anaesthetics which were made the subjects of experiment. 

These views are so startling that, if it were not for M. Paul Bert’s high 
scientific reputation, we should be disposed to disregard them altogether. There 
can, however, be no doubt of their great importance if correct, and I have 
endeavoured to test their accuracy by some experiments similar to his with one 
of the species which he employed, viz. the mouse, and though my experience 
is very limited, being confined to results obtained from a single family of white 
mice, yet it seems deserving of mention. 


There were four young ones just ready to leave their dam, and I found, 
as Dr. Snow had done, that the young animals of this species were more tolerant 
of chloroform than the adult. The creature was in every case introduced into 
a large glass jar of known capacity, containing air through which a certain 
percentage by weight of chloroform had been thoroughly diffused, assuming 
one hundred cubic inches of air to weigh thirty-one grains, which for practical 
purposes was sufficiently accurate. 

Seven per cent.,? which is the middle of Paul Bert’s zone maniable for the 
mouse, proved much too strong for my animals, causing complete arrest of 
the breathing in one of the young ones in a quarter of an hour, though it recovered 
on being at once withdrawn from the chamber. An adult, the father of the 


' It is to be borne in mind that the percentage by weight is a totally different figure from the per- 
centage by volume used by Dr. Snow and adopted in Part I of this article, the vapour of chloroform 
being 4-2 times heavier than air. 


Re 


ONTANAESTHE TICS 163 


family, was killed by the same percentage in four minutes, and, the chest being 
at once opened, the heart was found to have entirely lost its irritability, failing 
to contract when pricked with a needle. This percentage, then was clearly 
within Paul Bert’s mortal zone for these white mice. Four per cent. (4.9 being 
the extreme lower limit of Paul Bert’s zone maniable for the mouse) caused 
complete anaesthesia in three minutes and a half in another of the young 
animals ; and this atmosphere being continued in operation produced a pro- 
gressively lowering effect upon the breathing, which was reduced in the course 
of one hour and twenty minutes from two hundred per minute to twenty-eight 
shallow and irregular respirations, after which the animal died. The heart was, 
however, found beating when the chest was opened twenty minutes later, and 
the exposed organ continued to pulsate even for another hour, showing how 
little its power had been affected by the chloroform in the more diluted state. 

The experiments being continued on the following day, three per cent. of 
chloroform rendered one of the young animals completely passive in two minutes 
and a half; and within four minutes it had brought the respirations down to 
seventy-eight, and in the course of one hour and three-quarters reduced them 
to about twenty feeble and irregular movements, after which they ceased 
entirely, and did not recur, although the animal was withdrawn from the cham- 
ber within two minutes and a half of their cessation. The more rapid anaes- 
thesia and greater depression of the respiration occasioned by this smaller 
percentage of chloroform are, I believe, to be explained by a feeble state of the 
animal, caused by its having been the subject of the first experiment on the 
previous day. The fact illustrates the different susceptibilities to chloroform 
that may be presented by the same individual under different circumstances. 

Two per cent., tried with another of the young mice, made the animal 
stagger in about two minutes, but failed to produce complete anaesthesia in 
an hour ; and at that time the respirations continued as high as one hundred and 
sixty per minute. But after the lapse of another hour anaesthesia was found 
to be complete, and the respirations reduced to eighty-six. In the course of 
two hours more the breathing was further lowered to fifty-six, and it was evident 
that death would occur in no long time if the animal were kept in the same 
atmosphere. It was removed, and recovery took place, but only very slowly, 
no movement of the limbs showing itself for nearly an hour. 

Lastly, a percentage intermediate between those of the last two experiments 
was tried, viz. two and a half. It produced anaesthesia somewhat slowly in 
the young animal subjected to it, requiring a quarter of an hour for complete 
relaxation. The respirations meanwhile had come down from about two hundred 
to one hundred and sixty-eight, and, after the lapse of twenty-two minutes more, 
had fallen to one hundred and four. The animal was now left unobserved in 
the chamber for another hour, and at the end of that time it was found dead. 
It will be observed that two and a half per cent., though it anaesthetized more 
slowly, yet killed sooner than four per cent. had done on the previous day. 
The subject of the experiment had, I fear, been weakened by being kept in 
less favourable hygienic conditions since it was got from the dealer the day before. 


The facts elicited by these experiments, though not numerous, seem to me 
instructive. In the first place, they afford an illustration of Dr. Snow’s impor- 
M 2 


164 ON ANAESTHETICS 


tant principle, that there are two essentially different ways in which chloroform 
may kill, viz. by a directly sedative action on the heart when the chloroform is 
in large proportion to the air, and by a suspension of the respiratory function, 
while the heart is still acting, when the chloroform is largely diluted. They 
also show how different individuals of the same species, and even the same 
individual at different times, may differ in susceptibility to chloroform. And 
in the third place they indicate, I fear, but too plainly, that we cannot by any 
means trust implicitly to the existence of Paul Bert’s three distinct zones. For 
we have seen that a proportion of chloroform which produced anaesthesia so 
extremely slowly that, if 1t was within the anaesthesic zone at all, it must have 
been at its very lowest limit, nevertheless exerted a gradually increasing dele- 
terious influence, tending at last to a fatal result. And when the proportion 
was increased so as to make any approach to the ‘ very rapid’ anaesthetizing 
effect which, as M. Bert tells us, characterizes the middle of the zone maniable, 
a similar but more rapid deleterious action was observed, causing death con- 
siderably within the two hours referred to by M. Bert. We see, therefore, that, 
for those animals at least, there existed no efficiently anaesthetic mixture of 
chloroform and air, which could safely be left in continuous action for such 
a length of time as is not unfrequently occupied by a surgical operation. 
Hence, whether we regard the various degrees of susceptibility to chloro- 
form shown by different individuals, or the sure though gradual lethal effects 
of even the smallest proportion which suffices to be anaesthetic, I fear the pro- 
posal which I understand M. Bert to make, that the zone manzable having been 
ascertained for man, a corresponding atmosphere should be provided in a large 
reservoir, from which the patient should be allowed to inspire continuously 
throughout the duration of an operation, must be rejected as highly dangerous. 
But, although I have thus failed to verify M. Paul Bert’s precise conclusions, 
yet I believe we owe him a deep debt of gratitude for his researches. The 
experiments which I have conducted on the lines which he has laid down have 
made manifest an important truth entirely new to me. I had always supposed 
that a chloroform atmosphere sufficiently strong to produce anaesthesia would, 
if continued, soon lead to a fatal result. Such certainly is apt to be the case 
with chloroform administered by means of a folded towel. It once fell to my 
lot to see a patient who had been left for only a few minutes with the cloth 
lying over the face after full anaesthesia had been produced, in consequence 
of the attention of the administrator having been distracted by other matters, 
and I shall never forget the result. Respiratory movements had entirely ceased, 
and the face had a deadly pallor, and for a while it appeared as if the patient 
was dead, though happily revival took place after protracted artificial respiration. 


ONPANAESTHESLICS 165 


And I have seen other patients thrown into a condition of distinct peril from 
the same cause carried to a minor degree. Yet we have seen in the experiments 
above recorded that, even in animals which seem to have been peculiarly sensi- 
tive to the action of chloroform, atmospheres which produced anaesthesia in 
a very few minutes did not cause death till they had continued in action con- 
siderably more than an hour. Those atmospheres had the peculiarity of being 
on the one hand, extremely mild, and, on the other hand, constant in quality . 
and, assuming that effects more or less closely analogous would follow in the 
human subject, it is clear that we ought to make a systematic attempt to attain 
them. If for the fitful mode of administration by the folded towel, with atmos- 
pheres perpetually oscillating between the needlessly strong and the uselessly 
weak, we can substitute a method which shall give a uniform and at the same 
time a mild anaesthetic air, we may anticipate very beneficial results. The 
avoidance of the needlessly strong atmospheres can hardly fail to diminish the 
chances of mishap from inadvertence, and this in two ways: first, by making 
respiratory embarrassments less likely to occur; and, secondly, by rendering 
it far less dangerous to continue the administration of the anaesthetic when 
the patient is fully under its influence. An equable exhibition of the drug 
will also save time, and thus not only promote the convenience of the surgeon, 
but also the comfort of the patient, since the after-effects of the narcotic are 
more or less proportioned to the length of the period during which it has con- 
tinued in operation. 

Moreover, the facts which M. Paul Bert has elicited may well embolden 
us to continue a steady administration of the chloroform after the patient has 
been brought fully under its influence. For we know that, when complete 
anaesthesia has been brought about, a very much smaller proportion of the 
chloroform is needed for the maintenance of that state than was required for 
its production: all that is necessary being to supply enough to compensate 
for the elimination of the drug by the lungs and other emunctory organs. Hence, 
if an atmosphere of the mild but constant character referred to, while effective 
for the rapid production of anaesthesia, may in the lower animals be continued 
for an hour or more of full strength without causing death, it seems only reason- 
able to anticipate that, if the greatly reduced proportion that suffices for main- 
taining anaesthesia were substituted when the patient had been fully subdued, 
it might be steadily continued without danger for any length of time that might 
be desirable. And I need hardly remark on the convenience that would result 
from such an arrangement, as compared with the liability to partial recovery 
with its attendant struggling in the middle of an operation, when chloroform is 
given from the folded towel by any but very experienced administrators. 


166 ON ANAESTHETICS 


But there is reason to believe that other important advantages will be 
gained by more uniform administration. It would appear that there are serious 
objections to allowing the patient to recover from time to time from the effects 
of the chloroform. Dr. Kirk of Glasgow made, several years ago, some inter- 
esting observations bearing on this subject, which have not yet been published, 
but which he kindly allows me to refer to. He found that if a cat was placed 
in a jar containing an anaesthetic mixture of chloroform with air, and removed 
when it was only partially anaesthetized, and at once examined with the stetho- 
scope, the pulse always made a sudden and considerable rise from the depression 
which the chloroform occasioned, and not unfrequently this rise was followed 
by a complete suspension of audible cardiac pulsations, lasting it might be for 
an entire minute. If, however, the animal was retained in the jar till complete 
anaesthesia was effected, such suspension of pulsation was never observed. 
I am not aware that anything exactly corresponding has been observed in the 
human subject. But I have often seen great pallor precede vomiting under 
chloroform, and it seems probable that this vomiting, and the depression 
which accompanies it, have been due to the fitful way in which we have been 
in the habit of giving chloroform with the folded towel. For Dr. Kirk, who 
has paid great attention to this subject, informs me that he has never seen 
vomiting occur under chloroform except during recovery from the anaesthesia. 
And this experience is strikingly confirmed by Mr. Meredith, of the Samaritan 
Hospital, who tells me that he avoids vomiting during ovariotomy by giving 
chloroform with Junker’s inhaler, in which air is driven by Richardson’s hand- 
bellows through a bottle of the liquid, and thence into a vulcanite mask over 
the mouth and nose, where it mixes freely with pure atmospheric air inhaled 
through a valve in the mask. In this way the chloroform is given in a mild 
and very uniform manner till the patient is fully anaesthetized, and afterwards 
any approach to recovery is anticipated by the occasional use of the bellows. 
And not only is vomiting prevented during the operation, but the further highly 
satisfactory result is obtained that the patient is not affected to any material 
extent with the after-sickness which formerly proved so serious in ovariotomy, 
and induced Dr. Keith to abandon chloroform in favour of ether. 

Vomiting under anaesthesia is a serious matter, requiring prompt attention 
in the way of turning the head well to one side, in order to avoid the risk of 
vomited matter passing into the larynx. Ether seems more liable to cause 
vomiting during actual anaesthesia than chloroform, and several of the deaths 
under ether which have been published have been from this cause. But after- 
sickness appears to be much more frequent and more distressing with chloroform 
administered by means of a folded towel than with ether ; and it will be a great 


= =o —————— 


ON ANAESTHETICS 167 


point gained if this serious drawback, together with the depression that attends 
it, can be got rid of. 

Junker’s inhaler acts admirably in experienced hands, but the working 
of the bellows is a somewhat irksome business ; and there is, besides, the great 
disadvantage of a special apparatus which may not be always at hand, and 
which, if not in frequent use, is liable to get out of order. And I cannot but 
think that, if the valve of the mask is not properly managed, there will be danger 
of the chloroform being given in too concentrated a form. 

A much more simple way of giving chloroform in a continuous and equable 
manner is that of dropping it frequently, by means of a drop-bottle, upon a 
flannel bag stretched over a wire frame, as was, I believe, first suggested by 
the late Dr. Skinner, of Liverpool. The drop-bottle may be very simply made 
by providing an ordinary bottle with a second cork traversed by a piece of glass 
tube sufficiently small in calibre to allow only one or two minims to escape at 
once when the bottle is momentarily inverted. Special drop-bottles of more 
durable and convenient construction may be got from the instrument-makers ; 
but for an emergency a cork, with a small notch cut out of one side, introduced 
into a common bottle, will answer the purpose sufficiently well. By these 
means chloroform may be given in a very steady, continuous manner; and 
some who are accustomed to this method speak very highly in its favour. But 
Dr. Skinner’s bag is needlessly large; and from this circumstance, and also 
from the very accurate manner in which it applies itself to the face by means 
of an elastic band at its orifice, it must be apt, unless cautiously used, to accumu- 
late too large a quantity of chloroform ; and I know that deaths have occurred 
under its use. 

A much smaller frame is also sold by the instrument-makers, with a corre- 
spondingly smaller flannel bag, fitting, like Skinner’s, accurately to the face. 
This apparatus proved on trial amply adequate, anaesthesia being very rapidly 
induced, with extremely little consumption of chloroform. But, even though 
so much smaller, the closely fitting bag seemed to me liable to the danger of 
giving the chloroform too strong, especially when the breathing is shallow. 
I therefore made trials with a piece of flannel stretched over the small frame, 
but having an interval of about half an inch between its border and the sk'n 
of the face ; and I found that a piece with an area of nine square inches arranged 
in this way, and kept constantly moist with chloroform, failed to induce anaes- 
thesia within a reasonable time in an adult male, but answered the purpose 
well if a piece of rag was thrown lightly round the interval between the flannel 
and the skin, so as to check, but not altogether prevent, the flowing away of 
the heavy vapour of the chloroform. Thus I seemed to have arrived at an 


168 ON ANAESTHETICS 


arrangement as near the lower limit of efficiency as was possible. And as there 
is no special virtue in flannel, as compared with a single layer of linen of coarse 
texture, I substituted for the frame and flannel the corner of a towel, pursed up 
systematically into a concave mask to cover the mouth and nose by pinching 
it together at such a distance from the corner that, when the pinched-up part 
is held over the root of the nose, the corner extends freely to the point of the chin. 

The cap formed in this manner being so arranged upon the face, chloroform 
is gradually dropped upon it till the greater part of it is soaked, the edges being 
left dry to avoid irritation of the skin by the liquid; and the moist condition 
is maintained by frequent dropping until the requisite physiological effects are 
produced ; the respiration being at the same time carefully watched with a view 
to the instant adoption of the measures described at p. 144 in case of any 
obstruction to the free entrance of air. When full anaesthesia has been pro- 
duced, it is steadily maintained by dropping with about half the frequency : 
for I find that half the quantity of chloroform per minute that is used for pro- 
ducing anaesthesia is not far from the amount required for maintaining it. 
Any one accustomed to giving chloroform with the folded towel or compress 
has to learn to avoid the two extremes of applying the drop-bottle too seldom, 
and putting on too much chloroform at a time. 

In giving chloroform in this manner, it is of great importance to bear in 
mind that the amount inhaled is proportioned to the surface which is moistened, 
so that it would not be right to use an indefinitely large piece of towel for the 
purpose. When the cap is made as above directed, large enough to extend 
freely from the root of the nose to the point of the chin, the part which is mois- 
tened during the production of anaesthesia has an area of about nine square 
inches (that of a circle three and a half inches in diameter) in the case of the 
adult male. But the apparatus is self-adjusting in so far that the cap varies 
in dimensions with the face, which, again, is more or less proportioned to the 
size of the body; and thus, for example, a very much smaller evaporating 
surface is provided for a young child than for an adult. It is further self-regu- 
lating in this respect, that when the breathing is shallow, and the quantity 
of air to be mixed with the chloroform consequently diminished, the percentage 
of the chloroform is not correspondingly increased, because a much smaller 
amount evaporates under those circumstances than when the air is moved 
freely over the cloth in deep inspiration ; and further, when the vapour is not 
drawn into the chest, its density causes it to flow away under the loose margins 
of the cap, instead of accumulating as it would do under a closely fitting bag. 

When the surface of the towel is restricted as above recommended, the 
proportion of chloroform to the air inhaled is extremely small. In order to 


ON ANAESTHETICS 169 


estimate this proportion, it is necessary to ascertain, on the one hand, how 
much chloroform enters the lungs per minute, and, on the other hand, how 
much air is inhaled during the same period. The former element is obtained 
as follows:—The drop-bottle being graduated, the quantity of chloroform 
employed for the production of full anaesthesia is determined by inspection, 
and the number of minutes which have elapsed during the process is also noted. 
The amount of chloroform which is known to be necessary to moisten the cap 
being subtracted from the whole employed gives the quantity which has evapor- 
ated from both surfaces during the time of administration; and this divided 
by the number of minutes gives the total evaporation per minute. Then, 
allowing with Michael Foster that inspiration occupies about four-elevenths of 
the whole respiratory period, this fraction of the total evaporation per minute is 
that which was given off from both sides of the cap per minute during inspiration. 
But this does not all really enter the lungs: a certain quantity of the heavy 
vapour, particularly of that which comes from the upper surface, falls away 
unconsumed, and this loss cannot be considered less on the average than a third 
of the quantity given off from both surfaces during inspiration, so that two- 
thirds of that amount is approximately the quantity of chloroform inhaled per 
minute. In order to form an estimate of the quantity of air with which this 
chloroform is mixed, I have carefully ascertained, by simple means which I need 
not here describe, the number of cubic inches expired per minute by myself 
and also by a healthy woman of about the average stature, both during tranquil 
breathing in the recumbent posture and during the shallowest respiration which 
it was possible to maintain for a minute together, so shallow, indeed, as to 
produce serious discomfort from the besoin de respirer. I also tried in my own 
case the product of full breathing. The results were as follows :— 


For myself. 


Deep respiration gave. . 1350 cubic inches per minute. 
Tranquil respiration gave . 540 3 7 
Shallowest possible respiration gave 200 Z - 


For woman of about average stature. 


Tranquil respiration gave... 360 cubic inches per minute. 
Shallowest respiration gave. ; 235 ” 


From these figures we can form a fair estimate of the amount of air taken 
into the lungs per minute in any given case of administration ; and allowing 
31 grs. for every 100 cubic inches, we calculate the percentage by weight of 
the chloroform to the inspired air, bearing in mind, of course, the relation of 


170 ON ANAESTHETICS 


the specific gravity of chloroform to the fluid measure employed. To take two 
illustrations from actual practice :—A tall, middle-aged man of pretty stout 
build was brought into a state of full anaesthesia in 4 minutes by means of 
1% fl. drachms of chloroform, or 138 grs.; 25 grs. would be about the quantity 
of chloroform remaining on a cap of the size used in his case, and if we allow 
450 cubic inches as the amount of air breathed per minute—and this is a mode- 
rate estimate—a calculation made as above indicated gives 4-9 as the percentage 
of chloroform by weight in the inspired air, or 1-17 by volume. Again, a woman, 
below the average stature and slightly built, was completely anaesthetized in 
44 minutes by means of 1} fl. drachms of chloroform, or 104 grs.: and supposing 
that 15 grs. remained on the considerably smaller cap used in her case, and 
that she breathed 300 cubic inches per minute, we obtain 5-2 as the percentage 
of the chloroform by weight, or 1-2 by volume. The mildness of these atmo- 
spheres will be apparent when I state that M. Paul Bert’s zone mamiable was, 
for the dog, from 7-3 to 15-3 per cent. by weight, or 1-7 to 3-5 by volume, and 
for the mouse, from 4:9 to 9-8 by weight, or 1-2 to 2:33 by volume, so that the 
atmospheres used in the two cases referred to were considerably below the zone 
mantable for the dog and only just at the lower limit of that for the mouse. 
Or the point will perhaps appear still more strikingly when it is borne in mind 
that 5 per cent. by volume was that which Dr. Snow employed with his inhaler, 
and 34 per cent. by volume that which was recommended as the average atmo- 
sphere by the chloroform committee of the Medico-Chirurgical Society... Even 
in the case of extremely shallow breathing, an atmosphere as strong as that 
recommended by the committee would probably never be reached by this method. 
Persons less amenable to chloroform than the average yield to these mild atmo- 
spheres if they are longer continued. Thus a lady who had often taken chloroform 
from the folded towel or compress, and had been with some difficulty brought 
under its influence, was subdued in the course of 7 minutes by means of 23 fl. 
drachms, or 207-5 grs., of chloroform. She was rather a large woman, and 
allowing that 20 grs. were required for moistening the towel, and that she 
breathed 400 cubic inches of air per minute, we find by calculation that the 
percentage of chloroform which she inhaled was 5-3 by weight, or 1-26 by volume. 
On another occasion, a somewhat larger cap being employed, she was anaes- 
thetized in 4 minutes with 2 fl. drachms, or 166 grs., of chloroform, giving a per- 
centage of 6-4 by weight, or 1-5 by volume. These are samples of several ad- 
ministrations in her case, and I observed that when the milder atmospheres 
were used she was free from the short fit of laboured and spasmodic breathing 
which invariably occurred when the larger cap with its stronger atmosphere 


* Vide Med.-Chir. Trans., vol. xlvii, p. 353. 


————$_——— 


ON ANAESTHETICS 71 


was employed. This may have been a mere coincidence, but it seemed to 
indicate that the milder atmosphere, though more tedious in operation, was 
the safer. But in cases which must be expected from time to time to arise, 
in which the system is unusually tolerant of chloroform, when several minutes 
have passed without any apparent effect being produced, there can be no 
objection to making the cap somewhat larger, provided the administrator bears 
distinctly in mind that he increases the strength of the chloroform atmosphere 
in proportion as he enlarges the cap. 

To return for a moment to the last case mentioned, I have to add that, 
although she required more chloroform than the average of patients for the 
production of anaesthesia, yet when this had been effected, it was maintained 
by the steady use of a comparatively small amount. Thus on one occasion 
she was kept perfectly tranquil for 12 minutes during what would have been 
very painful procedures by the use of 2? fl. drachms of chloroform, giving a per- 
centage of 3-75 by weight or -89 by volume, which is certainly an exceedingly 
mild atmosphere. 

This method is a little more troublesome than our old plan of holding a 
folded towel over the face, and replenishing it with chloroform at considerable 
intervals; but the constant attention which it necessitates is an additional 
element of safety. During the last five months I have proceeded on these 
principles, and I have been much pleased with the results. The gradual manner 
in which the chloroform is applied in the first instance makes the administration 
extremely comfortable to the patient ; respiratory obstruction has been markedly 
less frequent than formerly, even the falling back of a relaxed tongue being of 
rare occurrence ; there has been, as a rule, remarkable immunity from vomiting 
or after-sickness, and, except in one instance, no serious depression. 

This exceptional instance deserves detailed mention on account of the 
illustration which it affords of an important point in the preliminary manage- 
ment of the patient. I operated on a delicate boy, twelve years of age, on 
account of the dislocation of the upper end of the radius forwards of many 
years’ standing, removing the head of the bone and returning what remained 
to its natural position, an operation of short duration, and attended with scarcely 
any haemorrhage. Splints having been applied to keep the bone in position, 
the chloroform was discontinued, when some tendency to vomiting showed 
itself. While in this condition he was lifted into bed, and immediately on this 
being done he fell into a state of collapse, which was for a short time sufficiently 
alarming. The explanation of this most unusual occurrence appeared to be 
afforded by the neglect of my orders that he should sleep the previous night at 
the house where the operation was to be performed at nine a.m., and have a cup 


172 ON ANAESTHETICS 


of tea, without bread, at seven o’clock to stay the stomach ; a practice which 
I have for many years adopted. It was only after the operation that I was 
informed that he had taken nothing whatever since five o’clock the previous 
afternoon, and that he had only been brought that morning to the house after 
a pretty long journey through London. This exertion, with prolonged fasting, 
combined with his weakly condition, sufficiently accounted for the symptoms 
of depression. While it is desirable that there should be no solid matter in the 
stomach when chloroform is administered, it will be found very salutary to 
give a cup of tea or beef-tea about two hours previously. 

If chloroform carefully given in the simple manner above recommended is 
really as safe a means of producing prolonged anaesthesia as we possess, a con- 
viction that such is the case will be a great relief to the majority of our practi- 
tioners throughout the country ; all special apparatus being avoided, and selec- 
tion of cases needless. For chloroform, if we are once satisfied of its safety, 
has the grand advantage that it may be used alike for the infant and the aged, 
and for those affected with pulmonary, cardiac, or renal disease. Wherever an 
anaesthetic is demanded, chloroform is applicable. 

For the treatment of alarming symptoms of collapse, whether due to idiosyn- 
crasy in the patient or to want of due watchfulness in the administrator, the 
practice suggested by Nélaton has proved of the greatest value. It is sometimes 
spoken of as ‘inversion’ ; but all that is essential is to place the head at a con- 
siderably lower level than the body generally. Of the practical efficacy of this 
treatment no doubt will be entertained if we bear in mind the relief afforded 
in faintness by placing the patient in a horizontal position, or, if he be sitting, 
by depressing the head to the level of the knees; or, again, the converse fact 
of the occurrence of syncope on a patient sitting up for the first time after a long 
and weakening illness. On mere hydraulic principles, indeed, the beneficial 
effect of inversion would be inexplicable ; seeing that gravity, being equally 
balanced in the arteries and veins, cannot of itself promote the flow through 
the blood-vessels, except in so far as the increased pressure due to that cause 
might lead to their distension and so to diminution of friction; while in the 
special case of the brain the enlargement of the vessels as a whole would be 
effectually prevented by the circumstance of the organ being enclosed in an 
unyielding box. But we know, from observations which I have published 
elsewhere,’ that when any part of the body is raised, its arteries, large and small, 
are thrown into a state of contraction through the vaso-motor nervous system ; 
and conversely, when a part is placed low, its arteries become freely relaxed 


* See an address on the Influence of Position on the Local Circulation, Brit. Med. Journ., June 21, 
1879, reprinted at p. 176 of this volume. 


ON ANAESTHETICS 173 


through the intervention of the same nervous agency, out of all proportion 
to any effect which the increased pressure of the blood upon their walls through 
gravity could occasion. We therefore understand how ‘anaemia of the brain’, 
or languid flow through constricted arteries, may be caused by unwonted eleva- 
tion of the head, and how relaxation of the cerebral arteries, and correspond- 
ingly free flow of blood through them, may be induced by placing the head 
unusually low. 

I have myself seen some striking examples of the advantage of acting on 
Nélaton’s suggestion. 

I once operated for fissure of the anus on a lady above middle life, who 
was so exceedingly liable to fainting fits that two medical friends of hers who 
were present had great dread of her taking chloroform. For my part, I believed 
that if she was to be operated on at all, chloroform would prove advantageous 
by protecting her heart from shock. It was accordingly administered, and she 
took it perfectly well; but before she was fully under its influence I yielded to 
the entreaties of my colleagues, and against my own judgement proceeded to 
the operation. As the knife passed through the sensitive part she ceased to 
breathe, and became deadly pale. I instantly turned her round across the bed, 
so that her head and shoulders hung over its side, and performed artificial respira- 
tion by Sylvester’s method. In a short time natural breathing recurred ; and 
when it had continued for a while, I replaced her in the horizontal position. 
No sooner was this done than the alarming symptoms returned ; but they were 
again dispelled by a repetition of the same treatment. This time I took care 
to keep the head dependent for a considerably longer period, and the result 
was permanent recovery. In that case my belief was that a more complete 
action of the chloroform would have obviated the collapse. 

In another case no such explanation of the syncope was possible. 

I had performed a trifling operation upon the arm of a delicate little girl 
under chloroform in King’s College Hospital. Nothing unusual had occurred, 
and she was sent off on a wheeled couch to the ward, about thirty yards distant. 
Whether she was made to sit up as she was lifted into bed (a thing which 
ought never to be done) I do not know; but she had hardly been placed 
there when she fell into a state of collapse, and I was at once summoned. 
Running to the ward, I found her face blanched, and respiratory movements 
entirely absent. I immediately did as in the former case. No sooner was 
her head placed dependent than a rosy colour suffused the white cheeks ; 
and after a short time of artificial respiration by Sylvester’s method, she was 
breathing naturally. 

I have had occasion to refer more than once to Sylvester’s method of arti- 


174 ON ANAESTHETICS 


ficial respiration. In it inspiration is effected by drawing up the arms above 
the head till they are in a line with the trunk, and thus raising the ribs through 
the medium of the muscles which connect them with the upper extremities ; 
while expiration is produced by lowering the arms and pressing the elbows 
firmly against the front and sides of the chest. I can testify to the great 
superiority of this method over the old plan of merely compressing the thorax 
intermittingly, and trusting to its expansile elasticity for inspiration. 

Inhalation of the vapour of a few drops of nitrite of amyl as a cardiac 
stimulant is stated to have proved useful in some cases of collapse under chloro- 
form. And in accordance with the exaggerated idea of the sedative influence 
of chloroform upon the heart to which I have above referred, the admixture 
of a small quantity of the nitrite of amyl with it has been suggested as a pre- 
ventive of cardiac depression. The proposal has not, however, met with accep- 
tance ; nor is it likely to do so, seeing that the nitrite, while a very potent agent, 
seems to be inconstant in its operation. 

The same dread of the depressing effect of chloroform upon the heart has 
led some surgeons to use it mixed with ether, together with some alcohol to 
produce complete blending of the two liquids. Deaths have, however, occurred 
under the use of such mixtures, and we have no evidence that they are really 
safer than undiluted chloroform carefully given. 

The hypodermic injection of morphia a short time before chloroform is 
administered has been recommended in Germany for some special operations, 
on account of the remarkable result, which certainly follows such practice, that 
the patient may be deprived of sensibility to pain, though still retaining con- 
sciousness and voluntary motion ; so that he is able to assist the surgeon by 
his own exertions. I understand, however, that a very serious depressing 
influence upon the nervous system has been sometimes found to result from this 
combination of the two narcotics. 

A favourite method with some London practitioners is to begin by giving 
nitrous oxide, and when anaesthesia has been rapidly produced in this way, 
maintain it by means of ether. The patient is thus saved the discomfort of the 
inhalation of ether, and I am not aware that any disadvantage attends the 
preliminary use of the nitrous oxide, except the inconvenience of the necessary 
apparatus, which practically must restrict this mode of procedure to dentists 
and persons who devote themselves specially to the administration of anaes- 
thetics. 

Ethidene dichloride, or ethidene, as it is often called for the sake of brevity, 
was recommended, as we have seen, by the Committee of the British Medical 
Association. It happens, however, that in the trials which it has received on 


ON TANAESTHE TICS 175 


the human subject, fatal results have been proportionally more frequent than 
with chloroform. 

Bichloride of methylene, administered by means of Junker’s inhaler, has 
proved itself an excellent anaesthetic. We have, however, no proof of its 
superiority over chloroform, either in safety of administration or immunity 
from subsequent inconvenience. And it has the disadvantage compared with 
chloroform, that it is an unstable compound when kept in contact with the air. 


EFFECTS OF THE POSITION OF A PART ON’) Tie 
CIRCULATION "THROUGH TT 


Read before the Harveian Society of London.’ 


[British Medical Journal, 1879, vol. i, p. 923.] 


Mr. PRESIDENT AND GENTLEMEN.—Having been honoured by a request from 
the Council that I would make some communication to this Society, I have 
thought that no subject could be more appropriately brought before an asso- 
ciation connected with the name of Harvey than some observations begun 
several years ago, but hitherto unpublished, regarding the effects of the position of 
a part upon the circulation through it. 

My attention was first directed to this subject fifteen years since, when 
I was engaged in endeavouring to devise a satisfactory method of excising the 
entire articular apparatus of the wrist for the cure of carious disease. In that 
operation, although no large arterial branches are divided, the very protracted 
character of the procedure would render the oozing from small vessels a source 
of serious loss of blood to the patient if it were allowed to go on unchecked. 
Accordingly, I was led to deviate from what was then the ordinary practice 
of restricting the use of the tourniquet to amputation, and employed the instru- 
ment in the excision referred to. And I found that, when the hand was raised 
to the utmost degree, and kept so for a few minutes, and then, while the elevated 
position was still maintained, a common tourniquet was applied to the arm, 
being screwed up as rapidly as possible, so as to arrest all circulation in the limb 
and at the same time avoid venous turgescence, I had a practically bloodless 
part to operate upon, and thus gained the double advantage of avoiding haemor- 
rhage and inspecting precisely the parts with which I was dealing. And, having 
found such great benefit from this bloodless method of operating in the instance 
referred to, I extended it to other operations on the limbs. 

In 1873, I was one day illustrating this subject to my clinical class in 
Edinburgh by raising one of my hands to the utmost while the other was kept 
dependent, in order to exhibit the contrast between them in redness, when 
a sensation of chilliness coming on in the hand that was raised made me feel, 
and at once express, the conviction that something more was occurring than 


* The paper, as now published, embraces some considerations on which I did not enter at the time 
of its delivery, and also some facts subsequently ascertained. 


EPFECIS OF THE POSITION OF A PART £77 


could be explained by the mere mechanical effect of the position of the part 
upon the blood in the vessels, and that the diminution of pressure upon their 
walls resulting from the action of gravity upon their contained blood must 
operate as a stimulus to the vaso-motor nervous apparatus of the limb, so as 
to induce reflex contraction of its arteries. 

I will now ask this man (with his arms bare) to raise one hand high into the 
air, while the other hangs beside him. You observe at once the striking contrast 
between the two. In the one elevated, not only have the veins entirely collapsed, 
but the colour is almost that of the limb of a corpse. So white is the hand as 
to imply that the minute arteries must surely be in the same state of extreme 
constriction as occurs during syncope. 

I will now apply to the arm close to the axilla a bandage of elastic webbing, 
putting on the first few turns with firmness and rapidity, so as to avoid any 
intermediate condition of engorgement through obstruction of the return by the 
veins before the arteries are completely compressed ; while the later turns may 
be put on, if we please, more leisurely and with less firmness, to ensure, by the 
accumulation of the elastic force, complete maintenance of such constriction 
of the limb as prevents all circulation. The elastic band having been fixed with 
a pin, the limb is lowered and the man will stand aside for a few minutes. 

I may state that, when Esmarch published his method of bloodless operating 
—consisting, as my hearers are all aware, of first expelling the blood from the limb 
by means of an elastic bandage wound firmly round it from the distal extremity 
upwards, and then applying another elastic constricting band in the manner 
you have witnessed just above the first, so as to prevent recurrence of circulation 
on the removal of the latter—I thankfully adopted the use of the upper con- 
stricting band in preference to the common tourniquet. I did so because the 
elastic band has the great superiority over the inelastic strap of the tourniquet, 
that it follows up any yielding that may occur in the soft parts subsequently 
to its application, and thus prevents the necessity which we often used to find 
with the common tourniquet, especially if the limb was swollen through inflam- 
matory or oedematous effusion, of tightening up the instrument repeatedly in 
consequence of recurrence of bleeding, attended on each occasion with venous 
engorgement. But, while I gratefully accepted this part of Professor Esmarch’s 
procedure, I did not see sufficient reason for substituting his mode of emptying 
the limb of blood by elastic bandaging for our former practice of trusting to the 
elevated position. I shall recur to this point in the sequel. 

Being desirous of testing with greater precision than was possible upon the 
human subject the correctness of the view which I had been led to entertain 
of the cause of the paleness of an elevated limb, I performed on November 29, 


LISTER I N 


178 EFFECTS OF THE POSITION OF A’ PART 


1873, the following experiment upon a horse. An arrangement. having been 
made by means of ropes and pulleys, one rope being connected with a broad 
sling beneath the abdomen and others with the feet, so that the animal could 
be either raised into the air with the feet dependent, or laid on its side on the 
ground with the legs extended horizontally, or again placed on its back with the 
feet drawn vertically upwards, chloroform being administered, I exposed, at the 
lower part of one of the fore-legs, an artery about as large as the human vertebral, 
situated along the outer aspect of the metacarpal bone. 

In the elevated position of the limb, the wound proved almost absolutely 
bloodless, closely resembling one in a dead animal ; and the artery was straight 
and pallid, and no pulsation could be perceived in it. When the animal was 
turned round so that the feet were dependent, the artery became much increased 
in size, tortuous, red, and pulsating powerfully, and blood oozed freely from 
the surface of the wound; and when the limbs were placed horizontally, an 
intermediate condition took place, both as regards the artery and the haemorrhage. 
By means of suitable callipers, careful measurements were taken repeatedly 
of the external diameter of the vessel in the different positions of the animal, 
which, having had no chloroform administered after the conclusion of the cutting 
operation, appeared to be in a normal state as regards the force of the circulation. 
The accompanying diagram exhibits the results obtained, and also the section 
of the artery after removal from the body, when it was found contracted to 
almost complete obliteration of calibre. 

You observe that, in the elevated position of the limb, the vessel was nearly 
as small as it was in the state of extreme constriction. On the other hand, 
in the horizontal, and still more in the dependent posture, the external diameter 
became considerably increased. But, in order to judge of the augmentation 
of the capacity of the tube for transmitting the blood, we must look to the area 
of the internal calibre, which, having measured the thickness of the wall of the 
artery after removal from the body, we have the means of estimating for the 
various positions of the limb. For, the substance composing the arterial wall 
being of course a constant quantity, the ring constituted by its transverse section 
has always the same area, though varying in form, being thinned out as the vessel 
expands. The area of the ring is calculated from the dimensions obtained 
after removal of the artery from the body, viz. the external diameter and the 
thickness of the wall ; and the area of the internal calibre for any other condition 
of external diameter is simply the area of the corresponding circle minus the area 
of the ring. The numbers in the diagram are hundredths of an inch, and the 


" In truth, the increase of internal calibre in the dependent position is thus rather underestimated 
because the tortuous form which the vessel then assumed implied a certain amount of increase in its 


ON THE CIRCULATION’ THROUGH IT 179 


drawings are accurate to scale, though magnified for convenience of represen- 
tation ; and from these as well as from the calculated numbers, it will be seen 
that, when the limb was horizontal, the area of the internal calibre was more 
than three times as great as in the elevated position, and that, when it was depen- 
dent, the capacity of the tube was increased about sevenfold. 

The more we consider these facts, the more clear is it that they cannot be 
accounted for as merely mechanical results of diminution and increase of the 
pressure of the blood upon the arterial walls, in consequence of the different 
effects of gravity upon the fluid in the tubes in different positions. The arteries, 


METACARPAL ARTERY OF HORSE 


SECTION LIMB 
AFTER REMOVAL] ELEVATED 


AREA OF AREA OF AREA OF AREA OF 
CALIBRE CALIBRE CALIBRE CALIBRE 
12:5 40 132 276 


in any given state of contraction of their transversely arranged muscular fibres, 
are by no means disposed to yield readily in the lateral direction to increase, 
of pressure from within. This is evident from the fact that they are not in- 
creased in diameter by the successive strokes of the powerful muscular pump, 
the heart. The surgeon, when tying a large arterial trunk in its continuity, 
does not find, on clearing the vessel of its sheath with the point of his knife, 
that he is dealing with a body that swells at every pulse, but with one of unvarying 
dimensions. And, in the experiment on the metacarpal artery of the horse 
above referred to, no changes in the transverse measurements were noticed so 
long as the limb was maintained in any one position.! If any increase do occur 


length ; so that the material composing its wall was thinned out, not only in consequence of lateral 
expansion, but also to some slight degree through longitudinal stretching. 

’ Professor A. W. Volkmann, in his valuable work, Die Haemodynamik, relates experiments which 
he made by forcibly injecting water into portions of arteries removed from the body, proving that they 
yielded in the transverse direction even more than in the longitudinal to pressure from within. But 
Volkmann wrote before the discovery of the vaso-motor nervous system (he published in 1850), other- 
wise he would have been well aware that his experiments on dead animals left out of account altogether 
the most important element in this question, viz. the muscular contraction of the vessels as distinguished 
from mere elasticity. Volkmann admits that, when an artery is laid bare in the living animal, the only 
perceptible evidence of expansion of the vessel during pulsation is the tortuous form assumed by it 
at every pulse in consequence of longitudinal stretching, and that the transverse distension which he 
supposes to take place on theoretical grounds is inappreciable. Even in the dead vessel, he could 


N 2 


180 EFFECTS OF THE POSITION OF A PART 


in the diameter of an artery in systole, it is inappreciable by ordinary methods 
of measurement. 

Yet, the increase produced in the pressure of the blood upon the arterial 
walls by the ventricular contractions is certainly very great. When the coronary 
artery of the lip is divided in a child in the operation for hare-lip, the little 
fountain of blood that springs from the cut vessel may be sometimes seen to 
rise about twice as high in systole as in diastole, implying that even in so small 
a branch, in spite of the equalizing tendency of the elasticity of the tubes of 
transmission, the systolic pressure of the blood is double the diastolic. 

The tracings given by the recording haemodynamometer, and reproduced 
in modern physiological works to illustrate the variations of the blood-pressure, 
though very interesting in some respects, are entirely untrustworthy as indi- 
cations of the relative pressures of systole and diastole. For, in all such 
instruments, the apparatus opposes more or less resistance to the altering pres- 
sure, and time is required to overcome that resistance, so that rapid variations, 
such as those of the cardiac pulsations, are most inadequately represented. 

With reference to the present inquiry, I was anxious to obtain definite 
information on this important point ; and it occurred to me that this might be 
simply and surely done by making the blood write its own record, by means of 
a stream issuing from a minute orifice in a tube tied into an artery, the projected 
blood being allowed to fall upon a horizontal sheet of paper drawn smoothly 
past the animal. By such an arrangement, the effects of the varying degrees 
of pressure of the blood would be observed untrammelled by any resisting 
apparatus ; and, as the range of projection is directly proportioned to the 
projecting force, a comparison of the distance to which the blood was thrown 


not obtain evidence of transverse yielding by measurement with the compasses, but only by calculation 
from the observed increase in length which the vessel experienced when over-distended with liquid, 
together with the increase in the volume of the tube, as indicated by the additional weight of water 
which it admitted, vide op. cit., pp. 407, 422, and 423. The impressions conveyed to the finger in 
feeling the pulse, and also the indications of the sphygmograph, are no evidence of expansion in the 
cylindrical tube. In both cases, pressure is made upon it, producing a more or less oval condition of 
the transverse section of the vessel; and the impulse experienced is essentially the result of a tendency 
to restoration to the circular form as the blood-waves pass through the constricted part. A precisely 
similar pulse is produced in a cylindrical tube of inelastic but flexible material, through which a fluid 
is forcibly driven in a jerking stream. In an actual experiment made to illustrate this point, the in- 
elastic tube was formed of a strip of thin macintosh cloth, with its edges stitched closely together. 
One end of this tube was connected with a piece of caoutchouc tubing, through which water was driven 
by a force-pump, while the other end of the inelastic tube was continued in another piece of caoutchouc 
tubing, the distal end of which had a somewhat narrow glass tube tied into it to simulate the resistance 
in the capillaries, and ensure a continuous though jerking stream by bringing into play the elasticity 
of the caoutchouc and of the air in the air-chamber of the pump. At every stroke of the pump, the finger, 
placed on the inelastic tube of macintosh, experienced a sensation exactly similar to that in feeling 
the pulse. When the pulse is visible in the human subject, the appearance is unquestionably caused 
by the movements of the vessel, as it becomes alternately curved and straightened in systole and diastole. 


ON tH, CIRCULATION THROUGH IT 181 


in systole with the distance in diastole, as indicated by the curve formed by the 
drops sprinkled on the paper, would afford perfectly trustworthy evidence of 
the relative amounts of systolic and diastolic pressure. In an experiment of 
this kind performed upon a dog under chloroform, but with the circulation very 
active, a curved glass tube being tied into the external carotid, with an orifice 
only -0075 of an inch, so small in proportion to the calibre of the common carotid 
that the outlet could not materially affect the blood-pressure, the stream which 
issued from the tube, inclined at an angle of about 45 degrees, was projected 
twice as far in systole as in diastole. And very similar results were obtained with 
a tube tied into the common carotid of a rabbit operated on without anaesthesia.! 
We are, therefore, not far wrong in considering the pressure of the blood upon the 
walls of a considerable artery as doubled, in normal circulation, through the 
contraction of the ventricle. 

Now, we have no reason to suppose that the elevation of the leg of a horse 
from the horizontal to the vertical position, or vice versa, would produce a greater 
difference than this in the pressure of the blood upon the arterial walls. The 
original manometrical experiment of Stephen Hales, though performed with 
comparatively rude apparatus, is strikingly illustrative of this point. Having 
tied into the femoral artery of a horse a brass tube adapted to a long one of glass 
held in the vertical position, he found that the blood rose in the glass tube to the 


* Dr. Burdon-Sanderson has pointed out to me that I have not been the first to make the blood- 
stream write its own record upon paper. In 1874, which is before the date of the experiments mentioned 
in the text, Dr. Leonard Landois of Greifswald published, in Pfliger’s Archives for Physiology, an account 
of what he terms Hamautographie, and gave photographic representations of tracings obtained by 
drawing a piece of paper past an animal in which he had opened an artery, so that the stream of blood 
was received upon the paper. These tracings are very beautiful, especially from the light they throw 
upon the phenomenon of dicrotism of the pulse and the respiratory curve, but they were not designed 
to estimate the relative force of systolic and diastolic pressure, and no inference can be drawn from 
them with reference to that question. Instead of having a tube tied into the artery with an orifice so 
small as to have no appreciable effect upon the tension of the blood in the vessel, as in my experiments, 
the stream was allowed to flow from the divided artery either directly or through a tube of uniform 
calibre inserted into it to prevent closure of the orifice ; and instead of having the paper placed hori- 
zontally at a given distance from the artery, to show the range of projection, he held it perpendicularly 
to the stream, and no mention is made of its distance from the vessel. 

* It may perhaps be objected, that the results of the experiments described in the text cannot be 
taken as a fair indication of the increased pressure upon the arterial walls in systole, because, in the 
actual circulation, motion of the blood is produced as well as tension, whereas these two effects are 
confused together in the experiments, inasmuch as the stream which issues from a tube tied into an 
artery is the result of the entire force of the heart. This would be a valid objection if the actual amount 
of the tension upon the vascular parietes were the object of inquiry, but it has no force whatever against 
an estimate of the relative amounts of the systolic and diastolic pressure ; or, to speak more strictly, 
the increase of tension in systole is underestimated by the method of experimenting ; because, when 
fluid is injected through a tube offering a certain amount of resistance to its passage (as is the case in 
the vascular system), an increase of the force with which the liquid is injected produces less propor- 
tionate increase of motion than it does of tension; and, therefore, a method of experimenting which 
represents the effects of the entire force of the circulation, without distinguishing between motion and 
tension, underrates the increase of tension at the higher pressures. 


182 EFFECTS 0F ‘THE POSITION OF A PART 


height of 9 ft. 8 in. above the level of the left ventricle,t whereas the distance 
from the level of the heart to that of the metacarpal artery, where I operated, 
is only about four feet. That is tosay, the column of blood from the level of the 
heart to that of the artery, when the limb was raised, had not half the height 
of that which the force of the heart was able to sustain in one of the main 
arterial trunks. Now we know that the pressure of the blood is not materially 
less in arteries of secondary dimensions, like the metacarpal, than in the main 
trunks.? And therefore the raising of the limb into the vertical position could 
not, as the mere result of the action of gravity upon the blood, diminish the 
pressure of the fluid upon the arterial wall by as much as one half ; or, conversely, 
the putting the limb down again could not do so much as double the pressure 
of the blood upon the vessel. 

Seeing, then, that the doubling of the pressure which results from the 
contraction of the ventricle has no appreciable effect upon the diameter of an 
artery, it appears clear that the great alterations in the size of the metacarpal 
artery of the horse which resulted from varying the positions of the limb cannot 
be explained on mere hydrostatic principles, and that, in order to account for 
them, we must admit contractions and relaxations of the muscular coat of the 
arteries in obedience to nervous action. 

That the force of the heart is amply adequate in the human subject to 
drive the blood freely through the vessels of the distal parts of a limb, in spite 
of the elevated position, provided that the arteries are relaxed, I shall now have 
the means of plainly demonstrating. The constricting band has been on this 
man’s arm for eight minutes, yet, thanks to its efficacy as a tourniquet, the limb 
remains as pale and corpse-like as when the application was made, although he 
has kept his hand down in the interval. I shall now ask him to raise the hand 
again to the utmost degree ; and, while it is so placed, I shall remove the elastic 
bandage. This having been done, you observe that the skin of the hand is begin- 
ning to show patches of redness, and now, a few seconds more having elapsed, 
even the finger-tips, as well as the rest of the limb, are of florid red hue. The 


' See Statical Essays. By Stephen Hales, D.D., F.R.S. 1769. 

* Poiseuille, the inventor of the mercurial haemodynamometer, believed, as the result of his experi- 
ments, that there was no appreciable difference in blood-pressure between vessels of much greater 
divergence in size. Thus, in one of his experiments (see Poiseuille, Recherches sur la Force du Ceur, &c., 
1828, p. 36), he found that the mercury rose to the same height in the haemodynamometer in the 
carotid of a horse as in a muscular branch of the femoral only two milimetres in diameter, whereas 
the metacarpal artery on which I operated had fully two and a half times that dimension. Marey, 
indeed, states (Circulation du Sang, 1863, p. 150) that the mean tension of the arteries decreases 
as the vessel is situated further from the heart, and as its calibre diminishes. But, though this is no 
doubt strictly true, yet it is allowed by physiologists that ‘ the fall’ in pressure ‘is a very gradual one 
until the smallest arteries are reached’ (Michael Foster, A Text-book of Physiology, second edition, 
1878, p. 102). 


ON THE? CIRCULATION THROUGH IT 183 


veins, you see, remain collapsed, the blood being continually drained out of them 
by the action of gravity; but the arteries, in spite of that action, instead of 
being empty or nearly so, as they were when the limb was previously elevated, 
are distended even to the remotest capillaries. He will now raise the other 
hand, and you observe the extraordinary contrast between the two limbs, both 
in the elevated position, the hand last raised becoming as pallid as the other 
did before the elastic band was applied. 

It is worth while to consider shortly how it is that the constricting bandage 
gives rise to arterial relaxation. It is well known that troublesome after-bleeding 
not unfrequently follows the application of Esmarch’s bloodless method. This 
is commonly attributed to a temporary paralysis of the vaso-motor nerves, in 
consequence of the pressure to which they have been subjected. Now, in the 
experiment which you have just witnessed, one of the two factors in Esmarch’s 
method which might be supposed to have such an effect—viz. the tight elastic 
bandage, applied from the distal extremity upwards, and temporarily com- 
pressing the branches as well as the trunks of the nerves—is absent ; so that 
we have merely to consider the effect of the constricting band upon the nervous 
trunks at the root of the limb. It is no doubt true that in the arm, where the 
soft parts are in small proportion to the cylindrical bone, if, instead of an elastic 
bandage, an india-rubber tube be employed as the constricting agent, in accor- 
dance with Esmarch’s original proposal, the concentrated pressure so exerted 
may, in case of a protracted operation, lead to paralysis of a very troublesome 
if not serious character, both of motion and sensation. But if we follow Esmarch’s 
more recent advice, and diffuse the pressure by using the broad bandage, no such 
effects are observed. I have tried the experiment upon myself, and I have 
found that the bandage, applied sufficiently firmly to arrest all circulation and 
sufficiently long to produce the after-blush in the raised limb, did not affect 
in the slightest degree either the sensation of my hand or the motor power of 
the forearm. And as there is no reason whatever for believing that the vaso- 
motor fibres in the trunks of the nerves are more likely to suffer from com- 
pression of those trunks than the sensory and voluntary motor fibres, the theory 
of paralysis from compression falls to the ground. That which seems to me to 
be probably the true explanation is, that when a part has been deprived for 
a while of circulation, the want of the vital fluid creates in the tissues a demand 
for a supply of it, and that this demand operates upon the vaso-motor nervous 
apparatus of the limb as a stimulus inducing arterial relaxation, in a manner 
perhaps analogous to that in which the ‘ besoin de respirer’, as the French 
have termed it, produces a stimulus to the respiratory nervous system. We 
know that in the case of the arteries different stimuli produce different effects ; 


184 ; EPFECTS OF THE: POSITION OF (A PART 


cold inducing reflex arterial contraction, while heat occasions, equally through 
the nervous system, a relaxation. According to this view, then, the necessity 
for circulation, if I may so express myself, is a stimulus to dilatation which, 
when sufficiently urgent, overpowers the stimulus to contraction occasioned 
by the diminution of pressure upon the vessels in the elevated position. And, 
as a matter of fact, we find that the after-blush is greater the longer the time 
during which circulation has been arrested, although without anything to indicate 
nervous paralysis. In complete harmony with this view are the phenomena 
observed in a limb after ligature of its main artery. When the femoral is tied 
for popliteal aneurysm, the first effect upon the foot is pallor and coolness ; but, 
after the lapse of some hours, the converse condition of abnormal redness and 
heat supervenes. Here there is certainly no interference with the nerves, but 
the usual supply of blood is in the first instance notably diminished ; and, as 
a consequence of this, long before there has been any possibility of organic 
increase in the vessels, the anastomosing branches become so much dilated as 
to more than compensate for the obstruction of the principal source of supply. 
This effect can only be brought about through the nervous system ; and the 
most natural explanation seems to be that deficient circulation in a part continued 
for a considerable time comes to operate as a stimulus to arterial relaxation. 

I have now to mention an experiment which any one may easily perform 
upon himself, but which, though extremely simple, is not on that account the 
less instructive. But first let me state the considerations that led me to it. 
If the contraction of the arteries of an elevated limb were really the result of 
an action of a particular part of the nervous system, it might be expected that, 
on the cessation of the stimulus that evoked it, an unusual relaxation would 
ensue, corresponding with a period of repose of the nervous apparatus concerned ; 
and that this would be more marked the greater and more protracted had been 
the effort. Supposing, then, that the hand were raised after the circulation had 
been brought into full activity by brisk exercise, with the heart working power- 
fully and the arteries generally in a state of considerable dilatation, if, in spite 
of these unusual obstacles to arterial contraction, pallor of the limb should 
result from the elevated position, it might be anticipated that, when the hand 
was again lowered, it would not only resume its former redness, but acquire for 
a while a deeper tint than the other, which had been kept dependent throughout. 
My first trial of this kind was made just after I had been walking with great haste 
to catch a train, when my heart was beating with unusual vigour, and my hands 
were of florid colour. Having raised my left hand, I saw it become, within half a 
minute, very pale, and on putting it down after it had been a minute in that 
position, I observed it grow, within a quarter of a minute, much deeper in arteri- 


ONG GEE CrRCULATION THROUGH IT 185 


ally red tint than the right, a difference which gradually passed off, so that, 
in the course of one minute and three-quarters, the hands were again of equal 
colour. Two minutes later, I repeated the experiment, and this time kept the 
left hand raised for two minutes, and then, on lowering it, found it to become in 
ten seconds much redder than the other, which had been suspended the whole 
time ; and, just as might have been expected after the more protracted action 
of the nervous apparatus, the repose was longer in duration, so that, even after 
two minutes and twenty seconds, when I was obliged to start for the train, 
the left hand was still shghtly the redder of the two. Now such a result as this 
was entirely contrary to what could be explained as a consequence of mere 
hydrostatic laws. If the arteries had been simply emptied in the elevated 
position by the force of gravity, all that could have resulted on restoring the limb 
to the dependent posture would have been a return more or less rapidly to 
the previous condition of vascular fullness. And it is an interesting fact that 
the veins, though comparatively thin-walled, and much more readily distensible 
than the arteries, do not at once recover their former size when the elevated 
limb is lowered, but remain for a while markedly less turgid than those of the 
other hand, even when, through arterial dilatation the colour of the skin is not 
only more florid but manifestly darker. Hence this apparently trivial experi- 
ment, if duly considered, seems to me of itself sufficient to prove the truth of 
the doctrine for which I am contending. 


ON THE APPLICATION OF A KNOWLEDGE OF 
HYDROSTATICS AND HYDRAULICS TO PRAC- 
TICAL MEDICINE’ 


Abstract of an Address delivered before the Medical Society of University College, London 
on October 11, 1882. 


[Lancet, 1882, vol. ii, p. 638.] 


REFERRING to Mr. Beck’s remark, in his excellent introductory lecture,’ 
that physiology is the application of chemistry and physics to the study of life, 
Mr. Lister said that it would naturally be expected that physics would be one of 
the subjects in which medical students would be compelled to show a certain 
amount of proficiency. By the latest regulations of the Medical Council students 
could be registered without giving evidence of any knowledge of physics, and as 
this subject was not required by the Royal College of Surgeons, these students 
could, and no doubt would, become registered practitioners without such 
training. In view of this, he proposed to show some of the practical uses in 
medicine of a knowledge of the simple facts of hydraulics and hydrostatics. 

Mr. Lister then first referred to the fact that fluid always maintains 
the same level in communicating tubes of different calibre, and from that 
passed on to describe the ‘ hydrostatic paradox’ and the Bramah press. As 
a practical application of this principle he adduced the treatment of a wound 
of one of the palmar arches. Insuch a case it was necessary to enlarge the wound 
sufficiently to see the exact bleeding-point, and to place the apex of a graduated 
compress exactly on this point ; for if the compress were inaccurately applied, 
the blood finding its way out of the wounded artery would convert the wound 
into a kind of Bramah press, and either force up the compress or distend the 
interstices of the softer tissues. From this Mr. Lister passed on to consider 
some of the simpler facts about fluids in motion. For this purpose he had a vessel 
of coloured water raised above the table, from which depended a rubber tube 
connected at its end with a fine glass nozzle. Allowing the fluid to flow through 
this apparatus, he noted the height of the jet of water, and then replaced the 
middle of the tube by an equal length of tube of double the diameter and four 


* Note by Lord Lister, April 1908: The account of this Address here given was published without 
my authority, and, though fairly accurate as a condensed report, is, as was natural under the circum- 
stances, very imperfect. 

* Lancet, 1882, vol. ii, pp. 559, 607. 


6 a sore aie 


HYDROSTATICS AND HYDRAULICS IN PRACTICAL MEDICINE 187 


times the capacity, and pointed out that, the force remaining the same, the 
height of the fountain of fluid was practically the same. He used this experi- 
ment to show that large varicose veins do not increase the labour of the 
heart or impede the return of blood to the heart, and that those writers 
who made such statements were evidently ignorant of simple physical laws. 
He next held the tube at various elevations, and showed that the position 
of the tube did not influence the height of the fountain or the flow of 
blood through the tube, and therefore the effect on the blood circulation 
of raising or depressing a limb could not be explained on simple hydraulic 
principles, except in so far as the increased or diminished blood-pressure might 
cause distension or shrinking of the blood-vessels. And how were the facts 
to be explained, that raising the head of a debilitated patient may cause syncope 
and anaemia of the brain, and depressing the head of a fainting person will 
infalliibly cure the faintness and restore the circulation in the brain? What 
was wanted was relaxation of the arteries; the mere action of gravity would 
tend rather to the dilatation of the veins, and as the brain is contained in a closed 
rigid cavity, it was impossible to explain the facts on mere hydraulic principles. 
Mr. Lister stated that many years ago he had a horse slung and laid bare one of 
the metacarpal arteries ; 1f, now, he were held with the foot dependent the 
wound bled freely, and the artery was dilated and pulsated freely, while when 
the horse was inverted and the hoof raised in the air the wound ceased to bleed, 
and the artery contracted and ceased to pulsate visibly ; in the horizontal 
position the condition was intermediate. Stephen Hales, who was a vivisector, 
though a divine, had shown that the blood-pressure in the carotid of a horse 
raised a column of blood seven feet high, and it was clear, therefore, that the 
effect in Mr. Lister’s experiment was not due simply to the action of gravity. 
Further, when a large artery, such as the femoral, is exposed for the purpose 
of applying a ligature around it, the vessel is seen to be of a constant size ; the 
pulse does not affect its calibre even when it is measured accurately by calipers ; 
the vessel becomes slightly elongated, but the circular muscular fibres do not 
permit of lateral yielding of the vessel to any degree, and yet the blood is altered 
enormously during the cardiac systole. In reference to this, Mr. Lister warned 
his hearers against being misled by certain pulse-tracings in physiological 
works, in which the effects of respiration on the pulse were shown by large curves, 
and that of the cardiac systole by only short notches in the line, as if the effect 
of respiration on the arterial pressure was much greater than that of the heart. 
The explanation was that the effect of the heart’s contraction took some time 
to show itself, and before it was fully recorded by the apparatus it was inter- 
rupted by the diastole. He had himself, many years ago, performed the 


188 HYDROSTATICS AND HYDRAULICS IN PRACTICAL MEDICINE 


following experiment :—Tying into the external carotid artery of a dog a glass 
tube with an aperture less than one-hundredth of an inch in diameter (so that 
the loss of blood should be insignificant), he directed the fine fountain of blood 
on to a sheet of white paper, which was regularly moved along; in this way 
a tracing was made by the blood itself, which showed that the arterial pressure 
during the systole was double that during diastole. 

From these facts it is evident that we must look to the vaso-motor system 
to explain the cause and cure of a fainting-fit by position of the head, and the 
effects of position upon the blood-flow. When a limb is raised, blood flows 
down by gravity and the veins are relaxed, and we can imagine that an afferent 
stimulus is thus excited which, reflected along the vaso-motor nerves, contracts 
the arteries. If, however, the tissues are kept for a long time ill supplied with 
blood, there is such a demand set up for this fluid that the vessels dilate even in 
spite of the elevated position of the limb, which originally caused anaemia. 
This was illustrated by the well-known experiment of keeping one arm raised 
above the head and the other dependent, the former becoming pale and the 
latter turgid. An elastic band was then rapidly wound round the upper part 
of the elevated arm, and when, after a few minutes, this was removed, the whole 
limb became suffused and redder than its dependent fellow. Illustrations of 
the working of this principle were to be seen in the sequence to the ligature 
of a large artery, the limb at first becoming cold and pale from mechanical 
cutting off of the blood-supply, and then hot and suffused from dilatation of the 
vessels as a result of tissue-starvation. For the same reason, in piles and 
affections of the pelvic viscera raising the lower limbs gave great relief, for the 
contraction of the arteries was not limited to the limbs, but spread to the vessels 
of the pelvis. As a further instance, he mentioned the case of a man who 
suffered extreme pain in his testicles when in an upright position, but was imme- 
diately relieved by sitting down and putting up his feet. Raising the arms 
above the head too was a well-known means of stopping epistaxis, and suc- 
ceeded, because the contraction of the arteries of the arms spread by sympathy 
to those of the Schneiderian mucous membrane. Mr. Lister concluded by stating 
that he hoped that the few illustrations he had been able to give would show 
the value of a knowledge of hydrostatics and hydraulics, especially as indicating 
where physiological effects were produced by other than physical causes. 


ON THE COAGULATION OF THE BLOOD 
INU TTS PRACTICAL ASPECTS 


The Annual Oration to the Medical Society of London, delivered May 4, 1891. 


[British Medical Journal, 1891, vol. i, p. 105.] 


Mr. PRESIDENT AND GENTLEMEN.—Thirty years ago, Dr. Alexander 
Schmidt, of Dorpat, enunciated a totally new view of the coagulation of the 
blood. Having rediscovered the fact observed many years before by Dr. Andrew 
Buchanan, of Glasgow,’ that hydrocele fluid—uncoagulable in itselfi—is made 
to coagulate by the addition to it of the serum of blood already coagulated, and 
pursuing extended researches in the line thus indicated, he came to the conclusion 
that fibrine does not exist as such in solution in the plasma, but is composed of 
two albuminoid substances, one present in the liquor sanguinis, to which he gave 
the name of fibrinogen, and the other a constituent of the blood-corpuscles, 
and this he termed the fibrinoplastic substance.” 

It might be objected to Professor Schmidt that the hydrocele fluid and the 
various dropsical effusions with which he had worked were not fairly comparable 
to liquor sanguinis ; that they were transudations through the walls of vessels, 
and that the liquor sanguinis might have become in one way or another altered 
in the process of transudation. This objection was, as I believe, removed by 
an observation made by myself about the same period.*? It had fallen to my 
lot to observe that in mammalia, whereas the blood usually coagulates soon 
after death in the heart and the main vascular trunks, in the secondary vessels 
it remains fluid for an indefinite period, and that not only in those of small 
calibre, but, if the animal be large, in large vessels also. This being understood, 
I proceeded as follows : Having removed a portion of the jugular vein of a horse 
with the blood contained in it, between two ligatures, I suspended this segment 
of the vein in a vertical position. In the blood of the horse, the red corpuscles 
behave in a totally different manner as regards their aggregation from those 
of a healthy man or of the ox. In the horse, instead of the red corpuscles 


1 Proceedings of the Glasgow Philosophical Society, February 19, 1845. 

* Archiv fiir Anat. Phys., &c., 1861 and 1862. 

3 The Croonian Lecture, by the author, ‘On the Coagulation of the Blood,’ Proceedings of the Royal 
Society, 1863, p. 606 (page 109 of this volume). 


1gO ON THE COAGULATION OF .THE BLOOD 


assuming the condition of a delicate network of rouleaux, they become aggre- 
gated into dense spherical masses, often visible to the naked eye, like coarse grains 
of sand ; and these densely aggregated corpuscles, falling more quickly than the 
rouleaux in the liquor sanguinis, as hailstones fall more rapidly than snow- 
flakes, soon leave the upper part of the fluid comparatively free from corpuscles ; 
so that within about half an hour the upper third, or it may be half, of the blood 
is a transparent liquid.!’ When I had ascertained through the translucent walls 
of the vein that this state of things had occurred, I punctured the upper part of 
the vessel, so as to let out some of the clear fluid, and found that it was very 
slow in coagulating. In about three-quarters of an hour it had only begun to 
coagulate, whereas a little of this same clear fluid, to which a small portion of 
coagulated blood was added, clotted in a very short period. That the clear 
fluid did coagulate at all was sufficiently explained by microscopical examina- 
tion, which showed that there were present in it some red corpuscles and 
numerous white corpuscles. It was obvious that if we could have separated 
the corpuscles absolutely from the liquor sanguinis, there would have been no 
coagulation at all; and as the separation of the corpuscles from the plasma 
had occurred, not by transudation through vascular walls but simply as the 
result of gravity, it could be no longer doubted that Schmidt’s conclusions were 
essentially right. 

During the time that has since elapsed various endeavours have been made 
to ascertain the precise nature and mutual relations of the constituents of the 
liquor sanguinis and the corpuscles thus concerned in the formation of the fibrine. 
This inquiry cannot be said to be yet terminated, and it is, at the present time, 
uncertain whether Schmidt’s simple original view may not be correct, that there 
are two albuminoid substances, one in the plasma and one in the corpuscles, 
which combine to constitute fibrine. 

These investigations, most valuable as they are, have, as it seems to me, 
somewhat overshadowed the question, which is after all the most interesting 
to us as practitioners, namely, What are the circumstances that determine the 
mutual reaction of these two constituents ? What are the conditions under 
which the corpuscles are induced to give up their element of the fibrine, to combine 
with the element in the liquor sanguinis ? This subject engaged a large share 
of my attention many years ago; and, though I am afraid I have not much of 
novelty to communicate regarding it, yet in consequence of its very great impor- 

‘ The same thing is seen in the mixture of serum and corpuscles obtained by stirring the blood 
during coagulation. In that from the horse the red corpuscles subside from about the upper third of 
the liquid within half an hour; whereas that from the ox shows only a thin layer of serum after the 


lapse of twenty-four hours. I am surprised to see that in some textbooks the buffy coat is attributed 
to slowness of coagulation. 


iN Tas PRACTICAL ASPECTS IgI 


tance, I have thought that it might perhaps be not unworthy of the circum- 
stances in which the kindness of your Council has placed me this evening. 
Shortly before my investigations began, Professor Briicke, of Vienna, had 
conducted an inquiry into the conditions which determine coagulation, and had 
arrived at conclusions which to a certain extent resembled those to which I was 
led.t. He found, as I also did, that there is a world-wide difference, in their 
relations towards the blood, between the walls of the living vessels and ordinary 
solid matter ; and Briicke concluded, as Sir Astley Cooper and others had done 
before him, that this difference consisted in an active state of the living vessels ; 
that the blood-vessels, by an action which they exerted upon the blood, prevented 
it from coagulating. My investigations, on the other hand, led me to conclude 
that healthy blood has no spontaneous tendency to coagulate ; and that the 
walls of the blood-vessels are not active, as Briicke supposed, but passive in their 
relation to coagulation ; that ordinary solids induce coagulation by an attractive 
influence—comparable, perhaps, to that which a thread exerts in causing the 
deposition of sugar-candy from a solution of sugar—while the healthy living 
tissues differ from ordinary solids in being destitute of this attractive influence. 
Out of many experiments tending to this influence, published long ago,’ 
I may be permitted again to describe one which not only appears to me conclusive 
on the point at issue, but is also of interest otherwise. A portion of the jugular 
vein of an ox with the blood in it being held vertically, I cut off the upper end, 
taking scrupulous care that the wounded part of the vessel did not come in contact 
with the blood, and then passed down into the vein a tube composed of very 
thin glass of a calibre rather less than that of the jugular vein, its upper end 
being stopped by a perforated cork in which was inserted a narrow glass tube, 
which again was continued with a short piece of vulcanized india-rubber tubing. 
The tube was pressed with the utmost steadiness down into the vein, so as to 
disturb the blood as little as possible. In the course of time, the vein being 
a little squeezed, blood made its appearance in the narrow glass tube, and then 
at the end of the india-rubber tube. When this was the case, the india-rubber 
tube was secured by a clamp, and the whole apparatus was rapidly inverted, and 
the piece of vein withdrawn. Waterproof tissue was then tied over the open 
end of the large tube to prevent evaporation and exclude dust, and the tube 
was securely fixed and left undisturbed. Thus we had blood present in a 
vessel consisting entirely of ordinary solid matter, but having been subjected 
in a minimum degree to the influence of the ordinary solid: and the result was 
that when I came to examine the blood after the lapse of ten hours, I found it 


' British and Foreign Medical Review, 1857. 
* The Croonian Lecture, Proceedings of the Royal Society, loc. cit. 


192 ON THE COAGULATION OF THE BLOOD 


still fluid, with the exception of a crust of clot lining the wall of the vessel. 
This, gentlemen, seemed to me of itself to afford sufficient evidence that healthy 
blood has no spontaneous tendency to coagulate, requiring to be kept in check 
by an action on the part of the walls of the living vessels. This blood had 
been entirely withdrawn from the vein, and yet it remained fluid except where 
in contact with the ordinary solid. 

This conclusion has been comparatively lately strikingly confirmed by the 
experiments of more than one observer. I would especially allude to one per- 
formed by Professor Berry Haycraft.1 He has found that if a drop of blood 
is introduced, under suitable precautions, into a deep narrow jar of castor oil, 
and before the drop, which falls slowly through this oil, has reached the bottom 
of the vessel, the jar is inverted, and the drop made to retrace its steps without 
having touched the glass, this process being repeated again and again, the drop 
of blood, having never come in contact with an ordinary solid, remains fluid 
for an indefinite period. This experiment may perhaps appear to some of you 
even more conclusive than mine, inasmuch as no coagulation whatsoever occurs 
in the drop of blood under these circumstances. Certainly it seems to me that 
it confirms in an absolutely unmistakable manner the view to which I had been 
previously led. 

But there is also this interesting circumstance in Professor Haycraft’s 
observation. It had been shown amply by myself that the gases of the atmo- 
sphere are incapable of inducing coagulation of the blood; but experiments 
like those of Professor Haycraft show that the same is the case with neutral 
or chemically indifferent iguids. This seems to me to be an exceedingly inter- 
esting fact, namely, that the active living tissue, such as lines the wall of a 
healthy vessel, in its relation to the coagulation of the blood, resembles the 
mobile particles of a liquid. I say the active living tissue ; for when the living 
tissue becomes impaired in vital energy, it behaves towards the blood like an 
ordinary solid. That is the case not only when a vessel is wounded, but also 
when it is subjected to some influence which, without actually wounding it, 
is calculated to suspend or impair its vital activity. A good illustration of this 
is afforded by a fact which I have never before referred to, but which I have often 
noticed. A very valuable field for simple and instructive observations regarding 
the conditions that determine the coagulation of the blood was afforded by the 
feet of sheep, removed after the animals had been killed, the blood being retained 
in the vessels by a bandage applied below the part where the foot is removed 


* Journal of Anatomy and Physiology, vol. xxii, p. 582. 
* Dr. Freund, of Vienna, almost simultaneously and independently observed this relation of inert 
liquids to coagulation, Jahresberichte fiir Anatomie und Physiologie, 1886. 


Peis PRACTICAL ASPECTS 193 


by the butcher. The blood remains fluid for days in the veins of such feet, 
while, at the same time, the persistent vitality of the vessels is shown by the fact 
that they contract when exposed by reflexion of the skin.1 Now it happened 
that the butcher, in order to keep the sheep from struggling, always tied the 
feet together with a firm cord applied below the part where my bandage for 
retaining the blood was passed round ; and I invariably found the blood coagu- 
lated in the superficial veins at the part where they had been pinched between the 
cord and the bone. There is no reason to suppose that the temporary application 
of the cord had deprived the veins of their vitality at the part subjected to its 
pressure. If the sheep had been released, I have no doubt whatever that the 
veins would have remained alive. But though the vessels had not been wounded 
but only squeezed, only had their vital energies temporarily impaired, never- 
theless the blood had coagulated in them at the part so treated. Just as by 
pinching a portion of the web of a frog’s foot with the padded ends of a pair of 
dressing forceps you can induce, by the irritation of mechanical violence, an 
intense degree of inflammatory congestion, in which the pigment cells for the 
time being have their vital functions of diffusion and concentration of the pig- 
ment perfectly suspended, and yet are in a condition which is recoverable,” so 
did these veins, subjected to a similar agency, experience, though unwounded, 
a temporary prostration of their vital power. Thus it appears that the living 
tissues, which, while in a healthy active state, differ from ordinary solids in not 
occasioning the coagulation of the blood, themselves act like ordinary solids, and 
induce coagulation when their vital energies are suspended. 

Another point to which my investigations were at that time directed was 
the behaviour of the blood-clot in relation to coagulation. I came to the conclu- 
sion that, in a healthy state of the blood, an undisturbed coagulum resembles 
living tissue in its behaviour with regard to coagulation ; that an undisturbed 
clot does not induce coagulation in its vicinity is a most important truth if it 
be such. This is well illustrated by the fact with regard to the sheep’s foot, 
to which I have already referred. We have seen that, on the one hand, where 
the tight cord had pressed the veins, coagulation occurred in those veins, but 
on the other hand that the blood remained permanently fluid in other parts of 
the same vessels. In other words, the clot induced by the action of the cord 
upon the veins had not been able to spread, although the blood in the veins 
was perfectly at rest; the clot could not propagate itself. The same thing is 

* The blood in the amputated limb becomes gradually impaired in its coagulating property. A few 
hours after amputation it is found to clot more slowly than at first when exposed to the influence of 
ordinary solids, and after some days fails to coagulate at all. 

* See a paper by the author ‘On the Early Stages of Inflammation’, Phil. Tvans. Part I, for 1858, 


p. 682 (page 209 of this volume). 
LISTER I O 


194 ON THE COAGULATION OF THE BLOOD 


seen in any amputated limb in which the blood-vessels are sound. If such a limb 
is examined, say twenty-four hours after amputation, you will find that there 
exist clots in the vessels where they were wounded by the knife in the operation, 
but that elsewhere the blood remains fluid and coagulable. I came, therefore, 
to the conclusion that an undisturbed blood-clot is unable to induce coagulation 
in its vicinity ; and I think that the instances I have given demonstrate that such 
is really the case. 

Yet in the experiment which I have described, where a glass tube was slipped 
down into the jugular vein, the coagulum did propagate itself. I found, as 
before mentioned, on examining such a tube ten hours after it had been charged 
with blood, that the crust of clot which lined the tube was only a thin one ;_ but 
in another experiment, nearly two days having been allowed to pass before 
examination, the layer of clot was thick, and there remained only a small channel 
in the middle of it, with the blood still fluid and coagulable. How is this dif- 
ference of behaviour between the clot within the vessels and the clot outside them 
to be explained ? At the time when I performed the experiment, I was disposed 
to think that it must be due to some imperfection in the mode of performing 
it; that in spite of all the care that I had taken in very steadily pressing down 
the very thin glass tube, nevertheless the blood must have been influenced by 
the glass for some considerable distance. 

Iam now inclined to believe that another explanation must be given. It 
was ascertained by Schmidt that (to adopt provisionally his original nomen- 
clature) the fibrinoplastic substance emitted by the corpuscles is in excess of 
what is required in order to combine with the fibrinogen of the liquor sanguinis. 
This, in fact, is obvious from the fundamental truth that serum expressed from 
a shrinking clot, when added to hydrocele fluid, induces coagulation. The blood 
is coagulated already ; the fibrine is already formed in it; and yet the serum 
contains fibrinoplastic substance in solution free to combine with the fibrinogen 
of the hydrocele fluid. Such being the case, we see that, in the experiment with 
the glass tube, the clot first formed under the influence of the glass, shrinking 
and squeezing out its serum containing fibrinoplastic substance, this must com- 
bine with the fibrinogen of the adjacent liquor sanguinis, forming fresh fibrine, 
and producing a new layer of coagulum. 

This, however, will only account for a very limited extension of the clot ; 
inasmuch as the fibrinoplastic substance of the original coagulum having now 
all completely combined with fibrinogen, none will remain in solution, and thus 
the serum pressed out by the shrinking of the new layer will not contain fibrino- 
plastic substance, unless some new agency comes into play, to induce the cor- 
puscles of the last-formed coagulum to give it up. Such an agency is, I suspect, 


INS PRACTICAL ASPECTS 195 


present in the shrinking of the fibrine, which, as a matter of theory, seems quite 
as likely to have such an influence on the blood-corpuscles as the attractions of 
an ordinary solid. If such be the true state of the case, the clot must go on 
perpetuating itself indefinitely, however slowly.’ 

But how are we to explain the non-extension of the clot within the vessels 
in the cases referred to ? How are we to explain the fact that it did not spread 
from the vicinity of the tight cord in the sheep’s foot, and does not extend beyond 
the vicinity of the wound in the amputated limb? Again, why is it that the 
coagulum never propagates itself from the wound in the vein after phlebotomy ? 
That wound—intentionally made somewhat gaping—is certainly, in the first 
instance, occupied by blood-clot. The equable flow of the venous blood does 
not disturb it. It is an undisturbed coagulum. But it must often happen that 
the clot projects more or less into the calibre of the vessel, in which case the 
blood, at its lee side, will lie at rest in contact withit. Yet the indefinite extension 
of the coagulum, which the analogy of the blood in the glass tube would lead 
us to anticipate, never occurs; and we reckon with confidence on the wound 
in the vein simply healing without interference with its calibre. 

These remarkable differences between the behaviour of a coagulum in a glass 
tube and within the living vessels may, perhaps, have light thrown upon them 
by a fact which I have on a previous occasion brought before the attention of 
this Society. I first observed it, eighteen years ago, in an attempt that I made 
to obtain pure blood-serum from a horse; letting blood, with antiseptic pre- 
cautions, from the carotid artery into a flask that had been purified by heating 
it toa very high temperature. To my great astonishment, I found that, although 
the blood of the horse coagulated as usual in the flask, the clot did not shrink 
in the least. Though I kept it for many days, yet there was not a drop of 
serum to be seen upon its surface, and the sides of the clot remained in contact 
with the wall of the flask. This was made particularly striking by the circum- 
stance that masses of aggregated red corpuscles, resembling grains of sand, 
as before described, were to be seen touching the glass in the lower part of the 
buffy coat. This, I need hardly say, astonished me immensely ; and I imagine 
it was the first time that a blood-clot was ever seen not to shrink and press out 
serum. 

It seemed hardly likely that this result could be due to the destruction of 
micro-organisms in the flask, although the heat had been applied for that purpose. 


* A good example of the indefinite extension of a clot outside the body is mentioned by Freund 
(op. cit.).. He found that, while blood might be kept fluid for an indefinite period in a vessel completely 
coated with paraffin, if the coating was deficient at any point, coagulation took place there and spread 


throughout the mass. 
O02 


196 ON THE COAGULATION OF THE BLOOD 


It was suggested to me that perhaps it might arise from some physical change 
in the glass due to the very high temperature to which I had subjected it. It 
had been observed by Liebig that, whereas a supersaturated solution of sulphate 
of soda is, under ordinary circumstances, made to start into a crystalline mass 
by contact with a glass stirring rod, no such effect is produced by the rod if it 
is heated in the flame of a spirit lamp and allowed to cool; a result attributed 
by Liebig to some temporary physical change produced in the glass by the heat. 
Might it be, then, that the fibrine of the clot failed to shrink in consequence 
of a different molecular arrangement assumed under the influence of the glass 
altered by heat? That view, however, has been exploded; because it has 
been proved, as illustrated by some striking experiments shown at a conver- 
sazione of the Royal Society some years ago by my colleague, Professor Thomson, 
that the cause of the crystallization of the supersaturated solution of sulphate 
of soda is not the contact with the glass as such, but the accidental presence 
on the glass of minute quantities of sulphates isomorphous with the sulphate of 
soda ; and that the effect of the heat is to drive off the water of crystallization 
of those salts, and make them no longer isomorphous with it, and, therefore, 
no longer able to induce the crystallization. And so a mystery in physics was 
cleared away, and made a very simple matter. Thus the suggested explanation 
fell to the ground. 

The same absence of shrinking of the clot had been brought about by different 
means in the example which I exhibited to this Society nearly seven years ago.1 
A glass jar, not especially clean, had been purified by means of a solution of 
corrosive sublimate in 500 parts of water. Blood had been let into this jar from 
the jugular vein of a horse, under antiseptic precautions, forty-one days before ; 
and the members of the Society had the opportunity of seeing that, just as in 
the case of the flask subjected to a high temperature, the clot had not shrunk ; 
the serum had not been squeezed out of it. And although it seems unlikely 
that in the short time that elapses between the shedding of the blood and the 
commencement of shrinking of the clot under ordinary circumstances, the micro- 
organisms present could have had such an influence on the blood, yet when we 
see that two agencies so different in their nature as a high temperature and a 
solution of corrosive sublimate, but both powerfully germicidal, led to the same 
result, one is almost inclined to think that surely it must beso. No other explana- 
tion has been offered, although I know that physiologists have been much 
interested in the subject. 

If we admit that micro-organisms are the cause of the shrinking of the clot, 
and that the shrinking of the clot is the cause of its extension, it follows that 


' British Medical Journal, 1884, vol. ii, p. 803 (see p. 293 of volume ii of collected papers). 


Pets PRACTICAL ASPECTS 197 


an undisturbed coagulum formed within the body under healthy conditions 
otherwise, being free from micro-organisms, will not spread. Fibrinoplastic 
substance exists, no doubt, in the serum in the substance of the clot. But the 
experiments of the late Mr. Graham showed that diffusion of liquids is an exceed- 
ingly slow process, even between a strong saline solution and water ; and it must 
be a very slow process indeed between two liquids so nearly allied as liquor 
sanguinis and serum. 

Whether this explanation be correct or not, the fact remains that an 
undisturbed clot of healthy blood within healthy living vessels is incapable 
of self-propagation.1 On the other hand, the theory which I have sug- 
gested is in harmony with the extension of clots containing microbes, as in 
pyaemia. 

While an undisturbed clot resembles healthy and active living tissue with 
respect to coagulation, a disturbed and torn clot acts in this relation like wounded 
tissue. And as a coagulum is an easily lacerable substance, we often see coagu- 
lation induced by a blood-clot that has been disturbed. This is perhaps most 
strikingly seen in aneurysm. Let us take, for instance, a traumatic aneurysm. 
The blood escapes from the wounded artery into the surrounding tissues ; and 
these having been injured, the blood coagulates in contact with them. Every 
successive portion of blood driven in by the force of the ventricle stretches and 
lacerates the clot so formed. It is an injured clot, and induces coagulation in 
its vicinity : and the result comes to be that while, on the one hand, the force 
of the heart tends perpetually to distend the sac, inferior as it is in elasticity 
to the wall of the artery, there is on the other hand a constant tendency to deposi- 
tion of fibrine upon the interior of the sac, as if the blood were ‘ whipped’, and 
thus the wall of the sac is perpetually strengthened, exhibiting a counteracting 
agency tending to recovery. 

A beautiful converse of this state of things is presented, as it seems to me, 
by some cases of varicose aneurysm, such as used to be a not uncommon result 
of careless venesection. Here the communication with the vein was sometimes 
so free that the blood driven in by the heart distended the sac comparatively 
little, so that the aneurysm had no tendency to increase, but was merely a source 
of annoyance from the purring sensation caused by the arterial blood driven 
into the vein. And if an operation was performed on such a case, the remarkable 
fact was disclosed that instead of the aneurysmal sac being lined with layers 


? As further illustrations of this important truth may be mentioned the limitation of the coagula 
to the immediate vicinity of the wound in the veins of a stump after amputation; and also the fact 
which I have often noticed that if a varicose vein in the leg is treated by removing portions of the vessel 
at intervals of a few inches, the blood, though it coagulates in the immediate vicinity of the ligatures 
employed, remains permanently fluid in other parts of the vein. 


198 ON THE COAGULATION OF THE BLOOD 


of fibrine, it resembled in its interior an artery or a vein.’ The force of the blood 
not being able to tell upon the clot and disturb it, the clot ceased to induce 
further coagulation, and became organized and invested with endothelium. 

We see the same thing illustrated in the different behaviour of the blood- 
clot above and below a ligature applied upon an artery in its continuity. When 
such a ligature was applied in the old-fashioned way, in the shape of a silk thread, 
used without any antiseptic precautions, with the ends left long, it had to come 
away by suppuration, and there was serious danger of secondary haemorrhage. 
But if this did occur, it was commonly not, as might have been expected, from 
the cardiac side, where the seat of ligature was subjected to the full force of the 
ventricular contractions, but from the distal side, where the pressure was com- 
paratively feeble. The lgature having been applied sufficiently tightly to 
rupture the internal and middle coats, there necessarily occurred as an imme- 
diate result a certain limited amount of coagulation upon the injured tissues. 
On the cardiac side, where the force of the blood driven by the heart against 
the obstruction told powerfully at every stroke, the clot was perpetually dis- 
turbed, and infallibly coagulation occurred up to the first considerable branch, 
producing a substantial resisting plug. But at the distal side, if the circumstances 
of the anastomosing circulation were such that there was no pulsation, there 
might be no extension whatever of the undisturbed primary coagulum, so that 
a mere trace of clot was found on pathological examination. 

I have hitherto dwelt on the view first advanced by myself and now, I believe, 
generally accepted—that the fluidity of the blood is not due to an active operation 
of the living vessels. But I am far from holding the opinion that there is no 
part of the vascular system that actively opposes coagulation. If transfusion is 
practised in the ordinary manner—say by filling a syringe with blood and 
injecting it into the veins of the patient—the blood is subjected to the influence of 
an ordinary solid, which would inevitably induce coagulation within the vessels, 
unless there were some counteracting agency at work. It is astonishing how 
very short a period of contact with an ordinary solid determines the mutual 
reaction of the corpuscles and the liquor sanguinis. Yet no coagulation 
occurs as the result of such an operation. It is, I presume, in the capillary 
system that the correcting influence is exerted. 

Again when intense inflammatory congestion is produced by the application 
of some irritant substance to the web of a frog’s foot, we see that the corpuscles, 
both red and white, adhere to one another and to the walls of the vessels, and 
block the capillaries. Mechanical violence is one of the many irritating agencies 
which produce such congestion ; and from what we know of the effects of the 


* Syme’s Principles of Surgery, 5th edition, p. 140. 


IN ITS PRACTICAL ASPECTS 199 


pressure of the cord upon the veins of the sheep’s foot, we cannot doubt that the 
blood must be coagulated in the congested vessels : that between the corpuscles 
there must be cementing fibrine. The distinguishing characteristic of acute 
inflammatory exudation is of itself pretty clear evidence to this effect. The 
exudations in intense inflammation differ from those of dropsy by being coagu- 
lable ; hence the brawniness of tissues that are intensely inflamed, or the lymph 
in acute pericarditis. How can this coagulable character of the effused liquor 
sanguinis be explained except by supposing that the walls of the capillaries 
have acted for the time being like ordinary solid matter, and that, as a con- 
sequence of this behaviour of the capillaries, the corpuscles have given up to 
the liquor sanguinis (to use Schmidt’s language) the necessary fibrinoplastic 
substance ? And if the exuded liquor sanguinis coagulates, we cannot doubt 
that the plasma which remains in the capillaries is also coagulated. Nevertheless, 
if the irritant has not been pushed so far as to cause the death of the part on 
which it has acted, the tissues in due time recover, and we see the corpuscles 
gradually detaching themselves from each other, to pass on into the circulation. 
And we may surely say that, not only do the corpuscles recover their original 
non-adhesive character, but the fibrine which binds them together is dissolved. 

I believe, therefore, that although in the larger vessels the vascular walls 
are negative as regards the coagulation of the blood, in the capillary system 
there must be potent agencies counteracting any tendency to clotting induced 
by abnormal conditions, and capable even of dissolving fibrine. 


PART Il 
PATHOLOGY AND BACTERIOLOGY 


NOTES OF THE EXAMINATION OF AN EXOSTOSIS 
REMOVED BY MR. SYME ON OCTOBER 2, 1853, 
FROM THE OS HUMERI OF A YOUNG LADY 
AGED ABOUT TWENTY YEARS 


Read to the Edinburgh Medico-Chirurgical Society, November 16, 1853. 


[Monthly Journal of Medical Science, January 1854.] 


THE tumour was situated at the posterior and inner aspect of the bone, 
two or three inches from its upper end. Some idea of its general appearance 
may be gathered from Fig. 1 of the accompanying woodcut (see next page), 
which gives a lateral view of it of the natural size. It is seen to be of irregular 
form, presenting at its most prominent part several smooth rounded tuber- 
osities : these were covered with cartilage, while the more circumferential parts 
of the tumour rose gradually from the normal level of the bone around, and 
were destitute of cartilage. The whole surface of the tumour was invested 
with extremely loose cellular tissue, which must have allowed very free gliding 
motion of superjacent parts; this cellular tissue adhered firmly, both to the 
cartilaginous and osseous portions of the surface. At a, a piece of the tumour 
had been broken off, exposing the cancellated texture of the interior, which in 
the deepest parts of the exostosis, was extremely loose, consisting of medullary 
substance traversed by very delicate spicula, which presented the microscopical 
characters of true bone (a lacuna with canaliculi from one of these spicula was 
shown in a sketch at the reading of the paper). In the circumferential parts 
of the tumour, which, as above stated, were destitute of cartilage, this loose 
cancellous structure extended to within a very short distance of the surface, 
which was formed by a thin layer of compact, true osseous tissue. But beneath 
the cartilaginous prominences there was a considerable thickness of compact 


202 NOTES OF THE EXAMINATION OF 


substance, of a peculiar white aspect, too gritty and friable for true bone, and 
having a dark confused appearance under the microscope, with no definite 
structure ; but after maceration in dilute hydrochloric acid presenting both to 
the naked eye, and under the microscope, the characters of cartilage. As a 
general rule, this calcified cartilage was present in greatest amount where the 
cartilage was thickest. Fig. 2 exhibits part of a section made perpendicular 
to the surface of one of the prominences of the exostosis; a is the cartilage 
covering the surface, and is upwards of a line in thickness ; the calcified cartilage 
b immediately beneath it was very dense, while at e the texture was looser, 


Fic. 1 is a lateral view of the exostosis: at @ a piece of the tumour has been broken off, and the loose structure 
of the interior shows itself. 

Fic. 2 exhibits part of a section through one of the prominences of the tumour: a is the superficial cartilage ; 
c isa portion of cartilage situated deeply, and surrounded on all sides by dense calcified cartilage, b and 
d; e is the deepest part of the calcified cartilage, of looser texture than the more superficial parts. 

Fic. 3 shows a section of a portion of the tumour at the line of junction of the calcified cartilage and the 
cancellous structure of the interior; the earthy matter has been removed by dilute hydrochloric acid : 
a is the cartilage with its cells changed by the process of calcification; b c is true bone (containing 
lacunae) lining the excavations in the calcified cartilage; d is part of a spiculum of the cancellous 
structure: e and / are spaces formerly occupied by medullary substance. 


but even there, at a depth of five-eighths of an inch below the surface, cartilage 
cells showed themselves after maceration in acid. 

The microscopical appearances of the superficial cartilage presented nothing 
very remarkable ; the cells were larger than they are found in human articular 
cartilage, and many of them were of rather complex structure ; they were much 
elongated at the free surface, where, indeed, it was difficult to distinguish them 
from the contiguous part of the investing cellular tissue ; while in the deeper 
part of the cartilage they were more or less elongated in a direction perpendi- 
cular to the surface of calcification (a figure was shown representing one of 
these deeper cells). The matrix was homogeneous or faintly granular. The 
matrix of the calcified cartilage as seen after maceration in acid, was more 


AN EXOSTOSIS REMOVED BY MR. SYME 203 


granular, and the cells were rounder, and often surrounded with a broad pellucid 
ring, but the cells of the immediately adjacent part of the uncalcified cartilage 
assumed more or less of the same characters. The boundary between the 
uncalcified and the calcified cartilage was rendered very distinct by the circum- 
stance that the matrix of the former was coloured brown by the action of the 
acid, while that of the latter generally remained colourless. 

At one spot, viz. at c in Fig. 2, a piece of cartilage existed at a considerable 
depth below the general surface of calcification, and surrounded on all sides 
by the dense pseudo-bone ; this cartilage was extremely soft, and its cells re- 
markably large; one of them of circular outline measured 1~—285th inch in 
diameter ; the nuclei also presented considerable variety of appearance, and 
complexity of structure. It might be supposed that these characters of the 
cells were connected with great rapidity of growth in this cartilage, and such 
may perhaps be the case; but the cells are not larger than exist in the central 
parts of costal cartilages. In the centre of a costal cartilage of a woman about 
sixty years old, I found cells very similar both in size and appearance, and it 
can hardly be supposed that any very rapid cell-development had been going 
on in that situation at such a period of life. 

The fact that the calcified cartilage was in some places looser in texture 
at its deep than at its superficial parts (e.g. looser at e than at ) in Fig. 2) seems 
to indicate a change going on in the calcified cartilage by which it becomes 
converted into the loose cancellous structure of the interior. Examination of 
the deepest parts of the calcified cartilage under a low magnifying power, after 
the earthy matter has been removed by acid, shows that it is invaded by pro- 
cesses of the medullary substance of the cancellated tissue beneath it, which 
advance for a variable distance into its substance, and give a very irregular 
eroded character to its outline. The excavations thus seen to occur in the 
deep border of the calcified cartilage, are often lined with a thin layer of true 
bone containing lacunae, which has, no doubt, been deposited subsequently 
to the formation of the excavations. Fig. 3 represents a small portion in this con- 
dition, where a is the deepest part of the calcified cartilage, b c is a layer of true 
bone lining the excavations e and /, which were formerly occupied by processes 
of the medullary substance ; and d is part of one of the spicula of the cancellous 
structure. The true bone is distinguished from the matrix of the calcified 
cartilage by having a higher refractive power than it. 

In the part where I first noticed this osseous lining of the calcified cartilage, 
it was almost universally present; very few of the excavations being even 
partially destitute of it. And the same appearance presented itself in the head 
of a metatarsal bone of a boy sixteen years of age, at the line of junction between 


204 NOTES OF THE EXAMINATION OF 


the epiphysis and the cartilage which separated it from the shaft. Indeed, the 
resemblance between the two objects was exceedingly close, for the disposition 
of the cartilage cells in piles perpendicular to the surface of ossification, while 
present in the shaft of the metatarsal bone, was absent alike in the epiphysis, 
and in the exostosis; also the part of the cartilage that was immediately con- 
tiguous to the newly formed bone of the epiphysis was evidently calcified, and 
closely resembled the calcified cartilage of the exostosis, both in the condition 
of the cells and in the eroded form of its margin; the eroded edge, again, was 
almost universally lined with a layer of true bone exactly as in the exostosis, 
except that the layer was generally somewhat thicker. 

These facts appeared at first inconsistent with the idea of the layer of true 
bone having been deposited subsequently to the formation of the excavations, 
for that supposition implied that both in the epiphysis and in the exostosis, 
the process of excavation of the calcified cartilage had almost entirely ceased, 
or, in other words, that the conversion of the calcified cartilage into true bone 
was almost or altogether suspended; and this appeared particularly unlikely 
in the case of the exostosis, which was known to have been growing rapidly 
before its removal. 

The examination of the ossifying epiphysis of one of the bones of a calf’s 
foot has, however, convinced me that the layer of true bone is deposited on 
the walls of previously existing excavations. The cells of the calcified cartilage 
are there seen to enlarge at the expense of the matrix as they approach the 
cancellous structure of the epiphysis, and at the same time to acquire a granular 
appearance, just like that of the rudimentary medullary substance with which 
the last formed areolae are filled; and finally, they evidently form by their 
coalescence the excavations in the margin of the calcified cartilage. Those 
parts of these excavations or areolae which are farthest from the perfect bone, 
and which have been last formed, are devoid of any osseous lining; but at 
a very short distance from their extremities they acquire upon their surface 
a thin layer of lacunated bone, which is seen to increase gradually in thickness 
at the expense of the cavities as they are traced nearer to the perfect bone. 

A further examination of the exostosis also showed that in some parts the 
osseous lining of the margin of the calcified cartilage was absent, while, on the 
other hand, there appeared at these parts evidence of a change in the deepest 
cells of the calcified cartilage, like that observed in the calf’s foot, viz. an en- 
largement of the cells, and a conversion of their contents into a granular sub- 
stance previous to their coalescence to form the excavations. 

It thus appears that the process by which the calcified cartilage of the 
exostosis was converted into the cancellous structure of the interior, is essentially 


AN EXOSTOSIS REMOVED BY MR. SYME 205 


the same as what occurs in the ossification of the epiphysis of a metatarsal bone. 
The only difference between the two cases appears to be that in the ossifying 
epiphysis, the calcified cartilage is a very thin layer, while in the exostosis it 
is present in considerable thickness ; but even in this particular there was not 
a constant difference between them ; for the calcified cartilage varied much in 
thickness at different parts of the exostosis, and at some spots was, to the naked 
eye, absent or nearly so, even where cartilage existed on the surface. 

The great thickness of the calcified cartilage probably results, in part at 
least, from a want of energy in the process by which it is converted into the 
cancellated tissue, and accordingly it was just at that part where the calcified 
cartilage was thickest (viz. at e in Fig. 2) that the osseous lining of the calcified 
cartilage was found almost universally present ; and we have seen that this 
condition implies an arrest in the process of conversion of calcified cartilage into 
cancellous structure. The languid condition of the ossific process at this part, 
was probably also the cause of the piece of cartilage c in Fig. 2 being left uncal- 
cified below the general level of calcification. 

The general conclusion to which the examination of this exostosis leads, 
is that it grew at the surface as cartilage, which became converted into can- 
cellated bone by an ordinary process of ossification, in which, however, the stage 
of calcification of cartilage occupied an unusually conspicuous position. 


REPORT OF A CASE OF CARBUNCLE 


OCCURRING IN MR. SYME’S PRACTICE, ILLUSTRATING 
ESPECIALLY THE PATHOLOGY OF THAT DISEASE 


[Monthly Journal of Medical Science, July 1854.] 


THOMAS DAVIDSON, aet. 52, admitted into the Royal Infirmary, February 9, 
1854, a weaver, residing at Sinclairton near Kirkcaldy. States that he has 
generally enjoyed good health, and that three weeks before his admission he 
was in no respect worse than usual; he had been in full work and had eaten 
and drunk his usual quantity without excess in either respect. At this time 
his attention was directed by a sensation of itching to the back of his right 
shoulder, and on putting his finger to the part, he found a small elevation about 
as big as a barley-corn and very tender to the touch. This grew rapidly and 
became the seat of intense pain, and continued to increase in size till his admis- 
sion, but had been less painful for a few days preceding it. When he came 
to the Infirmary a large elevated mass existed behind the right shoulder, of 
circular form, about six inches in diameter, rising gradually from the level of 
the skin around: of livid red colour surrounded by brighter redness of an inch 
or two of the adjacent skin. Its circumferential part was of brawny consistence, 
while the central part was soft and pulpy, but not fluctuating, and in this central 
part there were numerous small circular apertures, which did not admit the 
probe for more than a very short distance; the instrument could be passed 
a little way under their margins, which were formed by a vascular superficial layer 
as thin as paper. At the centre of the tumour these openings were confluent. 

On the day of the patient’s admission Mr. Syme made a very free crucial 
incision through the tumour, extending down to its very base, and reaching a 
little way into the bright red surrounding skin. A good deal of bleeding occurred, 
and the colour of the tumour became rapidly and very remarkably changed to 
a pale bluish-red tint. The cut surface, which in the centre measured nearly 
two inches perpendicularly, presented numerous small collections of pus scat- 
tered through it, and many spots of yellow lymph; the rest of the tissue was 
evidently the dermis expanded by the inflammatory exudation, and towards 
the centre of the tumour in a shreddy sloughy state. The patient was not 
under chloroform, and says he hardly knows whether the pain of the incisions 
was worse than that which he had suffered from the carbuncle a few days before 
admission. Mr. Syme ordered milk diet, which has been gone on with to the 
present time (February 14), while linseed-meal poultices have been applied 
twice a day. Under this treatment the carbuncle has daily improved, induration 
diminishing and the mass melting down, partly in the state of slough and partly 
in that of pus; the surrounding redness is almost totally gone, no extension 
whatever of the disease having occurred since the incisions were made. The 
pale tint of the skin that occurred at the time of the incisions never became 
deepened, except at one part, where the interval between the incisions was 
greater than elsewhere, and there it remained red and hard for a day or two ; 
but there also the free drain afforded by the incisions has some days ago removed 


REEOR I ROr  AICASE OF “CARBUNCLE 207 


both redness and induration. Two days after the incisions were made, he 
regained his appetite, which he had lost ever since the carbuncle became intensely 
painful, though not for several days after the commencement of the disease. 

A few days after I again made a careful examination of the affected part. 
At this time the sections of the carbuncle made by the incisions were assuming 
a healthy appearance, particularly towards the circumference of the mass. 
These sections were now covered with granulations, and this, together with 
their great thickness, gave them an appearance certainly very unlike that of 
sections of the dermis. The incisions had, however, extended a little beyond 
the carbuncle into the healthy skin around, and on tracing the sections outwards 
to the parts where the skin was healthy, I found that the thick diseased parts 
passed insensibly into the sound portions, whose sections were also covered 
with granulations, and differed from the diseased only in their thickness. 

The slough soon separated completely, leaving the external portion of each 
of the four flaps made by the crucial incision, and these gradually assuming 
the character of healthy skin, a granulating sore remained, whose cicatrization 
presented nothing remarkable. 


Remarks.—This case illustrates some important points in the pathology, 
aetiology, and treatment of carbuncle. Mr. Syme long since pointed out! that 
carbuncle is essentially a disease of the true skin, that it is by no means neces- 
sarily connected at its outset with an impoverished or enfeebled state of body, 
although, doubtless, dependent on some constitutional vice, and that being an 
inflammation of peculiar intensity, 1t requires in its early stages general anti- 
phlogistic treatment, and local blood-letting, in the form of free incisions, which, 
if practised sufficiently early, cut short the inflammation, and prevent it from 
running on to sloughing. 

The case before us was a typical example of carbuncle, and its commence- 
ment as a pimple in the skin combines with the appearances which it presented 
on admission to show clearly that the pathology above alluded to is correct, 
so far as this individual case is concerned. 

In a case of extensive carbuncle in the gluteal region which occurred about 
a month earlier, I was fortunate enough to obtain a slice from a part in an early 
stage of diseased action. This slice, which was cut perpendicular to the surface, 
included a small part of the subcutaneous fat, which was perfectly healthy. 
The dermis, however, was greatly thickened, and presented the appearance of 
numerous spots of greenish-yellow lymph intersected by bluish glistening bands 
of fibrous tissue, the dense structure of the corium being expanded into a loose 
network, in whose meshes the lymph lay. The only part of the dermis that 
did not contain more or less of this deposit of lymph was a very thin and highly 
vascular layer immediately beneath the epidermis. The microscope showed 
that the blood-vessels of the most superficial part of the corium, including the 


+ Vide Principles of Surgery, by James Syme, first edition, 1831, p. 610. 


208 REPORT OF A CASE OF CARBUNCLE 


papillae, were gorged with blood. This layer was about equal in thickness to 
the epidermis (which is thin in this region), and corresponds to the part which 
formed the margin of the openings in Davidson’s case, described in the above 
report as being as thin as paper. A superficial observer might suppose this thin 
layer to be the skin, and regard all parts beneath it as subcutaneous tissue ; 
but it required only a little careful observation to perceive its true relations. 
I confess that I had previously been accustomed to look upon carbuncle as 
essentially a disease of the subcutaneous tissue, but this slice convinced me, 
as it did every one to whom I showed it, that in that case at least the cutis vera 
was the seat of the disease ; and it is to be observed that this, like Davidson’s, 
was a fine example of the affection in question. No doubt, the subcutaneous 
textures may, and often do become affected secondarily, but the important 
practical fact which these two cases appear to establish, is that the great mass 
of a carbuncle is composed of thickened dermis, which may be freely incised 
without fear, whereas the subcutaneous textures in some regions contain im- 
portant parts which it is very desirable to avoid. It may be remarked that the 
extraordinary expansion which carbuncle produces on so dense, and, at the 
same time, so sensitive a structure as the dermis, sufficiently accounts for the 
intense pain that always accompanies it. 

With regard to the cause of the disease, it must be confessed that in the case 
above reported, none can be assigned. According to the patient’s own account, he 
was in strong active health at the time when the carbuncle commenced, neither 
plethoric nor the opposite, and no irregularity had occurred either in his diet or 
in his employment. The constitutional vice, of whatever nature, was latent. 

The free incisions made throughout the diseased mass were productive of 
the most palpable benefit, and evidently cut the disease short at once; and 
although the central part was already in the state of slough at the time of the 
patient’s admission, yet considering that the size of the tumour was then still 
increasing, I cannot doubt that the red brawny circumferential parts, which 
afterwards recovered their natural characters, would have sloughed if the in- 
cision had not been carried freely through them. As the disease yielded to the 
local treatment, the patient recovered his appetite, which he had long lost, 
but he never grumbled at his milk diet, although it was inadvertently continued 
much longer than Mr. Syme had intended. 

It will probably be tedious to some to read so minute a description of an 
affection with which they have long been familiar; but to those who do not 
happen to have examined the disease carefully themselves, and who know that 
a different pathology is commonly taught, the importance of the subject will, 
I hope, make the particulars which I have given acceptable. 


ON THE EARLY STAGES OF INFLAMMATION 


[Philosophical Transactions, Vol. cxlviii, Part II for 1858, p. 645.] 


Received June 18—Read June 18, 1857. 


INTRODUCTION 


Tue morbid process designated by the term Inflammation, being one to 
which every organ and probably every tissue of the body is liable, and com- 
prehending as it does in its progress and consequences by far the greater number 
of the ills to which flesh is heir, possesses a deeper interest for the physician or 
surgeon than any other material subject which could be named. The practical 
importance of inquiries tending to elucidate the essential nature of this process, 
has been for centuries recognized by all enlightened members of the medical 
profession ; for it is obvious that just views regarding it must tend to promote 
the establishment of sound principles in the treatment of the diseases which it 
produces. At the present day more especially, when theory is allowed such 
free scope, and is permitted to attack the most time-honoured rules of practice, 
we stand in peculiar need of the beacon-light of correct pathology to enable 
us to steer a safe course amid the various conflicting opinions which assail us. 
Yet so far from our knowledge of inflammation being in a satisfactory con- 
dition, authorities are at variance upon the fundamental question, whether it 
is to be regarded, in accordance with John Hunter’s opinion, as active in its 
nature, and consisting in an exaltation of the functions of the affected part, or 
whether it should not rather be considered a passive result of diminished func- 
tional activity. 

In seeking for the solution of this great problem, we cannot expect to gain 
much from the contemplation of the more advanced stages and results of inflam- 
mation, such as copious exudation of lymph, suppuration, ulceration, or gan- 
grene. When any one of these has taken place, the nature of the original disease 
is masked to a great extent by the subsequent changes ; and the cell-develop- 
ment which occurs in lymph after its effusion, is no more proof of activity in 
the inflammatory process, than the loss of the vital powers in gangrene can be 
accepted as evidence in the opposite direction. It is upon the first deviations 
from health that the essential character of the morbid state will be most un- 
equivocally stamped, and it is therefore to the early stages of inflammation that 
attention must be chiefly directed in this inquiry. 

If the palm of the hand be chafed by long-continued friction, as for example 


in rowing a boat, the first thing that will be observed, when attention has been 
LISTER I Pp 


210 ON THE EARLY STAGES OF INFLAMMATION 


directed to the part by a feeling of uneasiness, will be that the skin is redder 
than natural, implying that the vessels are abnormally loaded with blood, and 
if the irritation be continued, the cuticle will be raised in the form of a blister. 
If, now, the loosened epidermis be artificially removed on the earliest occurrence 
of effusion, a scarlet raw surface will be exposed; and on pressing the tender 
dermis firmly with the finger, and suddenly removing the pressure, it will be 
found that while the redness will for the most part have momentarily disappeared, 
there will be many minute red points from which the blood cannot be expelled. 
This shows that, while the blood is in part still free to move, there are some 
minute vessels completely clogged with it. Again, if a portion of mustard be 
placed on the skin covering the dorsal aspect of one of the fingers, abnormal 
redness will very speedily be produced, which in the first instance disappears 
completely on pressure; but, if the mustard has been kept on long enough, 
can be only imperfectly dispelled ; and if the application be still longer con- 
tinued, vesication will be the result. I had lately the opportunity of examining 
the brain of a man who had died of tetanus, complicated with incipient meningitis; 
the post mortem appearance of the latter being maculiform congestion of the 
pia mater. Having stripped off a portion of the affected membrane, and care- 
fully washed away with a camel’s-hair brush the cerebral substance adhering 
to it, I applied the microscope to one of the affected spots, and found that all 
the minute vessels were filled with crimson blood, while those of the surrounding 
parts were comparatively pale. It was evident that the red corpuscles were, 
in the former, so closely crammed together as to produce the appearance of a 
uniform mass, while in the latter they were present only in their usual proportion 
to the liquor sanguinis. Thus it appears that in the human subject, inflamma- 
tion, whether induced by mechanical irritation or by an acrid application such 
as mustard, or of spontaneous origin, is characterized at an early period by 
a certain amount of obstruction to the progress of the blood through the minute 
vessels ; a phenomenon, which it is therefore of great importance to understand. 

It fortunately happens, that we have, in the transparent web of the frog’s 
foot, an opportunity of observing with the utmost facility the circulation of 
the blood in the living animal, and of watching the effects produced upon it by 
irritating causes. It may naturally appear very doubtful whether observations 
made upon creatures so low in the animal kingdom as the amphibia, can with 
propriety be brought to bear upon human pathology. A few facts will, however, 
suffice to show that no such doubts need be entertained. If a portion of mois- 
tened mustard be placed upon the web of a frog, tied out under the microscope, 
the blood-vessels will soon be found abnormally red; and if the application be 
continued long enough, all the capillaries will become choked with corpuscles so 


ON THE EARLY STAGES OF INFLAMMATION 20T 


closely packed as to present the appearance of a uniform crimson mass; and 
by and by the epidermis will be found raised in the form of a blister over the 
part on which the mustard lay. These effects are precisely similar to those 
which we have seen to be produced by it upon the human skin; and before 
effusion has taken place, the vessels of the affected part exactly resemble those 
of the congested spot of inflamed pia mater above described. Again, if dry 
heat be made to act upon a part of the frog’s foot, there will result, in proportion 
to the elevation of the temperature and the duration of its action, undue redness 
of the vessels from accumulation of the blood-corpuscles ; and if the burn have 
been sufficiently severe, vesication will soon take place as in the human subject. 
These and other similar cases indicate that the early stages of inflammation 
are alike in man and in the frog, and this conclusion is fully confirmed by 
examination of the bat’s wing, which furnishes the means of watching the effects 
of irritants upon mammalian circulation. The very small size of the blood- 
corpuscles, and some other circumstances, render that animal much less suitable 
for the investigation than the frog; but with the use of high powers of the 
microscope and a little pains, the same sort of experiments can be made with 
both: and the careful observations of Messrs. Paget and Wharton Jones, and, 
I may add, also my own more limited experience with the bat, have shown that 
in all the details that can be observed, a complete similarity obtains between 
the effects of irritation upon the circulation in the two creatures. We may 
therefore rest fully satisfied that conclusions arrived at from the study of the 
early stages of inflammation in the foot of the frog will apply in all strictness 
to the same morbid process in man. 

It is well known that the field of observation thus afforded has not been 
allowed to remain uncultivated. Since the microscope has been brought to its 
present state of perfection, not to speak of a previous period, men of established 
scientific reputation have devoted much patient labour to it; and any one 
who now enters upon this inquiry has the great advantage of possessing faithful 
records of accurate observations made by many able predecessors. But the 
number and discordance of the views entertained by different authorities regard- 
ing the cause of the ‘ stasis’ of the blood in inflammation, are sufficient evidence 
either that the subject demands further investigation, or else that it les beyond 
the reach of human means of research. 

Having been called upon in the capacity of a teacher of surgery to attempt 
an explanation of the matter to others, I felt bound to do my best, by personal 
observation, to form a judgement for myself; and several new facts which 
I have unexpectedly met with appear to throw such fresh and clear light upon 
the nature of disease, that I venture to submit them to the Royal Society. 

P 2 


N 
H 
ho 


ON THE EARLY STAGES OF INFLAMMATION 


SECTION I 
On the Aggregation of the Corpuscles of the Blood. 


The tendency of the corpuscles of the blood to aggregate together, con- 
stitutes, as we shall see, an important element in the cause of the obstruction 
which they experience in the vessels of an inflamed part. It is therefore desir- 
able that we should be acquainted with the nature of the phenomenon. 

If a drop of human blood just shed is placed between two plates of glass 
and examined with the microscope, the red corpuscles are seen to become applied 
to one another by their flat surfaces, so as to form long cylindrical masses like 
piles of money, as first observed in 1827 by my father and Dr. Hodgkin; and 
the terminal corpuscles of each ‘ rouleau’ adhering to other rouleaux, a network 
is produced with intervals of colourless liquor sanguinis. Rapid movement of 
the blood prevents this occurrence, but it commences as soon as the corpuscles 
approach to a state of quiescence, and I have seen short rouleaux already present 
in a drop drawn from my own finger within ten seconds of its emission. In 
this respect the aggregation of the red corpuscles differs from the coagulation 
of the fibrine, which does not begin till some minutes after withdrawal from 
the vessels. There is, in fact, no connexion whatever between the two processes, 
as is clear from the circumstance that if a drop of blood is stirred with a needle 
while coagulation is taking place, so as to remove the whole of the fibrine, the 
corpuscles, which have been separated from one another by the agitation to 
which they have been subjected, aggregate again in the serum in the same 
manner as they did at first in the liquor sanguinis. The beautifully regular 
form of the long masses of corpuscles has suggested to some persons the idea 
of the operation of some peculiar vital attraction in their formation, while by 
others the aggregation has been supposed due to merely physical causes, but 
has never, I think, received a complete explanation. For my own part, I am 
satisfied that the rouleaux are simply the result of the biconcave form of the 
red discs, together with a certain, though not very great degree of adhesiveness, 
which retains them pretty firmly attached together when in the position most 
favourable for its operation, namely, when the margins of their concave surfaces 
are applied accurately together, but allows them to slip upon one another when 
in any other position. There is never to be seen anything indicating the exis- 
tence of an attractive force drawing the corpuscles towards each other: they 
merely stick together when brought into contact by accidental causes. Their 
adhesiveness does not affect themselves alone, but other substances also, as 
may be seen when blood is in motion in an extremely thin film between two 


ON THE EARLY STAGES OF INFLAMMATION 213 


plates of glass, when they may be observed sticking for a longer or shorter time 
to one of the surfaces of the glass, each one dragging behind it a short tail-like 
process ; and as the movement of the blood diminishes so as to permit the 
formation of rouleaux, the latter may be not unfrequently seen ad- => 
hering in the same way by one of their terminal corpuscles, as a> 
represented in the accompanying diagram. aS 

That the cylindrical character of the aggregated masses is an accidental 
result of the shape of the blood-discs, is evident from 
the fact, that in the frog, although the same ten- 
dency to agglutination of the corpuscles exists as 
in mammalia, yet, as their biconvex form renders 
it mechanically impossible for them to be applied 
to one another throughout their entire circumference, 
they become arranged in groups of an irregular 
form, as is shown in the annexed sketch of blood 
contained in a small vein of the frog’s web. 

Again, different specimens of mammalian blood differ very much in the 
amount of adhesiveness of their corpuscles; and when this property exists 
beyond a certain degree, the discs stick together by any parts that happen to 
come first in contact, and retain that position more or less, so that the result 
is the formation, not of rouleaux, but of irregular confused masses. The most 
striking example which I have seen of this was presented by the blood of a bat, 
which had lived some days after having been severely wounded. In that case, 
chains of red discs might be seen adhering firmly by their edges, notwithstanding 
considerable force of traction operating upon them, and before they at last gave 
way tail-like processes of considerable length were drawn out between every 
pair of corpuscles, indicating that they were very adhesive. These facts seem 
sufficient proof of the correctness of the view above expressed regarding the 
cause of the rouleaux. 

The adhesiveness of the red corpuscles does not appear to be a vital pro- 
perty. When the fibrine has been removed from a drop of blood during the 
progress of coagulation, the rouleaux will form again, after being broken up, 
as many times as the experiment is repeated, until the blood becomes thick 
from dryness ; and if evaporation be prevented by Canada balsam placed round 
the plate of thin glass, with suitable precaution against the approximation of 
the two plates, the rouleaux will remain perfect for several days (e.g. fourteen 
in one experiment of the kind), after which the very slow chemical action of 
the balsam upon the blood gradually renders it confusedly red and opaque. 
Gum mixed with blood seems to preserve it, like a pickle, from decomposition 


214 ON THE EARLY STAGES OF INFLAMMATION 


for a very considerable period ; and if a piece of wet lint be suspended above 
such a specimen so as to prevent evaporation, the corpuscles will retain their 
adhesiveness for a long time (e.g. twenty-four days in one instance), until the 
water communicated to the mixture by the artificially damp atmosphere grad- 
ually renders them non-adhesive. These experiments were made in winter, 
when the low temperature prevents rapid decomposition ; but it appears unlikely 
that even at that period of the year a part of the human body should retain 
any vital properties after having been left three and a half weeks mixed with 
strong gum, which, it is to be observed, alters very much the form and appear- 
ance of the corpuscles. 

Both in man and in the frog the white corpuscles also are found aggregated 
together more or less in a drop of blood examined microscopically, and indeed 
they adhere much more closely than the red ones both to the glass and to one 
another ; but as they are not disc-shaped, but globular, they do not become 
grouped into rouleaux, but into irregular masses, which, in consequence of 
their colourless and transparent character, are apt to pass unnoticed, or to be 
mistaken for masses of coagulated fibrine. If a portion of blood be allowed 
to run in between two plates of glass nearly in contact with one another, the 
white corpuscles will be found sticking together near the edge of the glass at 
which the blood entered, the blood having been as it were filtered of white 
corpuscles as it passed on ; and this is not due to the greater size of the colourless 
corpuscles than the red, for I have seen it occur with frog’s blood when there 
was room enough between the plates for the red corpuscles to lie edgewise, their 
transverse dimensions being greater than the diameter of a white corpuscle. 

The red corpuscles also often adhere to the colourless ones. 

It will be seen hereafter that the corpuscles of blood within the vessels of 
the living body present great varieties of adhesiveness, according to the amount 
of irritation to which a part may be subjected; such variations are also met 
with in blood outside the body, in consequence of differences in the quality 
of the plasma. 

If a drop of very thick solution of gum-arabic, freshly prepared and free 
from acidity, be added to about four drops of blood, the red corpuscles of the 
mixture will be found to aggregate much more speedily and more closely than 
those of ordinary blood, a fact ascertained some years ago by Mr. Wharton 
Jones and some other observers.’ The result is the formation of dense orange 
masses with large colourless interspaces, but without much regular appearance 
of rouleaux. On closely examining such a specimen, the red discs are seen 
to be much diminished in breadth and increased in thickness, and exhibit an 

* Guy’s Hospital Reports, vol. viii, p. 73. 


| 
| 
| 
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ON THE EARLY STAGES OF INFLAMMATION 215 


extreme degree of adhesiveness, sticking together indifferently by their edges, 
or any other parts that happen to come first; and if one of the masses be 
stretched so as to break, the separating corpuscles become drawn out into long 
viscid processes, which at length give way in the middle, and each half is drawn 
into its respective corpuscle. 

This remarkable effect cannot be accounted for by the mere viscidity of the 
plasma, which would not make the corpuscles adhere to each other more inti- 
mately than usual, unless they had themselves experienced some change, of 
which, indeed, their altered form is conclusive evidence. Further, if a very 
small quantity of acetic acid be added to the gum before mixing it with the 
blood, the corpuscles will be found to have lost altogether their adhesive char- 
acter, although the mixture may be made viscid to any degree that may be 
desired. A little acid perspiration on the finger appears to prevent entirely 
the formation of rouleaux in a drop of blood taken from it ; but after the finger 
has been washed, the usual appearances present themselves when more blood 
is drawn. Diminished adhesiveness of the red corpuscles is also the earliest 
evidence of the chemical action of tincture of cantharides and croton oil on the 
blood of the frog. A similar effect is produced when a drop of human blood 
is Shed into a little fresh almond or olive oil on a plate of glass, and stirred slightly 
so as to break up the blood into minute drops. On microscopic examination 
of such a mixture, one sees the red discs aggregated as usual in the interior of 
the larger drops; but at their exterior, which is in contact with the oil, and 
throughout the smaller drops, the corpuscles are somewhat altered in form, 
being of less diameter, but thicker, though still in the form of discs, and at the 
same time they are found to have lost every trace of a tendency to adhere to- 
gether ; and when present in a thin layer of blood they stand apart at equal 
distances from one another, as if exercising a mutual repulsion, at the same 
time exhibiting molecular movements. If a drop of blood freshly shed upon 
a glass plate be stirred with a needle in an atmosphere of chloroform vapour, the 
rouleaux will be found to form less perfectly in proportion to the time that the 
chloroform has acted, until, if the period be as long as thirty seconds, the cor- 
puscles will be all cup-shaped, and will exhibit no disposition to aggregate. 
But no effect is produced on the formation of the rouleaux by stirring a drop 
of blood in the same way for a much longer time in an atmosphere free from 
chloroform. The aggregation of the corpuscles is not prevented merely by 
their becoming cup-shaped, and therefore unable to apply themselves to each 
other as usual. For the vapour of caustic ammonia, while it renders the cor- 
puscles cup-shaped, seems rather to increase than to diminish their adhesiveness 
and aggregating tendency, and a temperature of about 32° Fahr. has similar 


216 ON THE EARLY STAGES OF INFLAMMATION 


effects with the alkali. Even in the mixture of blood and gum many of the 
corpuscles are cup-shaped, though adhering together with peculiar tenacity. 

Whether or not it will ever be possible to explain these curious facts upon 
chemical principles seems very doubtful; but in the meantime, what appears 
most striking about them, and what most concerns the present inquiry, is that 
great effects may be produced upon the adhesiveness of the red corpuscles, 
both in the way of increase and diminution, by very slight changes in the chemical 
qualities of the plasma. 

The galvanic current produces no effect upon the aggregation of the red 
corpuscles, either of man or of the frog, as I have ascertained by placing the 
fine platinum-wire extremities of the poles of a powerful battery a short distance 
from one another between two slips of glass beneath the microscope, then com- 
pleting the circuit by shedding a drop of blood between the plates, and imme- 
diately observing the result. In several such experiments I invariably found that 
aggregation took place as usual, and the only effect produced by the galvanism 
was a chemical change in the blood, dependent on electrolysis, gradually develop- 
ing itself in the immediate vicinity of the poles, and causing solution of the 
corpuscles. 

The buffy coat in inflammatory blood was first explained by Mr. Wharton 
Jones,? who showed that it resulted from the red corpuscles aggregating more 
closely than usual, and therefore falling more rapidly through the lighter plasma, 
so as to leave the upper portions completely before the occurrence of coagulation. 
It was supposed by the same authority that this peculiarity of the red discs 

* Since this paper was read, I was told by a gentleman well known in the scientific world, that he 
had observed, many years ago, that if blood was shed upon a plate of glass previously heated to the 
temperature of 100° Fahr., the red corpuscles showed no disposition to aggregation till the glass cooled, 
when the blood became killed, as he supposed, by the unnaturally low temperature. This appeared 
to me entirely irreconcilable with the fact that in the frog the red corpuscles aggregate immediately 
after the blood has been shed, although there is no material difference between the temperature of the 
air and that of the body of the animal. But, if true, it would have important bearings, to which I need 
not here allude, upon the essential nature of inflammation. I have therefore thought it well to make 
some experiments upon the point. The plate of glass upon which the blood was to be placed was warmed 
by immersion in water of a known temperature, and quickly but carefully dried. A drop of blood from 
my own finger was then at once shed upon it, and without loss of time covered with a piece of thin glass, 
which had been kept warm by being laid upon a metallic plate of the same temperature as the water. 
By proceeding in this way, I was able to make observations upon the blood very soon after it had been 
shed ; and when the glass was about 100° Fahr., the aggregating tendency was found just the same 
as in ordinary cases, and I detected short rouleaux already formed within five or six seconds of the 
escape of the blood from the vessels of the finger. The same state of things continued when the water 
was as high as 136°; but when its temperature was carried up to 155°, the red corpuscles lost their 
disc shape and some of them appeared to become broken up, and no rouleaux were formed either while 
the blood remained warm or after it had cooled. From these results, it is evident that heat does not 
interfere at all with the aggregating tendency of the corpuscles, unless it is sufficiently great to act upon 


them chemically. 
* British and Foreign Medical Review, October 1842. 


ON THE EARLY STAGES OF INFLAMMATION 217 


was due to increased fibrine in solution, rendering the liquor sanguinis abnor- 
mally viscid, and so operating like the admixture of gum above alluded to. 
But the fact that the corpuscles aggregate as closely after the fibrine has been 
removed as before, appears quite opposed to such a view. I have examined 
many drops of my own blood, before and after the removal of its fibrine, with 
the special object of ascertaining this point, and have never been able to detect 
any material difference between the aggregation in the two sets of cases. In 
the blood of the bat before mentioned, which was probably suffering consti- 
tutionally from inflammation, the corpuscles continued to retain their excessive 
adhesiveness for a whole hour after coagulation of the fibrine. I once made 
a similar observation on a specimen of horse’s blood,! which, as is well known, 
presents the buffy coat in the state of health. Having divided the clot vertically 
several hours after coagulation had occurred, my attention was attracted, on 
looking at the section, by minute red points, like grains of sand, lying in the 
lower part of the buff, just above the coloured portion of the coagulum. On 
microscopic examination of a small piece containing some of them, they proved, as 
I expected, to be masses of aggregated red corpuscles, but with the peculiarity of 
being compact and globular instead of presenting the usual appearance of a net- 
work of rouleaux, and it was evident that the corpuscles had been excessively 
adhesive at the time when aggregation took place. Some of the red discs 
were now squeezed out from the fibrinous mass in which they lay, and as they 
escaped into the surrounding serum they at once adhered firmly in that fluid, 
forming again compact globular masses, such as, if in freshly drawn blood, 
would necessarily give rise to the buffy coat ; so that their adhesiveness seemed 
to have been in no way affected by the withdrawal of the fibrine from solution. 
It may of course be urged, that the fibrine, when in solution, may have impressed 
upon the corpuscles an adhesiveness which they retained after soaking for hours 
in serum, but this seems a very unlikely hypothesis. I suspect, therefore, that 
the peculiarities of the corpuscles of inflammatory blood are the result of other 
changes than the excess of fibrine. 

From the facts detailed in this section, it appears that the aggregation of 
the corpuscles of blood removed from the body depends on their possessing a 
certain degree of mutual adhesiveness, which is much greater in the colourless 
globules than in the red discs; and that, in the latter, this property, though 
apparently not depending upon vitality, is capable of remarkable variations in 
consequence of very slight chemical changes in the liquor sanguinis. 


1 This observation was made subsequently to the reading of the paper, viz. in November 1857. 


218 ON THE EARLY STAGES OF INFLAMMATION 


SECTION II 
On the Structure and Functions of the Blood-vessels 


An acquaintance with the anatomy and physiology of the vascular system 
is indispensable to a successful study of the deviations from health exhibited 
in the circulation of the blood through the vessels of an inflamed part; it is 
not, however, intended to give here a full account of the subject, but merely to 
dwell upon some important points on which differences of opinion prevail. 

It has long been a debated question whether or not the capillaries possess 
contractility, and there is still some difference of opinion among authorities 
upon the subject. With a view to throwing light upon this important point, 
I investigated carefully the structure of the minute vessels of the frog’s foot ; 
dissecting them out from between the layers of skin composing the web, so as to 
render their constituent material capable of clear definition with the microscope. 
The chief results have been communicated to the Royal Society of Edinburgh, in 
a paper that will shortly appear in their Tvansactions, ‘On the Structure of 
Involuntary Muscular Fibre.’* I need therefore merely repeat here, that while 
the capillaries were proved to consist, as has been long known, merely of a delicate 
homogeneous membrane beset with occasional nuclei, the minute arteries, some 
of them even less in calibre than average capillaries, were found to possess three 
distinct coats, namely, an external layer of cellular tissue, in variable quantity, 
longitudinally arranged, an internal extremely delicate lining membrane, and 
an intermediate circular coat, which constituted the principal bulk of the vascular 
parietes, and which, when highly magnified, was found to consist of a single 
layer of muscular fibre-cells, each wound spirally round the internal membrane 
so as to encircle it from one and a half to two and a half times. 

Now when we consider the properties of muscular fibre-cells, which, as is 
shown in the paper referred to, are capable of contracting in the pig’s intestine 
as much as to one-tenth of their length, it is impossible to conceive a more efficient 
mechanism for the constriction of a tube than is provided in these minute 
arteries. On the other hand, the capillaries are totally destitute of any structure 
known to be contractile. The changes of calibre which occur in the vessels 
of the living web are in perfect harmony with this anatomical description ; for 
while the arteries, even to their smallest branches, are sometimes constricted 
to absolute closure, and at other times widely dilated, the capillaries are never 
found to be entirely closed, nor to present any variations in diameter, which are 
not explicable by elasticity of their parietes.’ 


* Printed at p. 15 of this volume. 
* In this respect I merely confirm the observations long since made by Messrs. Pagetand Wharton Jones. 


ON THE EARLY STAGES OF INFLAMMATION 219 


The sketch given below represents the calibre of an artery dividing into 
minute branches, with the capillaries into which they poured their blood. At 
the time when it was drawn, the artery and its branches were in a state of spon- 
taneous contraction, yet the capillaries retained their full average dimensions. 
After a while the artery became so much more contracted as only to admit 
single corpuscles even through the main trunk ; yet still the capillaries fed by it 
did not appear affected in calibre. This is but one example of what I have 
observed times without number. 


= 
ee 

The capillaries, though not contractile, are highly elastic, and by virtue of 
this property are capable of considerable variation in capacity, according to the 
distending force of the current of blood. Figs. 3 and 4 of Plate ITI (see p. 68), 
traced with the camera lucida, show, besides the pigment in two chromatophorous 
cells of the frog’s foot, part of a capillary in nearly extreme conditions in point 
of calibre. In Fig. 3 the vessel is about equal in diameter to the length of a red 
corpuscle, while in Fig. 4 it is so narrow that the corpuscles in it are pinched 
transversely and elongated. When the capillaries are most distended, their 
parietes are much thinner than when shrunk to their smallest dimensions ; 
an estimate may be formed of the difference by comparing the close proximity 
of the corpuscles to the outer bounding line of the vessel in Fig. 3 with the con- 
siderable interval in Fig. 4, that interval representing the apparent thickness 
of the wall of the vessel. It is to be observed that the frog had been killed in 
a manner involving considerable haemorrhage before Fig. 4 was traced, so that 
the capillaries were then little, if at all, distended with blood. The thinness 
of the walls of the capillaries, as compared with the small arteries, is, doubtless, 
calculated to favour the mutual interchanges which must take place between 
the blood in them and the tissues in their vicinity. 

It is believed by some eminent authorities that mutual attractions and 
repulsions subsisting between the nutrient fluid and the tissues among which it 


220 ON THE EARLY STAGES OF INFLAMMATION 


flows, become a source of movement in the blood and assist its flow through 
the capillaries; while others regard the heart as the sole cause of the circulation : 
and the difference of opinion on this fundamental point in physiology involves 
discordance in pathological theory, for some who hold the former view consider 
the changes which occur in the circulation at the commencement of inflamma- 
tion, to be principally owing to modifications of the ‘ vital’ moving force. 
The view that such a cause of movement exists, has been supported partly by 
argument drawn from the phenomena of inflammation: but these, as we shall 
see, require a very different interpretation. It has also been based upon a sup- 
posed analogy between the circulation of the blood in the higher animals and 
certain movements observed to occur without any visible source of mechanical 
power in tubes and cells in the vegetable kingdom, and, as was thought, also 
in some of the lower forms of animal life: but though a resemblance may pro- 
bably exist between some of these and the movements occurring in the processes 
of secretion and absorption and the circulation of nutrient fluid among the 
tissues of intercapillary spaces and non-vascular parts, the progress of modern 
discovery tends to show that the comparison is altogether inapplicable to the 
sanguiniferous system. It would, I think, be out of place to enter fully into 
this discussion on the present occasion, but my own experience with the frog 
leaves no doubt in my mind that in that animal contractions of the heart are 
the only cause of the circulation. I will content myself with mentioning two 
observations bearing upon this question. The first of these has reference to 
certain movements which occur for a considerable time after cessation of the 
heart’s action, and which, though of trivial and uncertain character, have had 
much stress laid upon them in this discussion. I have ascertained by observations 
made in several different cases, that they are produced by occasional spontaneous 
contractions and relaxations of the arteries. These changes in the calibre of 
the vessels continue, even in an amputated limb, for days after severance from 
the body :* I have repeatedly watched them taking place, and seen them give 
rise to the movement of the blood. 

The other fact to which I will allude appears to me to decide of itself the 
question at issue. Having occasion to examine, under chloroform, some very 
small frogs, measuring about an inch from the tip of the nose to the end of the 
coccyx, I found that the blood in the capillaries invariably flowed in a stream 
pulsating synchronously with the beats of the heart, which were visible through 
the parietes of the thorax; and however mildly the anaesthetic was adminis- 


* See Outlines of Pathology and Practice of Medicine, by W. P. Alison, M.D., F.R.S.E., &c., 1884, 
pp. 115 et seq. 

* See the preceding paper on the parts of the Nervous System which regulate the Contracticns of 
the Arteries, p. 27 of this volume. , 


ON THE EARLY STAGES OF INFLAMMATION 22% 


tered, the motion was commonly exceedingly slight between the pulses. Not 
unfrequently, although the arteries remained of full size, the blood moved in 
jerks, with considerable intervals of absolute stillness between the successive 
impulses which the contractions of the heart occasioned ; yet no accumulation 
of corpuscles was produced in the capillaries, however long the animal was kept 
under observation. Had any other cause of motion than the action of the 
heart operated upon the blood, there must have been a continuous flow, however 
much accelerated at each pulse ; for I must add, that there was nothing what- 
ever of recoil after each onward movement, nor anything indicating obstruction 
to the progress of the blood. 

Thus in these cases of intermitting capillary flow, it was matter of direct 
observation that the heart was the sole cause of the blood’s motion; and as 
we know that in an animal under the influence of chloroform the changes of the 
blood from arterial to venous, and vice versa, continue to occur in the systemic 
and pulmonary capillaries, and as we have every reason to believe that the 
processes of nutrition in the different parts of the body go on then as usual, 
these cases appear to prove absolutely that the forces which are concerned in 
the mutual interchanges between the tissues and the nutrient fluid do not cause 
any movement whatever. 

But even supposing that it were admitted, for the sake of argument, that 
the vital affinities do, under ordinary circumstances, cause some movement 
of the blood, but lose that power in an animal under chloroform, such an ad- 
mission would hardly affect the discussion regarding the cause of stagnation 
in inflammation ; for in a frog fully under the influence of the anaesthetic, 
in which, as we have seen, the heart is the only cause of circulation, all the 
phenomena that result from irritation of the web take place precisely in the 
same manner as in one to which the narcotic has not been administered. The 
fact that the heart, even though much enfeebled by chloroform, is capable, 
unaided by any other force, of maintaining the circulation for an indefinite 
period without the occurrence of obstruction in the capillaries, or any undue 
accumulation of corpuscles in them, affords positive proof that any other cause 
of movement which may be conceived to exist when chloroform has not been 
given, must be altogether insignificant, and that the cessation of its operation 
does not give rise to stagnation of the blood. 


1 Dr. Sharpey has for many years alluded in his lectures to the circumstance that, the weaker the 
animal, the more do the effects of the successive cardiac impulses show themselves in the capillaries 
of the webs, as evidence that the action of the heart is sufficient to account for the circulation. He 
also informs me that he has frequently verified the observation of Spallanzani, that in the gills of the 
tadpole the flow of the blood ceases completely in the intervals between the pulses produced by the 
ventricular contractions. 


222 ON THE EARLY STAGES OF INFLAMMATION 


The veins of the frog’s web afford very little evidence of contractility ; 
but a small amount of unstriped muscular tissue, transversely arranged, is 
distinctly to be seen in the larger venous branches; and on one occasion I 
observed a very considerable degree of local contraction, as measured from the 
outer borders of the external coat of a vein running through a small area which 
I had pinched forcibly with forceps. I have also seen one expand on sudden 
dilatation of the arteries of the web, so that its diameter increased from twelve 
to fourteen degrees of a micrometer ; but this is perhaps explicable by elasticity. 

It has been already mentioned that the arteries undergo spontaneous 
variations of calibre. Such changes are constantly going on at varying intervals, 
there being nothing of a rhythmical character about them. A struggle on the 
part of the animal is generally accompanied by a very considerable constriction 
of the arteries, and sometimes by absolute closure of them. The contraction 
usually begins a very short time before the motions of the body, so that the 
struggle can commonly be predicted by the appearance of the vessels; and 
dilatation occurs when the creature becomes quiet. Hence the changes of 
calibre are evidently under the control of the nerves. An account of an inquiry 
into the parts of the nervous system by which this control is exercised, will be 
found at p. 27 of this volume; and from the experiments there recorded, it 
will be seen that either extreme constriction or full dilatation of the arteries 
of the web may be induced at pleasure, by operating upon the spinal cord. 
A very good opportunity is thus afforded for studying the effects produced upon 
the capillary circulation by changes of calibre in the arteries, without employing 
any means acting directly upon the foot. This is a matter of very great impor- 
tance, for applications made to the web for the purpose of inducing alterations 
in the dimensions of the vessels, give rise at the same time to other consequences 
of irritation, which complicate such experiments in a most deceptive manner, 
so as to have misled, as I believe, some of the best observers who have devoted 
attention to this subject. 

The following account embodies the results of numerous observations in 


* Since the reading of this paper I have noticed striking examples of the contractility of the larger 
veins in the higher animals. Thus, on exposing the jugular in a living calf, I have seen a particular 
part of the vessel irritated by the process of dissection shrunk to about a third of its previous calibre. 
In the human subject, too, when amputating lately at the shoulder-joint on account of contusion in- 
flicted by machinery upon a previously healthy limb, I noticed the axillary vein reduced to about half 
its natural calibre at the part where it was divided, which was in the immediate vicinity of the injury. 
I have also had occasion to observe the post mortem contractions of the subcutaneous veins of the sheep’s 
foot, which are carried to such an extent as to reduce the vessels from the size of a crowquil to about 
that of a darning-needle. The minute veins also sometimes exhibit great contractility in the higher 
animals, as in the irregular constrictions often seen in those of the mesentery of the mouse, and in the 
remarkable rhythmical variations in calibre discovered by Mr. Wharton Jones in those of the bat’s 
wing (Philosophical Transactions, 1852). 


ON THE EARLY STAGES OF INFLAMMATION 228 


which this source of fallacy was carefully avoided, the variations in the calibre 
of the vessels being generally either induced by operations on the cord, or else 
such as occurred spontaneously. 

In a perfectly healthy state of the web with the heart beating powerfully, 
when the arteries are of about medium width, the current of blood in them 
is so rapid that the individual corpuscles cannot be discerned ; but in the capil- 
laries, whose aggregate calibre is very much greater than that of the arterial 
trunk which feeds them, the flow is so much slower that they can be pretty 
clearly distinguished. When the arteries are fully dilated, if the heart con- 
tinues to act with the same energy, the blood appears to move as rapidly in 
them as before, though of course in much larger quantity ; while in the capillaries 
the flow is extremely accelerated, so that it becomes as impossible to see the 
blood-corpuscles in them as in the arteries. On the other hand, when the 
arteries are considerably constricted, the blood moves more slowly through the 
capillaries than when the tubes of supply are of medium size, and at the same 
time the narrowed arteries appear to filter the blood more or less of corpuscles, 
which are found in smaller numbers in proportion to the liquor sanguinis in the 
capillaries: and if the constriction of the arteries is sufficiently great, the web 
is rendered quite pale in consequence of the small number of corpuscles in it, 
which nevertheless continue to move among the tortuous capillaries, producing 
in the field of the microscope an appearance something like that of a few flies 
playing about in a room. Finally, if the arteries are completely constricted, 
all appearance of flow in the capillaries vanishes, and the web has a wholly 
exsanguine aspect. Under these circumstances, even the veins, though still of 
large calibre, may contain little besides colourless liquor sanguinis, which has 
continued to ooze through the contracted arteries when the corpuscles have 
been completely arrested ; and so inconspicuous do the veins become in con- 
sequence of this change in the quality of their contents, that it may be extremely 
difficult to distinguish them from other tissues; the appearance of the web 
on superficial observation being as if it possessed no blood-vessels at all. This 
remarkable condition, which, so far as I know, has not been before described, 
may last for several minutes in consequence of irritation of the cord, and in one 
case I observed it occur spontaneously, and continue for five minutes together. 
It appears to be comparable to the dead whiteness of the human fingers when 
benumbed with cold, or the perfect pallor of the cheek in faintness ; while 
blushing is no doubt caused by full dilatation of the arteries. 

Such, according to my experience, are the effects produced upon the circu- 
lation by changes of calibre in the vessels of a perfectly healthy web. The 
arteries regulate by their contractility the amount of blood transmitted in 


224 ON THE EARLY STAGES OF INFLAMMATION 


a given time through the capillaries, but neither full dilatation, extreme con- 
striction, nor any intermediate state of the former is capable fer se of producing 
accumulation of corpuscles in the latter. 


SECTION ITI 
On the Effects of Irritants upon the Circulation. 


It is well known that the application of an irritant substance to the web 
of the frog’s foot is followed by changes of calibre in the blood-vessels, and also 
by an abnormal accumulation within them of the corpuscular elements of the 
blood. The first experiments which I performed upon the frog were directed 
to the solution of the much-debated question, whether or no the latter were 
a mere consequence of the former ; and although it has, I think, been sufficiently 
shown at the conclusion of the last section that such cannot be the case, yet 
it will be well to allude shortly to these experiments on account of their further 
bearing upon the subject of this inquiry. 

It occurred to me that if, instead of the powerful irritants commonly used 
in these investigations, some exceedingly mild stimulant were employed, the 
changes in the calibre of the vessels might perhaps be produced without con- 
comitant alterations of the blood. The material which appeared most suitable 
for this purpose was warm water, which is known to cause, in the human subject, 
increased redness without inflammation of the part to which it is applied. 

Accordingly, in September 1855, I endeavoured to ascertain its effects 
upon the frog. In most of the experiments, the foot of the animal being stretched 
under the microscope upon a glass plate somewhat inclined, so that any fluid 
upon it might run off quickly, an assistant threw a stream of water of known 
temperature upon it by means of a syringe, the eye of the observer being kept 
over the microscope, which was provided with a micrometer in its eyepiece. 
In this way the effects produced by the water could be seen almost immediately 
after it had ceased to play upon the web, and the changes of calibre in any 
artery selected for observation were noted with precision. It was found that 
the result of the warm application was constriction of the arteries to absolute 
closure, generally lasting for several seconds,' and then giving place to dilatation 
beyond their original dimensions, to which they afterwards gradually returned. 


‘ The period of constriction varied much in different instances, and it sometimes passed off (if it 
occurred at all) before it could be observed. It was best marked in a case, in which, the animal being 
very quiet, chloroform was not employed. The anaesthetic appears to impair the functions of the 
spinal cord as a regulator of the calibre of the vessels ; and its administration is generally followed by 
their dilatation. 


ON THE EARLY STAGES OF INFLAMMATION 225 


The dilatation differed in different instances, being generally more decided and 
more permanent when the water was hotter and longer applied.t_ In one case, 
water at 100° thrown upon the web for a brief period caused constriction for 
a few seconds in the artery under observation, followed by dilatation. While the 
vessels were still above their usual calibre, more water of the same temperature 
was applied as before, and again induced contraction followed by abnormal 
dilatation, which was again made to give place toconstriction by a third similar 
application : the experiments were repeated within a few seconds of each other. 

When water not higher in temperature than from 110° to 140° was thrown 
for not longer than a second or two upon a perfectly healthy web, the changes 
above described in the diameter of the arteries produced effects upon the flow 
of blood through the capillaries, precisely similar to those mentioned at the 
conclusion of the last section. Thus in one such case the constriction of an 
artery lasted for several seconds, and was in the first instance so tight as to 
prevent any flow in the field of capillaries supplied by it ; then relaxing slightly, 
it allowed single corpuscles to pass along it with great difficulty, so that the 
blood became almost entirely filtered of its particles, and at the same time the 
force of the heart being to a great extent taken off from the elastic capillaries, 
liquor sanguinis almost destitute of corpuscles flowed in slow pulsating streams 
along the veins: finally, the dilatation becoming complete, blood of ordinary 
appearance rushed through with great rapidity. 

If, however, such experiments had been several times repeated upon the 
same foot, and more especially if the warm water had acted for longer periods, 
another class of symptoms began to show themselves ; the corpuscles passing 
on less freely than the liquor sanguinis through the capillaries, and lagging 
behind so as to accumulate in abnormal proportion to the plasma, and stagnating 
completely when the force of the heart was partially taken off through con- 
traction of the arteries, though passing on again when the vessels dilated.” 

Thus in one case an artery under observation measuring 2° (degrees of the 


* Water of the temperature of the room applied in the same way after warm water had been several 
times employed, caused complete constriction of the arteries, lasting for several seconds ; but the sub- 
sequent dilatation was very little if at all beyond the normal calibre. 

> This effect of arterial contraction in producing accumulation and stagnation of corpuscles in the 
capillaries has been described by Mr. Wharton Jones as occurring in a state of health (see Guy's Hospital 
Reports, loc. cit.). The reason of this I believe to have been, that much greater care than is generally 
supposed is required in order to avoid any irritation whatever of the delicate webs. The vicinity of the 
warm hand is particularly apt to produce this effect ; and I have known it, when continued for a quarter 
of an hour, cause complete stagnation of the blood throughout the webs, while a very much shorter 
period is sufficient to induce a decidedly abnormal condition. I have myself only become fully aware 
of the great susceptibility of the foot of the frog to injury from warmth since the reading of this paper. 
An unhealthy state of the webs is indicated to the naked eye by conspicuousness of the blood-vessels. 
In perfect health they are quite invisible without the microscope, and in all cases the appearance of any 
vessel as a distinct red streak is pretty sure indication of a certain amount of irritation. 

LISTER I Q 


226 ON THE EARLY STAGES OF INFLAMMATION 


micrometer), the blood was flowing in all the capillaries supplied by it, though 
containing a very abnormal amount of corpuscles. After a few minutes, the 
vessel contracted spontaneously to 14°, and though this was only about a medium 
width, the flow of the blood became much retarded in the capillaries, and in one 
of them ceased almost entirely. Water of 115° Fahr. being then thrown upon 
the web, the calibre of the artery was raised to above 2°, and the flow was re- 
sumed in all the capillaries. A few minutes later the vessel again contracted 
spontaneously to 14°, when stagnation of the blood became nearly complete 
in a few of the capillaries. Water at 120° was then applied and caused con- 
striction to a further degree, followed by dilatation to above 2°: during the 
constriction, the blood scarcely moved at all in the capillaries, but on the occur- 
rence of the dilatation it again flowed in all of them. 

If the applications were still further continued, the red discs became more 
and more closely packed, till at last they were crammed together so as to pro- 
duce a uniform crimson mass, unaffected by the heart even in the widest state 
of the arteries. 

It was perfectly clear that in these experiments the stagnation of the blood 
depended on something more than mere contraction of the arteries; and it 
also appeared impossible to account for it satisfactorily as a result of their 
dilatation. That inflammatory stasis might occur independently of alteration 
in the calibre of the vessels, was also shown by an experiment with capsicum 
made at this period. A morsel of this substance having been placed upon the 
middle of a web in which the circulation was going on in perfect health and 
with unusual rapidity, the effect was great accumulation of corpuscles in two 
or three capillaries for a very short distance round the spot where the capsicum 
lay, unaccompanied by any change in the vascular dimensions. 

Chloroform proved to be an agent which very readily induced stagnation 
when locally appled ; and when it was administered in the usual way by inhala- 
tion for the purpose of performing experiments with warm water, it was found 
necessary to protect the webs carefully from its vapour, which otherwise pro- 
duced the same appearances of congestion as the hot application. In one 
instance in which a small quantity of the liquid had been applied to the web, 
I saw the red corpuscles adhering to one another by their flat surfaces, in a 
manner not seen in the healthy condition, and exactly as described by Mr. 
Wharton Jones to take place after the application of a strong solution of salt ; 
but from the very slight tendency of chloroform to mix with water, it was 1m- 
possible to believe that it had operated by way of exosmose, as was supposed 
by the authority just named to be the case with the saline solution. 


» It was believed that the solution of salt abstracted water from the blood as it flowed through 


ON THE EARLY STAGES OF INFLAMMATION 227 


From the facts above mentioned, I became convinced that no satisfactory 
explanation had as yet been given of the obstruction experienced by the blood- 
corpuscles in the vessels of an inflamed part, and in September 1856, I again 
continued the investigation. Mustard being admitted to produce inflammation 
in any part of the human body to which it is applied, and also not appearing 
likely to act by way of exosmose, I selected it as a suitable irritant, and in order 
to study its effects accurately, placed a small portion of its moistened flour, 
about a line in diameter, upon the middle of the web of a large frog under chloro- 
form. After a while, thinking that I saw stagnation in a capillary just at the 
margin of the mustard, I removed the latter with a camel’s-hair brush, and 
was surprised to find that throughout the whole area on which it had lain, the 
capillaries were crammed with either stagnant or very slowly moving red cor- 
puscles. The limits of the part so affected corresponded exactly with the extent 
of the application of the mustard, although the capillaries of adjoining parts 
were fed and drained by the same arteries and veins, 

On the 3rd of October I made another similar experiment, selecting a part of 
the web where a considerable artery divided into small branches. Before applying 
the irritant, I had ascertained that the artery running through the area measured 
64° of an eyepiece-micrometer,! while a large vein near it had a diameter of 12°. 
About half a minute after the application of the mustard, when I first looked 
through the microscope, the arteries of the web generally were much dilated, 
and the flow, which had before been somewhat languid, was rapid in all its 


the capillaries, and that the liquor sanguinis being consequently inspissated, the red corpuscles assumed 
an abnormal tendency to aggregate together (see Guy’s Hospital Reports, loc. cit., p. 40). This view 
has been more recently advocated by a German writer, Fr. Schuler of Glarus (Wiirzburg Verhandlungen, 
1854), with a very elaborate series of difficult experiments. One of these, however, seems almost con- 
clusive against his theory. Having injected a solution of prussiate of potash into the veins of a frog, 
he applied sulphate of iron to the webs, but found that very little blue colour was produced unézl the 
epidermis of the web was scraped away, when it showed itself distinctly. Considering how delicate a test 
prussian blue is of the presence of a mixture of the two salts, this result seems to show that there is far 
from being the same tendency to mutual interchange between the blood in the capillaries and fluids in 
contact with the surface of the web, as there would be if the intervening material were dead animal 
membrane of the same tenuity. Were the disposition to exosmosis and endosmosis such as is assumed 
in the above explanation of stasis from a solution of salt, it would be impossible for the animal to live 
long either in water or on dry earth. In the former case the blood would soon become diluted from 
imbibition, and in the latter inspissated from evaporation. But it is well known that frogs will live for 
months in water without food, and I have kept them for weeks together upon dry earth at a temperature 
of about 60° Fahr., and on removing from the webs a layer of dust and exfoliated epidermis, found the 
circulation perfectly healthy. Since the reading of this paper, I have seen a remarkable example of 
the power of the tissues of the webs to resist imbibition of water in an amputated limb with the blood 
retained in the vessels by a ligature. Though it was kept in wet lint, the blood in the vessels showed 
no indication of admixture of water till the tenth day, and then only in those parts of the web in which 
the arteries and pigment-cells gave evidence that they had lost their vitality. For further particulars 
regarding this experiment see pp. 39 and 63 of this volume. 

+ The micrometer used on this occasion was differently graduated from that employed in the warm- 
water experiments. 


Q 2 


228 ON THE EARLY STAGES OF INFLAMMATION 


capillaries. The opacity of the mustard prevented the vessels beneath it from 
being observed, but at a short distance from its edge the artery measured I0° 
and the vein 14°. In a few minutes the capillaries seen beneath the extreme 
margin of the mustard, which was slightly transparent, were observed to be of 
crimson colour, in consequence of their containing closely crammed corpuscles, 
some of which were still moving, while others were motionless. On the applica- 
tion of a higher power, the continuations of these capillaries immediately exterior 
to the mustard showed, many of them, red corpuscles sticking to their walls, 
and more or less obstructing the progress of the blood through them. 

In the accompanying sketch of the 
vessels at one part, together with those 
corpuscles which were motionless in them, 
M represents the edge of the mustard, aa 
capillary partly overlaid by the mustard and 
crammed with stagnant corpuscles, ba capil- 
lary with red discs adhering to its internal 
surface, but still transmitting blood, while 
further from the mustard all the corpuscles 
were in motion, and consequently none 
appear in the drawing ; c was a rouleau of 
red corpuscles projecting from a stagnant 
mass into the vein V, through which the 
blood was flowing rapidly ; yet the rouleau, 
though its free end was moved to and fro 
by the current, was prevented by the mutual 
adhesiveness of its corpuscles from being 
broken up or detached. Thus it was evident 

\ that in the capillaries of the space covered 

by the mustard, the red corpuscles had an 

abnormal tendency to adhere both to the walls of the vessels and to one another, 
and were on this account accumulating and sticking within them, while almost 
immediately outside the mustard, the blood in the capillaries presented the 
same appearance as in other parts of the web. This effect was independent of 
changes in the calibre of the vessels, for any results of alteration in the size 
of the artery under the mustard must have been shared by the surrounding 
capillaries, which also derived their blood chiefly from it ; and that the vesse 
was dilated to the same degree there as elsewhere, was shown by the fact, that 
its branches continued throughout the experiment to transmit full streams of 
blood after emerging from beneath the opaque mass. I also measured some 


ON THE EAREY SIAGES OF INFLAMMATION 229 


capillaries by micrometer before the application of the mustard, and again after 
it had caused stagnation in them, and found that their dimensions remained 
the same.? 

The precise limitation of the effect produced upon the blood in these two 
experiments to the area covered by the mustard, showed that it was the result 
of a direct action of the irritant either upon the blood that flowed beneath it, 
or upon the tissues of the part of the web on which it lay, the blood being in 
the latter case affected secondarily. I made several experiments to determine 
whether the adhesiveness of the corpuscles in blood out of the body was increased 
by contact with or vicinity to mustard, placing minute portions of it between 
plates of glass, and shedding a drop of blood from a frog, so that it might run 
in between the plates, and watching the result. I could, however, detect no 
evidence of such change in the corpuscles as I was seeking ; whence I inferred 
that the blood had been only affected secondarily to the tissues in the two 
mustard experiments. 

A careful study of the effects produced by the local application of chloro- 
form to the web, confirmed in every respect the conclusions previously arrived 
at. If, while the eye of the observer is over the microscope, a minute drop 
of this liquid is placed with a camel’s-hair brush upon the part in the field of 
view, it evaporates in perhaps two or three seconds ; and if the web be dry, the 
time of its disappearance can be distinctly seen. Yet though it has so short 
a time to act, it produces so powerful an effect upon the part, that the red cor- 
puscles immediately experience obstruction to their progress, and move too 
slowly in abnormal numbers through the capillaries, which perhaps become 
entirely clogged with them; the arteries meanwhile being in the state best 
adapted for easy transmission of the blood, i.e. full dilatation. In one such 
experiment I saw a few corpuscles sticking together in a capillary and moving 
with difficulty, from evident tendency to adhere to its parietes, their number 
gradually becoming augmented by the adhesion of others that followed, till 
the mass grew so large as to fill the vessel for some distance, when it finally 
stopped. In another case, the circulation being perfectly natural in the web, 


’ The increased pressure upon the blood in the capillaries, resulting from obstruction to the progress 
of the corpuscles, leads to the distension of their elastic parietes up to a certain point, but, generally 
speaking, not further. In the present case, before the application of the mustard, the web, irritated 
probably by the vapour of the chloroform, was affected with a slight congestive tendency, far short 
of that which induces stagnation, but yet sufficient to give rise to full distension of the capillaries. When 
the web has been perfectly healthy to begin with, I have seen a marked increase of calibre in the capil- 
laries on the occurrence of stagnation in them. This I noticed particularly in a case in which caustic 
ammonia was the irritant employed. I would remark, however, that the eye is apt to be much deceived 
on this point unless the micrometer is used. Those vessels which are crammed with corpuscles, being 
of dark crimson colour, look at first sight larger than others, really of the same size, which contain the 
normal ‘proportion of liquor sanguinis, and are therefore of pale tint. 


230 ON THE EARLY STAGES OF INFLAMMATION 


and the corpuscles moving on at slight intervals with no tendency to adhere, 
on a drop of chloroform being applied, I saw the very same corpuscles instantly 
become checked in their progress by sticking to each other and to the capillary 
walls, and move on slowly in masses with considerable intervals. Thus the 
nature of the effect produced upon the red corpuscles of the blood when chloro- 
form is applied to the web is the same as that caused by mustard, viz. an abnor- 
mal degree of adhesiveness ; whereas the earliest evidence of the direct action 
of chloroform on blood out of the body is the loss of the adhesive property of 
the red discs, as has been mentioned in Section I.1. That the effect on the blood 
within the vessels of a part inflamed by chloroform is secondary to a change 
in the tissues is further proved by the circumstance, that abnormal accumulation 
of slowly moving corpuscles may last for hours together without stagnation, 
as a consequence of the application of this irritant for an extremely brief period.’ 
Long after all the blood which could possibly have been directly acted on by 
the chloroform has left the vessels, successive fresh portions continue to experi- 
ence precisely similar changes in passing through the irritated area. 

Heat produces similar effects. If the foot of a frog which is under the 
influence of chloroform be covered entirely with wet lint, except a small area of 
one of the webs, and a red-hot cautery iron be held for a few seconds about 
half an inch above the exposed part, inflammation will be excited in the area 
in proportion to the time of the action of the dry heat upon it ; but on removal 
of the lint, the circulation will be found perfectly healthy in the surrounding 
parts. In the severer cases stagnation is universal in the exposed area, and 
the epidermis becomes eventually raised by the exudation of serum beneath it ; 
but in milder instances nothing more than accumulation of slowly moving 
corpuscles is produced, and I have observed this state of the part to continue 
for hours after the heat was applied. Here again the effect on the blood was 
obviously not due to the direct action of the heat upon it, but to some changes 
which it had effected in the tissues of the part on which it had acted. 

Evidence of the same kind, but still more conclusive, is derived from the 
effects of mechanical irritation, where the agency is free from all objection of 
possible chemical action on the blood. The method adopted was that of com- 
pressing a small part of the middle of the web between little pads of soft material 
attached to the ends of the blades of a pair of surgical dressing forceps, by which 

* SE€ Pp. 215. 

* The gradual supervention of the effects of irritation upon the blood may be watched very con- 
veniently by arranging a piece of lint soaked in chloroform, so that the vapour may play upon the web 
while the eye of the observer is over the microscope. If the chloroform be removed when the tendency 


to accumulation of corpuscles exists in a very slight degree, restoration to health will occur within a few 
minutes. 


ON THE EARLY STAGES OF INFLAMMATION 22% 


the degree of pressure could be regulated at will. The results of this treatment 
were identical with those of heat, as just described. If the pressure was not 
made too severe, no mechanical obstruction was produced in the vessels, which 
nevertheless became loaded with slowly moving or stagnant corpuscles ; and 
on one occasion I observed the capillaries of an area which had been pinched, 
still transmitting languid streams of blood containing great excess of corpuscles 
several days after the injury had been inflicted, while in the surrounding parts 
the circulation continued perfectly healthy. Mechanical violence, like heat, 
chloroform, and mustard, had effected an alteration in the tissues on which it 
operated, in consequence of which the blood in their vicinity assumed abnormal 
characters ; and many other facts of similar nature might be added, if necessary, 
to show that this is the course always followed when accumulation of corpuscles 
in the vessels is induced by the action of irritants. 

In discussions regarding the causes of the phenomena of inflammation seen 
in the frog’s web, the great difficulty has hitherto been to account for the puzzling 
fact, that while the arteries still retain that state of enlarged calibre which is 
best adapted for easy transmission of the blood, its accelerated movement comes 
to give place to unnatural retardation and ultimate stagnation. Accordingly, 
various theories, mechanical, chemical, and vital, have been proposed? to explain 
the transition from ‘ determination of blood’, as the condition of dilatation 
of the arteries with increased flow through the capillaries has been termed, to 
inflammatory congestion, as the accumulation of corpuscles in the vessels may 
perhaps be most fitly designated. But the second simple experiment with 
mustard, to which I would again direct the attention of the reader, proves in 
a very beautiful manner that these two results of irritation are totally distinct 
in nature and independent in cause. The dilatation of the arteries, it will be 
remembered, affected not only the part on which the mustard lay, but also all 
the rest of the web, showing that it was developed indirectly through the medium 
of the nervous system; whereas the accumulation of the blood-corpuscles in 
the vessels below the mustard was, as we have seen, the result of the direct 
action of the irritant upon the tissues. The arterial dilatation in the web 
generally led to no changes in the quality of the blood, which, though the experi- 
ment was continued for some hours, retained to the last its natural characters, 
just as would have been the case had the enlargement of the vessels depended 
on an operation performed upon the spinal cord. The accumulation of cor- 

1 See Pathology and Practice of Medicine, by W. P. Alison, M.D., F.R.S.E. ; Principles of Medicine, 
by C. J. B. Williams, M.D., F.R.S.; Lectures on Surgical Pathology, by James Paget, F.R.S. ; ‘ Observations 
on the State of the Blood and the Blood-vessels in Inflammation,’ by T. Wharton Jones, F.R.S.: Guy's 


Hospital Reports, vol. viii; Clinical Lectures, by J. H. Bennett, M.D., F.R.S.E.; also Professor Henle, 
as quoted by Wharton Jones, op. cit. 


232 ON THE EARLY STAGES OF INFLAMMATION 


puscles, on the other hand, implied an alteration in the properties of the blood, 
viz. an abnormal adhesiveness in the red discs. Determination of blood is thus 
a purely functional phenomenon, and, like a blush upon the cheek, becomes 
obliterated after death by the post mortem contractions of the vessels: inflam- 
matory congestion, on the contrary, is the first evidence of organic lesion, and 
declares itself as distinctly in the dead as in the living, being the most important 
if not the only sign of the early stages of inflammation discoverable on dissection," 
as for instance in the case of incipient meningitis mentioned in the Introduction 
to this paper. 

Although determination of blood, as met with in the frog, is thus entirely 
independent of inflammatory congestion, yet it is of great interest with refer- 
ence to human inflammation. Dilatation of the arteries is now generally 
admitted to be the result of the relaxation of their muscular fibres ; and that 
it is a purely passive phenomenon, seems to be absolutely demonstrated by 
the fact which I have pointed out elsewhere,? that after the vessels have been 
liberated from the control of the nervous system by removal of the spinal cord, 
they dilate fully if the heart continues to act sufficiently powerfully to distend 
them with blood, but not otherwise. Recent physiological discovery has shown 
that the arteries are not singular in being thrown into a state of muscular relaxa- 
tion through irritation of the parts of the nervous system connected with them, 
the same being the case with the heart, the intestines, and apparently also with 
other hollow viscera. In a ‘Preliminary Account of an Inquiry into the Func- 
tions of the Visceral Nerves’, published in the Proceedings of this Society,’ I have 
given some notice of experiments which seem to show that in the case of the 
viscera alluded to, the state of relaxation under such circumstances is the result 
of the more energetic operation of nerves, which, when working more mildly, 
increase the muscular action of the same organs; the functions of the ganglia 
specially concerned in regulating the movements of the viscera being exalted 
by gentle stimulation on the part of the afferent nerves connected with them, 
but depressed by stronger excitation. In that paper the opinion was expressed, 
that the same explanation probably applies to the relaxation of the arteries, 


* Since the reading of the paper, I have pointed out that, in consequence of the persistent fluidity 
of the blood which continues in the smaller vessels for days after death, the red corpuscles have time 
to gravitate into dependent parts, and thus give rise to that appearance of post mortem congestion 
which more or less closely simulates to the naked eye what would have resulted from inflammation during 
life. See a paper by the author ‘On Spontaneous Gangrene from Arteritis and the Causes of Coagulation 


ot the Blood in Diseases of the Blood-vessels’, Edinb. Med. Journal, April 1858 (page 69 of this volume). 
* See pp. 27 et seq. of this volume. 
* Page 87 of this volume. The paper here referred to was written subsequently to the reading 


of the manuscript of this essay, and this was also the case with the remarks in the text on determination 
of blood. 


ON: THE DARL Y STAGES OF INFLAMMATION 233 


in consequence of nervous irritation ; the general impression conveyed by the 
experiments with warm water above related being that arterial contraction 
was most apt to show itself when the degree of irritation was least, while dilata- 
tion was most marked when the stimulus was strongest. I have lately seen 
a Striking illustration of this principle in a very simple experiment, which I was 
induced to make in consequence of reading a paper recently published by a 
French author, M. J. Marey.’ If a blunt-pointed instrument, such as the end 
of a pair of dissecting forceps, is drawn with gentle pressure along the back of 
the hand while it is in a state of moderate redness, the blood being driven out 
of the vessels, a pale streak results, which immediately disappears, in conse- 
quence of the return of the blood into the part. In a few seconds, however, 
a pale stripe, towards a quarter of an inch in breadth, becomes developed at 
each side of the line along which the instrument passed, that line having now 
assumed a red colour, if the pressure employed was at all forcible. This is 
M. Marey’s experiment ; and there can be no doubt that his interpretation 
of the secondary paleness is correct, viz. that it depends on reflex arterial con- 
traction. The red line, when it occurs, is evidently due to the direct action 
of the pressure upon the tissues, being, as M. Marey correctly states, exactly 
of the same breadth as the instrument used. But I find that if the pressure be 
made with considerably greater force, so as to be positively painful, while the 
first white streak appears as before in consequence of the blood being dispelled 
from the vessels, the secondary paleness does not occur, but, on the contrary, 
a patch of the adjacent skin, extending for perhaps half an inch on each side, 
assumes abnormal redness, which lasts for a longer time than the paleness to 
which the other experiment gives rise. Here, the irritation being severe, the 
blood vessels are thrown through the medium of the nervous system into a state 
of muscular relaxation, instead of the contraction which is induced by a more 
gentle application of the same stimulus. 

To return to the consideration of inflammatory congestion. Further light 
was thrown upon the condition of the blood in the vessels of an irritated part 
by a series of observations made when the circulation had been arrested by 
amputation of the limb, or by a ligature round the thigh. This field of inquiry 
was unexpectedly opened during the course of an experiment made with a view 
to ascertaining the effects produced by an irritant upon the pigmentary system 
independently of the circulation, as will be described in the next section. On 
the 13th of October, 1856, a frog having been killed by destruction of the brain, 


1 Recherches Hydvauliques sur la Circulation du Sang, par M. J. Marey. The separate copy of this 
paper, sent me by the author, does not contain any mention of the Journal in which it was published, 
so that I am unable to give proper reference to it. 


234 ON THE EARLY STAGES OF INFLAMMATION 


the soft parts of one of the thighs were divided to the bone, and a small 
piece of mustard was placed on one of the webs of that foot. An hour after- 
wards, on removing the mustard, I saw to my great surprise that the small 
area on which it had lain was red to the naked eye, and that its capillaries, 
examined microscopically, contained abundance of closely packed corpuscles, 
while in surrounding parts the blood was in the same condition as before 
the experiment, viz. of pretty healthy aspect. In other words, well-marked 
inflammatory congestion had been produced by the mustard, and I after- 
wards found that the same thing occurred in a limb completely severed 
from the body.! 

This fact of course completely eliminated variations in the calibre of the 
vessels and consequent changes in the circulation from among the causes of 
congestion, and demonstrated conclusively its independence of the central 
organs of the nervous system. Further, it presented a very good opportunity 
for studying the state of the blood in healthy and inflamed parts, unaccom- 
panied by the effects of rapid movement. In subsequent similar experiments, 
it was found that the corpuscles were not brought to the irritated area by any- 
thing that indicated a mutual attraction between the former and the latter, 
but were simply carried along by slight accidental movements of the blood, 
such as are caused by post mortem contractions of the arteries, and instead 
of moving with facility, as in other parts, stuck when they arrived in the vessels 
of the area, in consequence of undue adhesiveness. The accumulation of the 
corpuscles was never to such an extent as in cases in which the heart was driving 
the blood through the part, but it affected the arterial and venous branches as 
well as the capillaries. Thus, if a large vein happened to run through the spot 
upon which the mustard was placed, it became in time choked with a crimson 
mass of corpuscles in that part of its extent which lay beneath the mustard ; 
but immediately beyond, in both directions, the blood in it contained no more 
than the usual proportion of corpuscles, or sometimes considerably less; and 
these moved freely to and fro when the web was touched, whereas those within 
the area remained fixed. This proved that the cause of the accumulation of the 
corpuscles did not reside specially in the capillaries, and also showed distinctly 
that it could not be explained by mere abnormal adhesiveness of the vascular 
parietes, which was, I understand, the view entertained by the late Dr. Marshall 
Hall ; for supposing the walls of the vessels to experience such a change, which 


* Mr. Paget, to whom I mentioned this experiment, has informed me that the fact that stasis may 
be induced by application of irritant substances to the frog’s foot after the arrest of the circulation by 
ligature of the thigh, had been previously discovered by Dr. H. Weber of Giessen (Miiller’s Archiv. 
1852), and that Schuler of Glarus had afterwards ascertained that the same thing occurs in an amputated 
limb (vide Wurzburg Verhandlungen,1854). 


ON THE BARLY STAGES OF INFLAMMATION 235 


~ 


seems by no means improbable, this could only lead to encrusting of the lining 
membrane of such a vein with adhering corpuscles, and not to the occupation 
of its whole calibre by them, as took place in these cases, unless the corpuscles 
were themselves also abnormally adhesive. 

Another important fact which was brought out by this class of experiments 
is, that mere quiescence of the blood in the vessels of a healthy part fails to 
induce aggregation of the red corpuscles, such as occurs in blood outside the 
body. In the parts which had not been subjected to irritation, the corpuscles 
exhibited no trace of adhesiveness ; and though completely at rest, they were 
nowhere to be seen grouped together, surface to surface, although in the larger 
vessels there was abundant space for the occurrence of this phenomenon, which 
invariably presents itself in freshly drawn frog’s blood examined between plates 
of glass in a sufficiently thick film. On one occasion, when examining the tissues 
of the web of a frog under chloroform, the limb being kept steady by a string 
tied tightly round the thigh, so as completely to arrest the circulation, I was 
particularly struck with the total absence of adhesiveness in the red corpuscles ; 
so much so, that, as the foot had been kept moist without circulation for about 
three hours, I suspected that it must have imbibed water, which, when mixed 
with blood outside the body, destroys altogether the adhesiveness of the red 
corpuscles. This, however, proved to be a mistake; for, having occasion 
to administer more chloroform, I applied it on a piece of lint of considerable 
size without taking the usual precaution of protecting the foot from the vapour, 
and left it so for about a quarter of an hour. On re-examination of the web, the 
red corpuscles were found to possess much mutual adhesiveness, and in the larger 
vessels were grouped together into masses, with considerable spaces of clear 
liquor sanguinis, just as in the best-marked forms of aggregation in frog’s blood 
outside the body. One of these masses was drawn by camera lucida, and is 
represented in the sketch at page 213, along with the outline of the vessel in 
which it lay. I afterwards purposely induced a similar change in the blood 
within the vessels of an amputated limb by means of mustard.!. Having ascer- 
tained that the red corpuscles, though they had been long at rest, were perfectly 
free from the slightest tendency to aggregation, I suspended, at a little distance 
from the web, a piece of lint smeared with freshly prepared mustard, so that 
the pungent vapour of the volatile oil might play upon it; and left it so for 
about a quarter of an hour, when I found the red discs aggregated, as usually 
seen in frog’s blood outside the body. I then shed some blood from the other 
leg between two plates of glass, and on carefully sketching and comparing the 
groups of corpuscles in this specimen and those within the vessels of the irritated 


1 This experiment was performed subsequently to the reading of the paper. 


236 ON THE EARLY STAGES OF INFLAMMATION 


webs, found that their characters were precisely similar.1. These are examples 
of what very numerous observations have tended to establish, namely, that 
on the one hand the red corpuscles in the vessels of a perfectly healthy part 
are free from adhesiveness ; and on the other hand, the adhesiveness which they 
acquire in inflammatory congestion, though varying in proportion to the degree 
of irritation, is never greater than occurs in the blood of a healthy part when 
withdrawn from the body. 

These conclusions, if correct, represent cardinal truths, both in physiology 
and pathology, implying relations of the tissues to the blood both in health 
and in disease, such as have never before been demonstrated, or, I believe, even 
suspected. I was therefore anxious to submit them to further test, particularly 
as it is by no means easy to estimate the precise degree of adhesiveness possessed 
by the red corpuscles within the vessels ; and it occurred to me that one means 
of doing this would be to compare specimens of blood shed from inflamed and 
healthy parts of the same individual; for if my deductions were sound, the 
adhesiveness of the red corpuscles ought to be neither more nor less in the one 
case than in the other. 

With this view I made the following experiments. Having carefully 
examined the blood of a large frog, drawn from a subcutaneous vein of the 
abdomen, so as to become quite familar with the appearance of its corpuscles, 
I applied mustard to the whole surface of one foot till inflammatory congestion 
had been fully developed in it, and then, amputating both feet at the ankle- 
joint, squeezed out blood from each upon a glass plate, and carefully examined 
both specimens, without being able to detect the slightest difference between 
them. The other experiments with this object were performed on the human 
subject. In one of these I applied a portion of moistened mustard to the dorsal 
aspect of the last phalanx of one of my fingers, and retained it there for five 
hours, with the exception of occasional removal for the purpose of drawing 
blood for examination. By the conclusion of the time mentioned, the skin on 
which the mustard had been placed was in a very decided state of inflammation, 
being red, swollen, and painful, and the redness at one spot disappearing imper- 
fectly on pressure, and returning languidly after its removal. A very minute 
drop of blood drawn with a fine needle from the surface of the most inflamed 
part was then compared with a drop of similar size from another finger, but no 
difference could be detected between them, nor had any been observed in pre- 


* In performing experiments upon a foot in which the circulation has been arrested, it is important 
to guard against a deception apt to arise from the direct action of an irritant upon the blood in the vessels. 
Thus, if a drop of chloroform of considerable size be applied to a web under those circumstances, it will 
soak in and produce its chemical effects upon the blood, the earliest of which is complete abolition of 
adhesiveness in the corpuscles. 


ON THE EARLY STAGES OF INFLAMMATION 237 


vious similar comparisons. On another occasion, a friend of mine suffering 
from intense inflammation of the back of the hand, in consequence of the irrita- 
tion of offensive pus, permitted me to take blood with a needle from the most 
severely affected part, and also from one of the fingers, which was healthy. 
I compared drops from the two sources several times very carefully with each 
other by means of the microscope, but could discover no difference between 
them in the adhesiveness of their corpuscles ; as indicated by the time of forma- 
tion of the rouleaux, their mode of grouping, and the tenacity with which the 
discs composing them adhered when they were stretched. The results of these 
experiments appear decidedly confirmatory of the conclusion with reference to 
which they were instituted. 

No mention has been hitherto made of the appearance presented by the 
colourless corpuscles in an irritated part. It is well known that their numbers, 
in proportion to the red ones, vary very much in different frogs, and it so hap- 
pened that in the two on which the first mustard experiments were performed 
they showed themselves but little; nor are they at all conspicuous when the 
circulation has been arrested by ligature ; but in most cases in which irrita- 
tion is applied to the web while the blood is circulating through it, one of the 
earliest abnormal appearances is that of white corpuscles adhering in large 
numbers to the walls of arteries, capillaries, and veins, as first described and 
accurately figured by Dr. Williams.t. This remarkable phenomenon, though of 
itself clear proof of an alteration in the properties of the blood in an irritated 
part, has, strangely enough, attracted little attention from other observers. 
It is evidently analogous to the change which the red discs experience under 
similar circumstances. I find that the account commonly given of the white 
corpuscles in circulation in the vessels of the frog’s web, viz. that they may be 
seen rolling slowly along the walls of the arteries and veins, and sometimes 
sticking to them, though intended to apply to the state of health,” really describes 
a condition of a slight amount of irritation, such as is exceedingly apt to be 
induced by a variety of causes.* In perfect health the colourless corpuscles 

* Vide op. cit. 

* Mr. Wharton Jones, in describing the healthy circulation in the bat’s wing, speaks of the colour- 
less corpuscles as ‘ rolling or sliding sluggishly along the walls of the vessels’, ‘ both in arteries and 
veins.’ He also describes, in the following passage, increased adhesiveness as resulting from irritation. 
“Towards the end of a protracted sitting, after the web had been much irritated, I have seen, in the 
venous radicles especially, colourless corpuscles accumulated in great numbers, as we so often see them 
in the frog,’ But no stress is laid on this fact as bearing upon the nature of inflammation (see ‘ Observa- 
tions on the State of the Blood and the Blood-vessels in Inflammation,’ by T. Wharton Jones, F.R.S., 
Medico-Chirurgical Tvansactions, vol. xxxvi, 1853). Dr. Williams, supposing that the white corpuscles 
were always adhesive within the vessels in health, was led to attribute their abnormal accumulation in 
an irritated part to local fresh formation of those bodies (vide op. cit.). 


* It has been mentioned in the note to p. 225, that this effect is peculiarly Hable to be produced 
in consequence of the vicinity of the warm hand. 


238 ON THE EARLY STAGES OF INFLAMMATION 


are as free from adhesiveness within the vessels as the red discs, but like them 
assume that property in a degree proportionate to the amount of irritation to 
which the part has been subjected. When the irritation has been very slight, 
the white corpuscles, which are susceptible of much greater adhesiveness than 
the red (as we learn from examining blood outside the body?), acquire some 
tendency to stick to the vascular parietes, while the red discs still move on in 
a manner generally regarded as consistent with health, though really lagging 
slightly behind the liquor sanguinis, and consequently presenting themselves 
in somewhat abnormal proportion. I have often observed the complete absence 
of adhesiveness of the white corpuscles within the vessels in health, and have. 
also watched them gradually assume a tendency to adhere, in consequence of 
repeated mild applications of chloroform to a web in which they previously 
exhibited no such disposition whatever. As the irritation increases, the vessels 
become crusted with them often to a remarkable degree, and occasionally large, 
colourless, agglomerated masses of them, just such as are seen in blood drawn 
from the body, may be observed to roll along the large veins among the slowly 
moving and very numerous red discs. I once watched the formation of one 
of these masses? as a delta-like accumulation at the place where a considerable 
venous branch opened into a main trunk, the calibre of which was nearly 
entirely occupied by it before it was swept away by the current. As a general 
rule, the white corpuscles when adhering do not arrest the progress of the red 
ones, which are often seen to pass through very small intervals among the 
colourless masses ; not unfrequently, however, red corpuscles are stopped in 
their course and adhere among the white ones, and sometimes, especially in 
young frogs, capillaries become obstructed throughout their entire length by 
white corpuscles alone, and when this is the case, they are apt to escape notice 
from the inconspicuous character of their contents. 

The adhesiveness of the white corpuscles, as of the red ones, is limited to 
the part irritated. A very good example of this presented itself on one occasion 
when a minute drop of chloroform was applied to a small part of a healthy web 
so as to induce full dilatation of the arteries and great excess of corpuscles, but 
without absolute stagnation. It happened that the part affected was supplied 
with blood by the branches coming from one side of a principal artery ; the 
main trunk being seated just about the limit between the irritated area and 
the healthy region, the adjacent part of which received supply from the branches 
of the vessel on the other side. The latter showed no appearance of adhering 
white corpuscles, nor did the capillaries which were fed by them; but those 


UOC, pe ide 
* This observation was made subsequently to the reading of the paper. 


ON THE EARLY STAGES OF INFLAMMATION 239 


of the irritated part, though springing from the same trunk, were remarkably 
encrusted with them from their origin to their minutest ramifications within 
the area, while the capillaries and veins in the same part were similarly affected. 
This striking appearance continued for hours after the chloroform had been 
applied, successive fully formed white corpuscles adhering as they flowed in from 
the trunk, being evidently affected secondarily to the change induced by the 
chloroform in the tissues of the web. 

Thus the affection of the white corpuscles of the blood in an irritated part 
is in all respects strictly parallel to that of the red discs, while the greater adhesive- 
ness of which the former are capable, renders the facts regarding them more 
obvious and unmistakable. 

Being desirous to verify the results derived from the frog by observations 
upon mammalia, in which the aggregation of the red corpuscles assumes a much 
more striking appearance, I examined the wings of two small bats. In the 
first specimen, the corpuscles, both red and white, exhibited decided adhesive- 
ness within the vessels, the web being apparently in a state of irritation from 
injuries which the animal had sustained. In the other there was also some 
adhesiveness in the part that first met my eye, the red discs tending to aggregate 
into rouleaux, and giving a lumpy aspect to the somewhat dark streams in the 
larger vessels: but turning to another place, I found the blood there of pale 
tint and perfectly homogeneous aspect ; nor could I detect by a careful search 
any evidence of a tendency on the part of the white corpuscles to stick to the 
vascular parietes. It happened that there was complete absence of flow in 
one artery and concomitant vein of considerable size, yet not a rouleau was 
to be seen either in them or in any of their branches. On the contrary, the 
red discs lay at about equal distances from each other, uniformly distributed 
throughout the calibre of the vessels; and this state of things remained un- 
changed during about a quarter of an hour, in which I continued to observe 
them in their perfectly quiescent condition. On examination of some blood 
from the heart of this bat shortly after, the red corpuscles exhibited a very 
remarkable degree of adhesiveness, such as I had never seen in human blood,! 
presenting a glaring contrast with their state within the vessels.” 


* The remarkable adhesiveness of the red corpuscles of the blood of this bat, when withdrawn 
from the body, has been particularly described in Section I, p. 213. 

* Mr. Wharton Jones, in the paper before referred to, describes the red discs as aggregating within 
the vessels of the healthy bat’s wing, when their movement is arrested from any cause, in the same 
manner as in blood removed from the body. Vide Med.-Chir. Tvans., loc. cit. I suspect that the pres- 
sure of the plate of thin glass employed in order to bring the necessarily high powers of the microscope 
to bear upon the object is apt to irritate the web and give rise to a degree of congestion, characterized 
by a tendency to aggregation on the part of the red discs and adhesion of the colourless corpuscles to 
the walls of the vessels. I have observed that results of irritation have shown themselves in the web 


240 ON THE EARLY STAGES OF INFLAMMATION 


Thus we may, I think, regard it as fully established, that, in mammalia as 
well as in amphibia, both the red discs and the colourless globules of the blood 
are completely free from adhesiveness within the vessels of a perfectly healthy 
part, but that when the tissues have suffered from irritation, both kinds of 
corpuscles assume, in proportion to the severity of the affection, a degree of 
that tendency to stick to one another and to neighbouring objects which they 
possess when withdrawn from the body, and consequently experience obstruction 
to their progress through the minute vessels. 

And here I cannot avoid remarking, that this principle explains, if it does not 
altogether reconcile, the discordant opinions of physiologists regarding the 
causes of the circulation. It shows that while there is, as we have before seen,}! 
strong ground for agreeing with those who hold that the flow of the blood is 
due simply to the contractions of the heart, aided, in animals with valved veins, 
by the actions of the muscles, the respiratory movements, and, in the case of 
the bat’s wing, by rhythmical venous contractions ; yet there is also much truth 
in the view of those who maintain that the tissues of a part, independently of 
any change of calibre in the vessels, exercise a great influence upon the progress 
of the blood through the capillaries. For though the tissues do not, as has been 
hitherto supposed by the latter class of authorities, actively promote the circu- 
lation, yet their healthy condition is none the less necessary to it, being essential to 
the fitness of the blood for transmission by the heart through the minute vessels. 

It is an interesting question, whether the freedom of the corpuscles from 
adhesiveness in health is due to some active operation of the tissues upon the 
vital fluid, or whether their adhesiveness in an inflamed part or outside the body 
is the result of a prejudicial influence exerted upon the blood by the irritated 
tissues, or by the objects of the external world with which it comes in contact 
when shed. The fact that the non-adhesiveness of the corpuscles within the 
vessels continues in an amputated limb, shows that it is independent of the 
central organs of the nervous system, and probably too of any nutritive actions 
going on in the tissues. Also, if the latter were concerned in its production, 
we should expect to find the corpuscles adhesive in the large arteries and veins 
of the webs, since it is doubtless chiefly in the capillaries that the mutual inter- 
changes take place between the blood and the solid elements of the body. It 
may be difficult to obtain further evidence upon this point, but some light may 
be thrown upon it by the consideration of the causes of the coagulation of the 
blood, which seems to be a closely allied subject. 


of the frog when I have used a plate of thin glass in the same manner as with the bat, for the purpose 
of applying a high power to the pigmentary tissue. 
* See p. 220. 


ON THE BARLY STAGES OF INFLAMMATION 241 


~ 


I have shown elsewhere,’ that in mammalia, as well as in amphibia, the 
blood remains fluid for days in the veins of an amputated healthy limb, though 
retaining its property of coagulating when shed.’ Its fluidity within the vessels 
is unaffected by free admixture of the atmosphere with it. For example, seven 
hours after injecting air into the veins of an amputated sheep’s foot, I found 
the frothy mixture contained in the vessels still quite fluid ; and the blood which 
formed the bubbles, coagulated when shed. Again, a human leg having been 
amputated above the knee, I pressed out the blood from about an inch of the 
open mouth of the popliteal vein, and covered the raw surface lightly with 
a damp cloth, so as to guard against drying of the blood, or of the walls of the 
vessel in contact with it. After the lapse of twenty-four hours, the vessel was 
still patulous ; but the blood, though it had been so long freely exposed to the 
influence of the air, continued perfectly fluid. Further, if a vein in an amputated 
sheep’s foot is simply wounded, no clot forms except at the seat of wound. 
If, however, a portion of any ordinary solid matter, such as a fragment of glass, 
a bit of clean wax, a hair, a needle, or a piece of fine silver wire, be introduced 
into such a vein, a deposit of fibrine takes place after some minutes upon the 
foreign body,* followed by coagulation of the blood in that particular part of the 
vessel ; the coagulum, however, never adhering to the vein, except at the lips 
of the wound.’ This shows that an ordinary solid possesses an attraction for 


1 See a paper by the author ‘On Spontaneous Gangrene from Arteritis and the Causes of Coagu- 
lation of the Blood in Diseases of the Blood-vessels’, Edinburgh Medical Journal, April 1858 (p. 69 
of this volume). The observations there recorded, and also the others mentioned in the text with regard 
to coagulation, have been made since the reading of the original manuscript. 

* The blood coagulates more slowly the later it is examined after death or amputation, and finally 
becomes altogether incapable of the process. The time when this occurs differs in different cases. Thus, 
in the foot of the sheep I have seen coagulation take place, though slowly, on the sixth day; but in 
the human subject on one occasion I found the blood remain permanently fluid when shed within forty- 
eight hours of death, though in another instance at the same period a soft clot formed in about halt 
an hour. 

* These facts, ascertained in November 1858, have considerably modified the views expressed in 
the paper above referred to. 

* From what has been stated in the text, it is evident that the ammonia theory of Dr. B. W. 
Richardson does not account for the fluidity or coagulation of the blood within the vessels. But the 
facts mentioned by that gentleman in the valuable essay which has gained the last Astley Cooper prize, 
and also my own experience [see the paper before referred to], have convinced me that a certain amount 
of the volatile alkali does exist in freshly drawn blood, and that it has the effect of retarding the process 
of coagulation. This principle must be borne in mind in all experiments upon this subject, in order 
to understand circumstances which would otherwise be inexplicable. Thus, if the foot of a sheep be 
obtained with the blood retained in the vessels by a bandage applied before the death of the animal, 
and, after reflexion of the skin, a needle be introduced into a vein by a free opening made by the scissors, 
a deposit of fibrine will be found upon it in perhaps five minutes ; but if the needle be pushed through 
the coats of such a vein, so as to introduce it without previous wound of the vessel, and allow little 
opportunity for escape of ammonia, the deposit will not take place for a quarter of an hour or more. 
Again, the blood obtained by wounding a vein immediately after reflecting the skin, within the first 
few hours after the death of the animal, takes a much longer time to coagulate than the blood shed from 
the same vessel after the lapse of half an hour or so; doubtless in consequence of escape of ammonia 

LISTER I R 


242 ON THE EARLY STAGES OF INFLAMMATION 


the particles of the fibrine, such as is not exercised by the walls of the vessels ; 
or, in other words, that the vascular parietes differ from all ordinary solid sub- 
stances in being destitute of attraction for that element of the liquor sanguinis. 

The blood-vessels are not the only constituents of the animal body which 
have these remarkable relations to the blood. If the integument of a sheep’s 
foot be partially reflected, and one of the subcutaneous veins immediately 
wounded, so as to let some blood run into the angle between the skin and the 
rest of the limb, before any drying of the tissues has occurred, care being taken 
that no hairs or other solid matters have been introduced, this blood will remain 
in whole or in part fluid for half an hour or more ; whereas, if blood from the same 
vessel be placed in contact with any ordinary solid, whether on the foot or else- 
where, it will coagulate in perhaps five minutes.' This is sufficient proof that 
the subcutaneous cellular tissue resembles the lining membrane of the vessels 
in its conduct towards the blood. The long time during which blood has been 
observed to remain fluid but coagulable in the tunica vaginalis, seems to show 
that serous membranes are similarly circumstanced: and it appears probable 
that the same may be the case with other tissues. fp 

But though some of the facts above mentioned furnish clear evidence that 
ordinary solid matter induces coagulation by an attractive agency, it by no 
means follows that the tissues are necessarily merely neutral in their conduct 
towards the blood in this matter. It is quite possible that they may exert 
an active influence upon it, in consequence of which the particles of fibrine 
may experience a mutual repulsion, in the same way as would seem to be the 
case with the pigment-granules of the chromatophorous cells of the frog during 
the process of diffusion,? Indeed some such hypothesis seems almost necessary 


having occurred in the interval. This circumstance seems to prove that the ammonia is free in the 
blood in its normal condition within the vessels, and not merely liberated during the process of coagu- 
lation ; for it is to be remembered that the mere wounding of a vein in no way interferes with the fluidity 
of the blood in it, except at the wound. 

* After the blood has lain for some time in the angle between the skin and the limb, it coagulates, 
if removed from it, much more rapidly than blood freshly shed,from a vessel. Thus, in one case, blood let 
out from a vein was part of it placed at once on a glass plate, and part allowed to run into the angle 
between the skin and limb. That on the glass plate was not completely coagulated for ten minutes ; 
but that in the other situation, having been left for twenty minutes, and then transferred to the plate, 
was a consistent clot within six seconds, indeed as soon as I could examine it. This fact seems to me 
to throw great light upon the subject of coagulation. The sudden transition from perfect fluidity to 
a coagulum can only be explained, I conceive, on the hypothesis that the ammonia had almost all escaped 
while the blood lay in the angle ; yet this escape had not caused coagulation. Hence it seems to follow, 
that ammonia is in no way essential to the fluidity of the blood while it is surrounded by healthy tissues. 
Another point, which the simple experiments upon the sheep’s foot show clearly, is that a certain amount 
of ammonia in the blood will retard without preventing the deposit of fibrine upon a needle or other 
ordinary solid introduced into the vessels; and it appears very doubtful whether healthy blood ever 
contains sufficient ammonia to prevent such an occurrence. 

* See p. 56 of this volume. 


ON, RHE EAREY STAGES OF INFLAMMATION 243 


in order to explain the remarkable fact, that the blood coagulates within a few 
hours of death in the cavities of the heart and great venous trunks, though it 
retains its fluidity for days in the smaller vessels. Thus in the human subject 
twenty-four hours after death I have found clots in the heart and larger veins, 
including the upper parts of the axillary and femoral trunks, but fluid blood 
in the lower parts of those vessels and all their branches in the limbs. It seemed 
possible at first that this difference might depend on the position of the great 
vessels in the thorax and abdomen, where decomposition begins earlier than in 
the limbs. But this proved not to be the case; for in a horse twelve hours 
after it had been killed, I found the blood fluid in the intercostal and small 
cardiac veins, though coagulated in the vena cava and the coronary vein of 
the heart, which is in that animal of very large size. There being no reason 
to suppose the walls of the larger vessels differently constituted from those of 
the smaller ones, or more lable to undergo post mortem changes, the natural 
interpretation of these facts seems to be that the blood has, even within the 
body, a certain tendency to coagulation, counteracted by an influence exerted 
upon it by the containing tissues, which, operating to less advantage the larger 
the mass of the fluid acted on, fail, at least after death, to prevent it from follow- 
ing its natural course in vessels of a certain magnitude. Again, if we suppose 
that the tissues are merely passive with regard to the blood, it seems difficult 
to understand the rapid solidification of a large quantity shed into a cup. For 
we have seen that mere exposure to the atmosphere will not account for the 
fact ; while at the same time the experiments upon the sheep’s foot indicate 
that an ordinary solid has but a very limited range of operation upon the sur- 
rounding blood,’ and that the clot which it induces does not propagate itself 
to more distant parts; so that the central portions of such a mass of blood 
should remain fluid, unless we admit that, when shed from the vessels, it is 
liberated from an influence which previously kept in check a spontaneous 
proneness to coagulation. Hence it seems likely that a foreign solid intro- 
duced into a vein acts not by creating a disposition to aggregate on the part 
of the fibrine, but by increasing a pre-existing tendency to it (as a thread 
induces the crystallization of sugar-candy), exalting the mutual attraction 

* I find that if a needle is introduced into a vessel and removed after the expiration of about two 
minutes, before any deposit of fibrine has yet occurred upon it, a certain amount of coagulation never- 
theless takes place afterwards in that particular part of the vessel in which the needle had lain. This 
is a curlous circumstance, indicating that an impression leading to coagulation is produced upon the 
blood by contact with an ordinary solid for a shorter time than causes, during its presence, any visible 
solidification. The clot, however, is very slow in forming and very incomplete, so that such cases cannot 
be compared with the perfect and rapid coagulation of a large mass of blood outside the body. Indeed, 
when blood is drawn into a large cup, a great deal of it never touches the side (the ordinary solid) even 


for an instant. 
Rr2Z 


244 ON THE EARLY STAGES OF INFLAMMATION 


of its particles to a degree which overcomes a counteracting agency on the 
part of the tissues. 

Further inquiry will, in all probability, throw clearer light upon this subject, 
but in the meantime the facts already known furnish to the unaided senses 
indisputable proof of the fundamental principle to which we were led by micro- 
scopical observation, viz. that the tissues through which the blood flows have, 
when healthy, special relations to the vital fluid, by virtue of which it is main- 
tained in a fit state for transmission through the vessels. Further, the differ- 
ences of adhesiveness in the corpuscles according as the blood is surrounded 
by healthy tissues or ordinary matter, can now be no longer matter of surprise, 
knowing as we do the alterations which take place in the chemical condition 
of the liquor sanguinis in consequence of such changes of circumstances, and 
also the great effect produced upon the adhesiveness of the red discs in blood 
outside the body by slight variations in the quality of the plasma.’ 

The freedom from attraction for the fibrine, if not the actual repulsion of 
it, on the part of the walls of healthy blood-vessels, seems to explain the well- 
known fact in pathology, that when healthy capillaries are subjected to abnormal 
pressure in consequence of venous obstruction, the fluid squeezed through their 
parietes consists almost exclusively of serum; the fibrine being apparently 
excluded from their pores as liquid mercury is from those of flannel, or any other 
texture composed of a material destitute of attraction for it. 

From the speedy coagulation of lymph effused into the interstices of in- 
flamed organs or upon inflamed serous surfaces, compared with the length of 
time that blood has been known to remain fluid after being poured out into 
such situations in a state of health, and also from the deposition of fibrine 
which occurs at an early period upon the lining membrane of the vessels in 
arteritis or phlebitis, whether in the limited inflammation which results from 
the application of a ligature, or in the more extensive affection which is apt 
to occur spontaneously, it would appear that the liquor sanguinis, like the 
corpuscles, tends to comport itself near inflamed tissues as if in the vicinity of 
ordinary solid substances. It is true that coagulation is not observed to occur 
in the vessels of the frog’s web after the application of irritants; but this is 
accounted for by the length of time required for the occurrence of the process 
within the vessels, the liquor sanguinis passing on into healthy regions, leaving 
the adhesive corpuscles behind it. Adhesiveness of corpuscles may, however, 
come on in circumstances which admit of permanent fluidity of the blood. 
Thus if a cat be killed without haemorrhage, and one of the jugular veins be 
exposed and tied in two places, and the animal be then suspended by the head 


+ see Section I, p. 214. 


ON THE EARLY STAGES OF INFLAMMATION 245 


so that the vein may be vertical in position, the upper part of the venous com- 
partment included between the ligatures will within a very few minutes become 
colourless in consequence of rapid subsidence of the red corpuscles, implying 
that they are already closely aggregated, although, if the skin be carefully 
replaced so as to prevent drying of the tissues, the blood will remain fluid in 
that part of the vein for many hours. Whether the adhesiveness of the cor- 
puscles in this case depend on a post mortem change in the vessels, or whether 
it is merely the result of the large size of the vein preventing the tissues from 
acting effectually on the blood, remains to be determined; but such a fact 
seems to prove that a higher grade of vital activity, so to speak, is required 
to prevent adhesiveness of corpuscles than to maintain the fluidity of the blood. 
Hence it is probable that, even if the blood were at rest in the vessels of a part, 
a stronger degree of irritation would be required in order to determine coagula- 
tion than would suffice to induce adhesiveness of the corpuscles, which seems 
to be a more sensitive test of a deviation of the tissues from the standard of 
health. I have, however, ascertained, by experiments upon the amputated 
sheep’s foot, that if caustic ammonia is applied freely to a part of a vein after 
pressing the blood out of it, and the blood allowed to return when the ammoniacal 
odour has passed off, coagulation takes place in the portion of the vessel which 
has been so treated, although the chemical action of ammonia, if any of it 
remained in the tissues, would tend to prevent or check coagulation.t. I have 
also found a similar local clot form, though more slowly, after merely pinching 
a piece of a vein. 

The principal results obtained in this section may be summed up as 
follows :— 

The effects produced upon the circulation by the application of an irritant 
to a vascular part are twofold, consequent upon two primary changes in the 
tissues, which, though often concomitant, are entirely independent both in 
nature and mode of production. One of these is dilatation of the arteries 
(commonly preceded by a brief period of contraction), giving rise, in proportion 
to the increase of calibre, to more free flow through the capillaries, the blood 
remaining unaffected, except in the rate of its progress. This purely functional 
phenomenon is developed indirectly through the medium of the nervous system, 
being not limited to the part acted on by the irritant, but implicating a sur- 
rounding area of greater or less extent. The other change is the result of the 
direct operation of the irritating agent upon the tissues, which experience some 
alteration, in consequence of which the blood in their vicinity becomes impaired, 
losing the properties which characterize it while within a healthy part, and 


* See the paper ‘On Spontaneous Gangrene’, &c., before referred to. 


246 ON THE EARLY STAGES OF INFLAMMATION 


which render it fit for transmission through the vessels, and assuming those 
which it exhibits when removed from the body and placed in contact with 
ordinary solid matter. The first indication of this disorder of the vital fluid is, 
that its corpuscles, both red and white, acquire some degree of adhesiveness, 
which makes them prone to stick to one another and to the vascular parietes, 
and, lagging behind the liquor sanguinis, to accumulate in abnormal numbers 
in the minute vessels. This adhesiveness may exist, in proportion to the severity 
of the affection, in any degree, from that which merely gives rise to a very slight 
preponderance of the corpuscular elements of the blood in the part, up to that 
which induces complete obstruction of the capillaries ; and when the irritation 
has been very severe, the liquor sanguinis also shows signs of participation in 
the lesion by a tendency to solidification of the fibrine. 


SECTION WY 
On the Effects of Irritants upon the Tissues. 


The object of the present section is to inquire into the nature of that primary 
change which we have seen to be produced in the tissues by the direct action 
of irritants upon them. 

The conclusion already arrived at, that blood flowing through an irritated 
part approaches more and more nearly, in proportion to the intensity of the 
affection, the condition which it assumes when separated from the living body, 
naturally leads us to infer that the tissues concerned are in some degree approxi- 
mated to the state of ordinary matter, or, in other words, have suffered a diminu- 
tion of power to discharge the offices peculiar to them as components of the 
healthy animal frame. 

This inference is strongly supported by considering what common effect is 
likely to be produced upon the tissues of the frog’s web by all the various agents 
known to cause inflammatory congestion. To take first the case of mechanical 
violence. A forcible pinch of the delicate web seems likely, a priori, to impair 
its powers ; for if the lesion be sufficiently severe, complete death of the part 
will result. An elevated temperature proves equally destructive if carried far 
enough ; and its operation to a degree just short of this, while it produces con- 
gestion, can hardly fail to cause diminished vigour in the tissues. So also 
powerful chemical agents, if used cautiously, give rise to inflammation; but 
if otherwise, kill the part they act on. Even the pungent irritants which do 
not exert much chemical action, seem to benumb the energies of the spot to 
which they are applied. Thus a morsel of capsicum placed on the tip of the 


ON THE SPARE Y SIAGES OF INFLAMMATION 247 


tongue speedily produces numbness there, and a piece of mustard lying on 
the finger for an hour or two dulls the sensibility of the skin. Chloroform, too, 
while it very readily induces stagnation followed by vesication in the frog’s 
web, is an agent which appears likely to benumb the vital energies. If a small 
frog be put into a bottle of water highly charged with carbonic acid, and removed 
from it some time after all motion of the limbs has ceased, it will be found that, 
though the heart is still beating, the blood-vessels of the webs are loaded with 
stagnant corpuscles. After a while, however, resolution will take place, and 
some time later the animal will regain its consciousness. Here it appears pro- 
bable that the carbonic acid, poisoning the web as well as the brain, paralyses 
for a time the functional activity of both ; and that the return of the circulation, 
like the recovery of the cerebral functions, depends on a restoration of the 
dormant faculties of the affected tissues. 

Perhaps the most instructive case is that of the galvanic shock, which the 
following circumstances first showed me to be capable of causing inflammatory 
congestion. Being desirous of ascertaining the effects of galvanism upon the 
cutaneous pigmentary system, I applied the poles of a battery in rather powerful 
action to the skin of the head of a frog, when, the shock affecting the brain, 
the animal was stunned and lay perfectly motionless. This state of things 
being favourable for pursuing my inquiry by aid of the microscope, I drew 
down one of the passive limbs, and having placed the foot under the instrument, 
arranged the fine platinum-wire extremities of the poles at a short distance 
from one another at opposite sides of one of the webs, so that the current might 
pass through a part in the field of view, the circulation meanwhile remaining 
healthy. I now completed the circuit of the battery, when the leg became 
instantly drawn up by reflex action ; yet on re-examination of the web, I found 
that, momentary as the shock had been, the part through which it had passed 
had become affected with intense inflammatory congestion, gradually shading 
off towards the healthy condition, which existed at a little distance. After 
about a quarter of an hour resolution of the confused mass of stagnant corpuscles 
occurred, and shortly after this the creature regained the power of voluntary 
motion. I afterwards repeated the experiment, both upon the same animal 
and upon another specimen, and always with the same results ; and I particu- 
larly observed in one case that the white corpuscles were affected with great 
adhesiveness in the congested region. 

With regard to the manner in which the abnormal condition of the blood 
was brought about in these cases, it has been already mentioned in Section I 
that the galvanic current produces no increase of the adhesiveness of the red 
corpuscles of blood outside the body ; but after what has been stated in the 


248 ON THE EARLY STAGES OF INFLAMMATION 


last section, the reader will see no reason to think such an effect likely. It 
may, however, seem not improbable that the galvanic shock might, by its direct 
action upon the blood within the vessels, reduce it to the same condition as if 
removed from the body. But that this was not really the cause of the con- 
gestion, was clear from the fact that in the parts less intensely affected, where 
the corpuscles still moved slowly though possessed of considerable adhesiveness, 
the same condition continued long after all the blood which was in the vessels 
when the shock was transmitted had passed away. In this case, therefore, as 
in all the others which we have considered, the blood was affected secondarily 
to the tissues. This being established, the natural interpretation of these 
experiments appears to be, that the portion of the web affected was, as it were, 
stunned by the shock, and its functions suspended like those of the brain; the 
resolution of the inflammation, like the return of volition, depending on recovery 
of function on the part of the tissues concerned. 

From such considerations as these, it appears that all those agents which 
produce inflammatory congestion when applied to the web, though differing 
widely in their nature, agree in having a tendency to inflict lesion upon the 
tissues and impair their functional activity. 

But powerful as are the arguments thus obtained by inference, it is very 
desirable to confirm them by direct observation, and it fortunately happens 
that the cutaneous pigmentary system of the frog is a tissue which discharges 
functions very apparent to the eye, so that it is easy to trace their modifications 
under the influence of irritation. 

In the first experiment with mustard described in the last section (per- 
formed September 29, 1856), the space on which the irritant had acted presented 
a very striking difference from the rest of the web in the appearance of the pig- 
ment, which in healthy parts was in the form of small roundish black dots ; 
while in the mustard area, and accurately corresponding to the extent of stag- 
nation in the capillaries, each spot was extended to a stellate figure. 

I thus became for the first time aware that the pigment is capable of varia- 
tions, and my attention having been directed to the subject, I soon found that 
similar changes occur spontaneously, and give rise to alterations in the colour 
of the skin, which is paler in proportion as the colouring matter is more com- 
pletely collected into round spots. For some weeks I supposed myself to have 
been the first discoverer of this curious fact, till I was referred by Dr. Sharpey 
to the recent labours of the Germans on the subject. They, however, as I after- 
wards found, had taken an entirely erroneous view of the phenomenon, attributing 
the round form of the masses of pigment to contraction of the branching offsets 
of stellate cells ; whereas it turned out that the chromatophorous cells do not 


ON THE EARLY STAGES OF INFLAMMATION 249 


alter in form, but that the colourless fluid and dark molecules which constitute 
their contents are capable of remarkable variations in relative distribution, the 
molecules being sometimes all congregated in the central parts of the cells, the 
offsets containing merely invisible fluid, while at other times the colouring 
particles are diffused throughout their complicated and delicate branches ; and 
between these extremes any intermediate condition may be assumed. It 
further appeared that concentration of pigment takes place in obedience to 
nervous influence, while diffusion, though also an active vital process, tends 
to occur when the pigment-cells are liberated from the action of the nerves. 
But for further particulars on this subject, I beg to refer the reader to a 
previous paper in this volume." 

The contrast between the pigment in the area on which the mustard had 
acted and that of surrounding parts in the case last alluded to, at once struck 
me as probably the result of a direct action exercised upon the tissues by the 
irritant. It seemed possible, however, that it might be a secondary effect of 
the state of the blood in the congested vessels ; and in order to ascertain which 
was the truth, I performed, on the 14th of October the following experiment :— 

Having cut out a piece of the web of a healthy frog, I placed a small portion 
of mustard upon its centre when all the blood had escaped fromit. After a while 
the spots of pigment seen through the thin margin of the mustard, presented 
a stellate form, while in the rest of the piece they were still of a rounded figure. 
Hence it was clear that the change in the disposition of the pigment was the 
result of the direct action of the mustard upon the tissues of the web. 

A new field of investigation was thus opened before me, promising to throw 
great light upon the nature of inflammation. 

To explain the effects of irritants upon the pigmentary tissue proved, 
however, to be a matter of considerable difficulty. Tincture of cantharides and 
croton oil, which happened to be among the first substances which I employed 
with reference to this subject, resembled mustard in causing diffusion of the 
pigment. Taking, in the first instance, the same view of this change as the 
German authorities, I attributed it to the relaxation of contractile cells, and 
regarded its occurrence, in consequence of irritation, as an indication of loss 
of power in the tissues, a view which was in harmony with the nature of the 
derangement of the blood in a congested part. Croton oil, curiously enough, 
acted very slowly on the web, not producing any change on either pigment or 
blood for an hour or more : also its effects appeared inconsistent with my theory ; 
for while it ultimately gave rise to diffusion of the pigment to even a greater 
extent than I had seen occur with mustard, yet it induced only comparatively 


HSEE Pps 4d St Seq. 


250 ON THE EARLY STAGES OF INFLAMMATION 


slight appearances of congestion. Chloroform also seemed at first still more 
anomalous in its operation, though in the opposite way; for though it was 
pre-eminently potent in inducing congestion, it caused no alteration whatever 
in the appearance of the pigment, whether mildly or strongly applied. 
Afterwards, as the true nature of the pigmentary functions became un- 
veiled, and further facts were developed, these difficulties were completely 
cleared away. The first step towards their solution was made in an experiment 
with ammonia. A frog being placed under chloroform, I covered the whole 
of the foot with sweet oil, except a small area in one of the webs, the pigment 
being in the stellate condition, i.e. about midway between perfect concentration 
and full diffusion. An assistant then held at a short distance above it a piece 
of lint soaked in the strongest liquor ammoniae, so that its pungent alkaline 
vapour might play upon the exposed area, while the rest of the foot was protected 
by the oil. This having been continued for a few seconds, accumulation of 
corpuscles and stagnation occurred in the vessels of the area, without any change 
in the appearance of the pigment. After a while, however, the creature happened 
to grow pale, and, in the web generally, the pigment became completely con- 
centrated so as to assume the dotted aspect, but in the part which was the seat 
of congestion it remained stellate as before. Hence it appeared that though 
the ammonia did not cause any change in the distribution of the pigment, it 
had in reality produced a great effect upon the chromatophorous cells, which, 
in the area exposed to its influence, had been deprived of the power of concen- 
tration by the mildest degree of action of the alkali that sufficed to induce 
stagnation of the blood. On examination of the web about four hours later, 
resolution of the stagnation was found to have taken place, though there was 
still some excess of corpuscles, with marked adhesiveness of the colourless ones 
in the vessels of the ammonia area. The creature was now released for the 
night. Next morning the integument was in the opposite extreme of colour, 
being almost black, and the pigment had the reticular appearance, being fully 
diffused throughout the whole web, except the central part of the ammonia area, 
where it retained the same stellate condition as the day before. Hence it ap- 
peared probable that the diffusive power, as well as the concentrating, had been 
paralysed by the ammonia, but had been recovered in all the area except the 
part that was likely to be the last to regain its functions. To ascertain whether 
the concentrating power had also been regained, I killed the frog and amputated 
the leg; soon after which the usual post mortem concentration took place 
completely in the web generally, while in the central part of the area the medium 
state was still retained, and in the rest of its extent concentration considerably 
beyond the medium state, but short of the full degree, supervened, showing 


ON THE EARLY STAGES OF INFLAMMATION 251 


that recovery of function had taken place to a considerable extent, but was not 
yet quite complete. 

I now felt little doubt that chloroform also possessed the power of arresting 
the pigmentary functions ; but in order to prove the fact I killed a dark frog, 
and placed one of its legs in that fluid for half a minute, and then wrapped 
both it and the other leg in damp lint. After some hours the limb which had 
not been treated with chloroform was quite pale, while the other, having lost 
the faculty of post mortem concentration, remained as dark as before. The 
appearance presented by the pigment in the two feet is shown in Plate III 
(page 68), Figs. 1 and 2. 

Mechanical violence proved similar in its effects on the pigment, which, 
in the area pinched, retained the same appearance as before, except that in 
parts where the pressure operated most severely the cells seemed sometimes 
to have suffered rupture. Fig. 2, Plate V is a camera-lucida sketch of part 
of a spot which had been compressed by means of padded forceps, with an 
adjoining uninjured portion of the web. The pigment was fully diffused before 
the experiment was performed, and remained so afterwards in the area squeezed, 
while it became concentrated elsewhere, and this was the condition of things 
when the drawing was made. The concomitant differences in tint between the 
blood in the affected and the sound parts in consequence of the accumulation 
of closely packed red discs in the former, are also strikingly shown in the sketch.! 

The galvanic shock, too, produced no effect apparent to the eye upon the 
pigment of the parts in which it caused stagnation of the blood, but experiments 
afterwards made showed me that, like ammonia, it exerted a paralysing agency 
both upon the concentrating and the diffusive powers ; and the same results 
ensued on the application of dry heat in the cases mentioned in the last section. 

From these and other similar facts it appeared that mustard, croton oil, 
and cantharides are exceptional as regards the diffusion to which they give rise, 
the usual course being that irritants, when applied so as to produce stagnation 
of the blood, suspend at the same time both the functions of the pigment-cells. 

It afterwards turned out that mustard was, in reality, no exception to 
this general rule. Subsequent experiments showed that diffusion takes place 


* Much more gentle pressure, if long continued, may give rise to similar results, as I happened to 
notice in the following manner. Being desirous of watching the process of post mortem concentration 
of the pigment, I amputated a leg of a dark frog, and, having stretched out the foot over a glass plate, 
put a small piece of thin glass upon part of one of the webs, and applied a high power of the microscope 
to it. I was disappointed to find, however, that the change I wished to observe did not take place ; 
but on looking at other parts of the web, found that immediately beyond the edge of the slip of thin 
glass the pigment was on all sides considerably concentrated, although remaining fully diffused where 
the glass covered it; an effect which I could attribute only to the gentle squeezing to which the two 
plates subjected the part of the web that lay between them. 


252 ON THE EARLY STAGES OF INFLAMMATION 


to very different degrees in different instances under the action of this substance, 
but that in all cases, after reaching a certain point, it becomes incapable of ad- 
vancing further in the irritated part, however much it may increase in the body 
generally, in case of the animal changing to a darker colour. These differences 
depend partly upon the strength of the mustard, the diffusion being least when the 
irritant is most potent. Thus, on one occasion, when a solution of the volatile 
oil in spirit of wine was applied to a web in which the pigment was fully con- 
centrated, congestion was very rapidly developed, without any alteration in 
the appearance of the chromatophorous cells. That the diffusion is in inverse 
proportion to the energy with which the mustard acts, was well illustrated by 
the experiment which furnished the drawing given in Plate V, Fig. 1.'_ In that 
case, a frog having been prepared in the manner mentioned in the note to p. 32, 
a portion of very strong mustard was placed upon the middle of one of the webs, 
the pigment being in the stellate condition, such as is seen on the left-hand side 
of the sketch, which represents a part of the edge of the spot to which the irritant 
was applied, together with an adjoining portion of the web. Shortly after 
this had been done, I noticed that the pigment was in a state of full diffusion in 
a ring round about the opaque mass, producing the reticular appearance shown 
in the stripe down the middle of the sketch. I had in a previous case seen 
a similar ring become affected with congestion, when a portion of mustard 
had been applied for a long time, in consequence of the pungent vapour of the 
volatile oil playing upon the neighbouring parts of the web, and there could 
be no doubt that the effect on the pigment in the present instance was due to 
the same cause ; but in the latter no material change was as yet visible in the 
blood except close to the edge of the mustard, where the corpuscles were seen 
to be abnormally adhesive. After the lapse of about an hour, the area on which 
the irritant had lain being examined, was found to be the seat of the most intense 
inflammatory congestion, indicated in the drawing by the crimson colour of the 
vessels, but the pigment there had experienced only an exceedingly slight degree 
of diffusion, being, in fact, almost exactly in the same state as at the commence- 
ment of the experiment. Thus the vapour of the volatile oil, though operating 
too mildly to cause inflammatory congestion, nevertheless induced the highest 
possible degree of pigmentary diffusion ; but the mustard, where it lay actually 
in contact with the web, and acted energetically upon it, arrested that very 
process of diffusion to which its gentler operation gives rise. 

In the progress of the case it happened that the animal changed from the 
medium tint which it had at first to a very pale colour, the pigment, in the web 
generally, assuming the dotted condition depicted on the right-hand side of 


' This experiment was performed subsequently to the reading of the paper. 


ON THE EARLY STAGES OF INFLAMMATION 253 


the drawing. Yet many hours after the mustard had been removed, the pig- 
ment on which it had acted retained its stellate disposition, and the reticular 
appearance in the surrounding ring also remained unchanged, showing that the 
power of concentration had been permanently lost in those parts, and affording 
a favourable opportunity for obtaining by means of the camera lucida a delinea- 
tion of the medium, and both extreme conditions of the pigment in the same 
web. Next day the experiment was rendered still more instructive by the 
skin becoming excessively dark, the pigment undergoing full diffusion in the 
healthy parts of the web, so that the contrast between the ring about the con- 
gested area and the surrounding regions no longer existed: yet the stellate 
condition was still maintained where the mustard had lain, showing that it had 
suspended the faculty of diffusion no less than that of concentration. 

Croton oil now no longer seemed anomalous in its operation. Its curiously 
slow action upon the frog is comparable to the mild influence of the vapour 
of mustard, and the slight amount of inflammatory appearance which I had 
sometimes observed in a part where it had caused a great degree of pigmentary 
diffusion, is strictly analogous to the healthy state of the circulation in the 
reticular ring round the congested area in the last experiment. 

Cantharides also presents a parallel case. Its action is even more slow 
than that of croton oil; and on referring to notes taken at an early period 
in this investigation, I find that in one instance, when two hours and a half 
had elapsed after the application of a small drop of the tincture to the web, 
though diffusion of the pigment had become apparent in the area on which it 
had acted, no change of the blood had yet been observed ; and an hour and 
a half later, the red corpuscles, though abnormally adhesive as compared with 
those in surrounding parts of the web, were still moving slowly through the 
vessels. 

Hence it appears that diffusion of the pigment may be produced by either 
of these three substances without the blood undergoing any material derange- 
ment, and therefore that its occurrence under their influence is to a great extent, 
if not entirely, independent of the inflammatory process. On the other hand, 
it has been. demonstrated, as regards mustard, that when stagnation of the 
blood has been developed through its action, the state of the pigment-cells is 
the same as is induced by irritants generally, viz. a complete suspension of 
functional activity ; and, from analogy, we may be pretty sure that this is 
also true of croton oil and cantharides, although their slow operation renders 
it difficult to obtain absolute proof upon the point. 

In a physiological point of view, it is an interesting question, what is the 
cause of the diffusion of the pigment induced by these three irritants. I have 


254 ON THE EARLY STAGES OF INFLAMMATION 


shown elsewhere! that concentration is the invariable result of the action of 
the nerves upon the chromatophorous cells, and that diffusion takes place 
whenever they are liberated from nervous influence. Also in the tree-frog of the 
Continent, which is much more liable to changes in the colour of the integu- 
ment, in consequence of direct irritation, than our own species, the invariable 
experience of the German observers was, that concentration followed the applica- 
tion of a local stimulus, while secondary diffusion sometimes occurred in the 
irritated spot, depending apparently upon exhaustion.2. From these facts, 
diffusion ensuing on irritation cannot well be regarded as an increased action 
excited by the stimulus, but rather as an evidence of diminished vigour, With 
croton oil and cantharides, which have not an irritating vapour, the diffusion 
is exactly limited to the extent of the irritant, showing that it is due to a direct 
action on the tissues; and the most probable explanation of its occurrence 
appears to be that mustard, croton oil, and cantharides have the peculiarity 
among irritants of affecting the nerves of the pigment-cells in the part they act 
on, somewhat more rapidly than the cells themselves, and, paralysing the former 
while the latter still retain their powers more or less intact, permit diffusion 
to go on unrestrained by nervous influence, till the further operation of the 
irritant completely suspends the pigmentary functions. It may be objected 
to this view, that diffusion occurs on the application of these substances to an 
amputated limb, but, from evidence given elsewhere,’ it is probable that the 
pigment-cells possess a local nervous apparatus, on which the occurrence and 
maintenance of post mortem concentration depend, and the paralysis of which, 
while the pigment-cells retain their powers, would give rise to diffusion in an 
amputated limb. Be this as it may, the fact that the state of full diffusion 
continued in the ring around the congested area in the last mustard experiment 
for hours after the irritant had been removed, although, during that time, com- 
plete concentration occurred in the web generally, is pretty clear evidence that 
the pigment-cells in that part had not merely been stimulated to increased 
action (for in that case they would have returned to their former condition 
soon after the stimulus had ceased to operate), but had suffered a loss of the 
faculty of concentration. Whether the loss of power resided in the nerves 
of the pigment-cells, or in those cells themselves, is a matter of indifference as 
regards the objects of the present inquiry ; the important fact being that an 
action of the mustard so mild as to give rise to little or no derangement of the 
blood, nevertheless produced a certain degree of loss of power in the part on 
which it operated. There can be no doubt that the same principles apply to 
the cases of croton oil and cantharides ; and thus the diffusion caused by these 


+ See the paper ‘On the Pigmentary System ’, p. 64. *SSEP pis; * See p. 63. 


ON THE EARLY STAGES OF INFLAMMATION 255 


three irritants assumes a high interest, as visible evidence of diminished functional 
activity accompanying, if not preceding, the earliest approaches to inflammatory 
congestion in parts which have been subjected to their influence. 

With the view of ascertaining the nature of the effect produced on the 
pigment-cells by the mildest action of chloroform which is capable of causing 
inflammatory disorder, I ascertained, by repeated experiments, the shortest 
time in which the vapour of that liquid gave rise to unequivocal signs of a con- 
gestive tendency in the web of the living frog; and having found this to be 
about half a minute, suspended for that period one of the legs of a recently 
killed dark frog in a vessel, the bottom of which was covered with chloroform, 
having previously examined the webs microscopically, and found that full diffu- 
sion of pigment existed throughout them. The result was that the limb exposed 
to the chloroform vapour remained dark, while the other became gradually pale. 
On re-examination of the former after some hours, each web presented stripes 
of full diffusion of pigment alternating with others in a medium condition ; their 
direction being at right angles to the margin of the web. The longitudinal 
folds in which the webs had happened to be, had prevented the chloroform 
vapour from gaining equally free access to all parts ; yet the chromatophorous 
cells in the stripes that had been thus partially protected from its influence had 
been incapable of complete concentration, showing that even the exceedingly 
slight degree of action which the chloroform could have exerted upon these 
places sufficed to diminish, though not to destroy, the functional activity of 
the pigmentary tissue. 

In one of the experiments performed in order to determine the effect of 
mechanical violence, as before alluded to, the pigment remained unchanged 
for days in the area which had been pinched, while varying in other parts of 
the web ; yet, though great excess of red corpuscles existed in the vessels of the 
affected spot, they never ceased to move; showing that the functions of the 
pigment-cells might be completely suspended by a degree of irritation short of 
that which occasions actual stagnation of the blood. 

The same thing was afterwards? seen in a case in which a small drop of 
wood-vinegar was placed upon one of the webs of a frog which had been deprived 
of the power of voluntarily moving the limbs by passing a knife between the 
occiput and the atlas, so as to sever the brain from the cord. The fluid being 
thus allowed to lie quite undisturbed, did not spread at all upon the web, which 
was dry before it was applied. It produced its effects very slowly, so that, 
after the lapse of three and a half hours, the blood in the area covered by it, 
while everywhere presenting inflammatory appearances, was still only partially 


* This experiment was performed subsequently to the reading of the paper. 


2506 ON THE EARLY STAGES OF INFLAMMATION 


stagnant. Yet throughout this space the pigment retained exactly the same 
moderate degree of diffusion as it had at the beginning of the experiment, 
although in the interval complete concentration had taken place elsewhere ; 
and a very striking contrast was presented between the stellate pigment with 
the adhesive though still moving blood-corpuscles, where the web was wet with 
the vinegar, and the dotted pigment and perfectly healthy circulation in the dry 
parts immediately adjacent. 

Seeing, then, that complete suspension of the pigmentary functions may be 
caused by an amount of irritation which induces only a minor degree of congestion, 
and further, that (as we learn from the experiment with chloroform vapour) 
a still milder operation of an irritant renders these functions sluggish though 
not completely arresting them, we seem to have sufficient evidence that impair- 
ment of the functional activity of the chromatophorous cells occurs in the very 
earliest stages of that primary change in the tissues which leads to inflammatory 
derangement of the blood. 

It was seen in the ammonia experiment related above, that resolution 
having taken place in the congested area, the pigment-cells of the part recovered 
the faculty both of diffusion and concentration. This might have been pretty 
confidently predicted; for as congestion is a necessary consequence of the 
disorder produced in the tissues by irritants, we might have been almost sure 
that the return of the vital fluid to that healthy condition in which it 1s fit for 
free transmission through the vessels, must be preceded by a restoration of 
the living solids to their normal state. In the case alluded to, however, no sign 
of recovery of the pigment-cells appeared till after the circulation had become 
re-established ; and even when several hours had elapsed, they still remained 
paralysed in the central part of the area on which the ammonia had acted. 
This is in harmony with the fact lately pointed out, that complete suspension 
of the pigmentary functions may accompany a state of the blood short of actual 
stagnation ; and both appear to depend upon the circumstance that the chro- 
matophorous cells are an extremely delicate form of tissue. 

The rate of recovery of the pigment-cells varies greatly, however, in different 
cases, and in this respect much depends upon the nature of the irritant. An 
example of an agent of this class producing only very transient effects on the 
pigmentary functions is presented by carbonic acid. It has been before men- 
tioned that the immersion of a living frog for about a quarter of an hour in 
water highly charged with that gas, gives rise to complete stagnation of the 
blood in the webs, although the heart still continues beating, but that resolution 
occurs after the animal has been exposed for a while to the atmosphere. With 
a view to ascertaining whether the congestion was due to the direct action of 


ON THE EARLY STAGES OF INFLAMMATION 257 


the acid upon the tissues, I made the following experiment. Having killed 
a dark frog and amputated both legs, and ascertained by microscopic examina- 
tion that the pigment was fully diffused in the webs, I put one limb into a bottle 
of ‘ aerated water’ and the other into ordinary water: the latter soon became 
pale through post mortem concentration, but the former remained as dark as 
ever during the two hours for which it was retained in the solution of carbonic 
acid, the direct action of which upon the bloodless tissues was thus demonstrated. 
An hour after the limb had been taken out, however, it was evidently recovering, 
being distinctly lighter in colour than it had been, and two hours later it was 
quite pale, and the pigment in the webs was found to be in almost the extreme 
degree of concentration. In subsequent similar experiments I left the leg in 
the aerated water for a longer time, during which it always retained precisely 
the same tint that it had when first introduced ; and, if left for many hours, 
showed signs of loss of vitality, by the early supervention of cadaveric rigidity 
and exfoliation of the epidermis; but if it was taken out within about four 
hours, the pigment-cells recovered completely; and in one case a leg not 
removed for nine hours regained, nevertheless, to a considerable extent, the 
faculty of concentration. Thus it appears that carbonic acid, though exercising 
a powerful sedative influence upon the tissues, and paralysing for the time 
their vital energies, so as to give rise to intense inflammatory congestion, yet, 
even after a very protracted action, leaves them in a state susceptible of speedy 
recovery. 

Here we see for the first time a satisfactory solution of the much-debated 
problem of the cause of congestion of the lungs in asphyxia; for there can, 
I conceive, be no doubt that the pulmonary tissues, exposed under ordinary 
circumstances to the influence of a free supply of oxygen, suffer, like those of 
the frog’s web, from the vicinity of an abnormal proportion of carbonic acid, 
and inflammatory congestion is the necessary consequence. At the same time, 
the rapid recovery of the lungs from asphyxial congestion of considerable dura- 
tion, when the normal atmosphere is readmitted, finds an equally close parallel 
in the speedy return both of the pigment-cells and the blood to the healthy 
condition when the foot ot the frog is removed from the aerated water. 

But the most important lesson to be learnt from these simple experiments 
with carbonic acid upon amputated limbs, is that the tissues possess, indepen- 
dently of the central organs of the nervous system, or of the circulation, or even 
of the presence of blood within the vessels, an intrinsic power of recovery from 
irritation, when it has not been carried beyond a certain point; a principle of 
fundamental importance, which has never before, so far as I am aware, been 


+ This observation was made subsequently to the reading of the paper. 
LISTER ! ) 


258 ON THE EARLY STAGES OF INFLAMMATION 


established or conjectured. It applies equally in the case of other irritants. 
Thus having transmitted for about a quarter of a minute, through one of the 
webs of a dark amputated limb, powerful galvanic currents, such as I had before 
ascertained to cause stagnation of the blood when operating for an instant 
upon the living animal, I found, after the lapse of an hour and a quarter, that the 
process of concentration had advanced considerably in the next web, but in 
that on which the galvanism had acted had only just commenced, even in the 
parts most remote from the point to which the poles of the battery were applied ; 
while in the vicinity of that spot the state of full diffusion still continued. After 
the lapse of three more hours, however, the pigment was almost fully concen- 
trated in the part of the web where it was before only slightly so; and even 
where it had been most directly subjected to the galvanic influence, it had 
undergone a certain, though very slight degree of the same change, the chro- 
matophorous cells having even there partially recovered their functions. 

This inherent power in the tissues of recovering from the effects of irrita- 
tion, explains the occurrence of resolution in an amputated limb, such as I once 
observed in a case where a moderate amount of congestion had been induced 
under the action of oil of turpentine before the animal was killed, and the blood 
resumed to a great extent its normal characters in the vessels several hours after 
the limb had been severed from the body. 

The return of the blood along with the tissues to the state of health is a very 
interesting circumstance. Whether it depends upon an intrinsic power of 
recovery on the part of the vital fluid, or on the living solids resuming an active 
operation upon it, is at present uncertain ; but in the meantime, the phenomena 
of resolution already assume a far more intelligible aspect than heretofore, on 
the hypothesis that the tissues generally are endowed with the same faculty of 
self-restoration as the pigment-cells. 

It may be well to give here a list of all the agents whose effects upon the 
pigmentary functions I have investigated. They are as follows: Mechanical 
violence, the galvanic shock, desiccation of the tissues,! dry heat, warm water at 
100° Fahr., intense cold, caustic ammonia, a strong solution of common salt, 
carbonic acid, acetic acid, tincture of iodine, chloroform, oil of turpentine, 
mustard, tincture of cantharides, and croton oil. 

These are all of them irritants, i.e. give rise to inflammatory congestion 
through their direct action upon a vascular part, as I have witnessed in the 
{rog’s web in every case except that of cold, the influence of which in causing 


' The effects of deficiency of moisture in the web were observed in amputated limbs, in which I have 
seen both suspension of pigmentary functions from this cause and recovery from that state after the 
application of water. While the circulation is going on in the living animal I have not found desiccation 
of the web to occur, unless the tissues had been weakened more or less by irritation. 


=. SSS 


ON THE EARLY STAGES OF INFLAMMATION 259 


intense inflammation in the human subject is, however, familiar to all. All of 
them also afforded, in their effects upon the pigment-cells, ocular evidence of 
impairment of the functional activity of the tissues on which they act; and 
considering the number included in the list, and their great variety in essential 
nature, we need not hesitate to admit that similar effects are produced by the 
entire class of irritants. 

There is another tissue in the frog’s web which discharges functions apparent 
to the eye, viz. the arterial muscular fibre-cells, the contractions of which are 
readily recognized in consequence of the changes of calibre which they produce 
in the vessels ; and the manner in which the arteries are affected in a congested 
part of the web indicates that the muscular, like the pigmentary tissue, has 
its functional activity impaired by a certain amount of irritation. Thus I have 
repeatedly been struck with the fact, and noted it before I knew its significance, 
that an artery running through a limited area on which an irritant has acted, 
remains dilated in the spot, although it may vary in other parts of its course. 
This I have observed in one experiment with mustard, in one with acetic acid, 
in two with ammonia, and in one with heat. In the last-mentioned case the 
appearance was particularly striking, from the circumstance that two arteries 
happened to pass through the burnt part, and were constricted to absolute 
closure in the rest of their course, contrasting strongly with their fully dilated 
state within the area. 

In the ammonia experiments also the artery concerned was, in the progress 
of each case, seen to be completely constricted beyond the congested area, 
though still dilated within it. The limitation of this effect on the arteries, to 
the extent of the part acted on by the irritant, proves that it is the result of 
its direct action on the tissues ; differing remarkably in this respect from the 
dilatation of the vessels, which is produced indirectly through the medium of 
the nervous system, and affects a wide space round about the spot irritated. 

But with regard to both the muscular fibre-cells of the arteries and the 
pigment-cells, it may fairly be questioned whether the diminution of power to 
act resides in them or in those portions of their nerves which are situated in the 
irritated region. The view that the nerves are paralysed by irritants is con- 
sistent with the benumbing influence well known to be exerted upon the human 
skin or mucous membranes by some of those agents, e.g. mechanical violence, 
the galvanic shock, cold, and chloroform. I have also observed, as before 

* The only experiment which I made with cold was performed by introducing a test-tube, contain- 
ing a dark amputated limb, into a freezing mixture of ice and salt at about 20° Fahr. for ten minutes. 
When the frozen limb had thawed, I ascertained, on microscopic examination, that the pigment had 


undergone a slight degree of post mortem concentration, but five hours later it was still in much the 
same condition. 


52 


260 ON THE EARLY STAGES OF INFLAMMATION 


alluded to,! that mustard produces a similar result on the cutaneous sensory 
nerves, and hence it seems probable that the same is true of the whole class of 
irritants. Again, the diffusion induced by mustard, croton oil, and cantharides 
indicates, according to what we have seen to be its most probable explanation, 
that the nerves of the pigment-cells suffer impairment of functional activity 
under the action of these three substances. On the other hand, the fact that 
diffusion is arrested equally with concentration by most irritants, appears to 
prove that the chromatophorous cells are themselves also affected with loss 
of power ; for, as has been before alluded to, the withdrawal of nervous influence 
from them in a healthy state of the tissues invariably gives rise to diffusion, 
and the same result would necessarily follow the action of an irritant which 
merely paralysed the nerves. I have also observed, on two occasions, after the 
energetic operation of an irritant upon a part of a web containing a large artery,” 
that drawing the point of a needle firmly across the vessel failed to induce the 
slightest contraction in it, even at the very point crossed by the needle ; proving 
that the muscular fibre-cells had lost their irritability. At the same time it is 
by no means improbable that the nerves of the arteries may suffer before their 
muscular constituents, just as in the intestines, after death, the functions of 
the intrinsic nervous apparatus are lost some time before muscular contractility 
ceases.” 

The question whether the suspension of function induced by irritants is 
confined to the nerves or affects the tissues generally, being one of great interest, 
I was anxious to obtain clear evidence regarding it; and it occurred to me 
that valuable information would probably be derived from observing the effects 
of such agents upon the action of the cilia, which, though not present in the 
web of the frog, exist in abundance upon the mucous surfaces of the mouth and 
oesophagus of that animal. Dr. Sharpey, in his celebrated article ‘ Cilia’ in 
the Cyclopaedia of Anatomy and Physiology, mentions experiments made by 
Purkinje and Valentin, and also by himself, with a great variety of substances, 
including among the rest some irritants, which, when applied with sufficient 
energy, arrested completely, by their chemical action as it was supposed, the 

* See p. 2394. 

* The main arteries lying between the layers of skin of which the web consists, are not so speedily 
acted upon by irritants as the capillaries of the dermis. This is most marked in large frogs with thick 
webs. In one such specimen, a drop of chloroform caused first stagnation and then discoloration from 
chemical action on the blood in the capillaries of the dorsal layer of the web to which it was applied, 
while a main artery lying beneath still contained blood of natural appearance, and showed evidence of 
Janguid contractility, while in the capillaries of the plantar layer of the web, the circulation was still 
going on in a pretty healthy state. This frog, however, seemed endowed with unusual powers of vitality 
in the tissues. This observation, as well as that in the text to which this note refers, was made subse- 


quently to the reading of the paper. 
* See the paper ‘ On the Functions of the Visceral Nerves ’, before referred to (p. 87 of this volume). 


ON THE EARLY STAGES OF INFLAMMATION 261 


movements of the lashing filaments. It is evident, however, that in order to 
produce effects at all comparable to the state of the tissues of the frog’s web 
in congestion, it would be necessary to adopt some more delicate method of 
experimenting, and the most eligible means for this purpose seemed to be to 
allow an irritating vapour to play upon a ciliated surface. Accordingly, on 
the 30th of November, 1857,' having cut off a small piece of the tongue of a frog 
killed about an hour before, and placed it upona slip of glass under the micro- 
scope, with just enough water to permit the free play of the cilia, I held near to it 
a piece of lint soaked in chloroform, keeping my eye over the microscope. The 
effect was instantaneous cessation of the previously rapid action of the cilia, 
which now stood out straight and motionless, like the hairs of a brush. I now 
immediately withdrew the lint, after which the same state of complete inaction 
continued for about half a minute, when languid movements began to show 
themselves, and after the lapse of five minutes more the ciliary action was going 
on pretty briskly in some parts, and ten minutes later seemed to have almost 
completely recovered. 

Thus chloroform vapour produced in the ciliated epithelium-cells a con- 
dition precisely similar to that brought about in the pigment-cells by irritants 
applied so as to cause inflammatory congestion of the web, viz. a state of sus- 
pension or temporary deprivation of functional activity. And as the removal 
of the epithelium-cells from the surface on which they grow does not arrest the 
movements of their cilia, no mere paralysis of nerves could account for this 
result, which necessarily implied that the epithelial tissue itself was affected 
with loss of power to discharge its accustomed functions. In repetitions of 
this procedure upon the same and other portions of the tongue, I did not 
generally get complete cessation of movement of all the cilia, but usually some 
retained a languid action, which improved after the chloroform had been re- 
moved. In one instance, however, the same perfect stoppage took place as in 
the first case, and the recovery was also very general, though the returning 
action was languid. Under these circumstances, a piece of lint dipped in 
strongest liquor ammoniae was brought within about 14 inches of the object, 
and retained there for about fifty seconds, during which time the ciliary motion 
became progressively and greatly diminished, and within twenty-five seconds 
of the removal of the lint, had ceased altogether. Some water was then added, 
so as to get rid of the absorbed alkali, when the cilia soon began to move again, 
and within about three minutes their play was more vigorous and general than 
before. the ammonia was used, and three minutes later it was universal, as it 
was prior to the application of the chloroform. On another occasion, in a 


' This date indicates that the experiments on the cilia have been performed since the paper was read. 


262 ON THE EARLY STAGES OF INFLAMMATION 


different animal, the cilia having been ascertained to be in rapid motion on 
a fresh piece of tongue, lint containing liquor ammoniae was held at a short 
distance from it for thirty-three seconds. The cilia very soon grew languid, 
and by the end of the time mentioned had quite ceased to act. The lint was 
at once withdrawn, but no recovery occurred; the operation of the irritant 
had been rather too energetic, and the vitality of the tissue had been destroyed. 
A languid state of the cilia was also produced by placing freshly prepared 
mustard near them, and improvement took place when it had been removed ; 
but the essential oil itself, applied on lint like the chloroform and ammonia, 
though not acting so rapidly as might have been expected, permanently arrested 
the vibratile filaments. The vapour of strong acetic acid, if acting for four 
seconds, caused great diminution of the motion, and in another instance arrested 
it completely in five seconds. I did not, however, see any recovery from the 
effects of this agent, which produced obvious organic injury in the cells. The 
introduction of a portion of the mucous membrane of the mouth into a bottle 
of aerated water for about twenty minutes gave rise to permanent stoppage 
of the cilia, and similar treatment for three or four hours caused disorganization 
of the epithelium, whereas the same period of immersion in ordinary water did not 
arrest the cilia. Powerful interrupted galvanic currents, transmitted for a few 
seconds through a particular spot in a piece of tongue on which the cilia were 
in free movement, abraded a portion of the epithelium there, and arrested 
completely the cilia of adjacent cells still 7m situ, and rendered those of other 
parts of the specimen extremely languid in their action. But the most satis- 
factory results were obtained from experiments with heat, which has the great 
advantage over chemical irritants, that it leaves no material behind it to act 
upon the delicate tissue. On the 14th of December, 1857, having ascertained that 
steeping a piece of the tongue of a frog for five minutes in water of 110° Fahr. 
caused total and permanent cessation of ciliary action and desquamation of 
the epithelium, at g 9™ p.m. I placed a portion of that organ, in which the 
vibratile movements were equable though rather languid, in water at 100° Fahr., 
and retained it there for a minute and a quarter, when it was transferred to 
cold water. On examining it after the lapse of nearly two minutes, I found 
the cilia acting decidedly more briskly than at first, but in the course of the 
next quarter of an hour they flagged very much, and in many parts ceased to 
move altogether. By this time I had fixed the specimen securely at the bottom 
of a glass trough, which I now suddenly filled up with water at ro2° Fahr., 
and on first catching sight of the object, within a quarter of a minute of this 
procedure, found all the cilia absolutely motionless. I then at once drew off 
the warm water with a siphon previously arranged; and no sooner had this 


ON THE EARLY STAGES OF INFLAMMATION 263 


been done, than movements already began to show themselves in the cilia, 
and their action increased rapidly on my filling up the trough with cold water, 
and in a short time was all but universal and brisk, far superior to what it was 
before the hot water was put in. After a few minutes more, however, it was 
again very languid, and ceased entirely in many parts. I now, at g! 38™, filled 
up the trough with water at 104° Fahr.: at gh 38™ 17s the cilia were almost 
all motionless ; by g 38™ 55s the trough had been again emptied, but at 
gh 39™ 58 there was even less movement seen. Cold water was again poured 
in at gh 39™ 358, and after eighteen seconds, action was reappearing in the cilia, 
and it continued to increase during the next seven minutes, at the end of which 
time it was again almost universal. At gt 52™ the cold water was drawn off, 
and the same condition of the cilia having been ascertained to exist, the trough 
was, at gh 52™ 278, filled up again with water at 104° Fahr.; eighteen seconds 
after this had been done, the ciliary action was found much diminished, but 
had not fully ceased; and after nine seconds more, during which the warm 
water was drawn off, the cilia were still acting very slightly. Within twenty- 
three seconds of this time the trough was again filled with cold water: now, 
however, the epithelium was in many parts beginning to exfoliate, swelling up 
by endosmose in obedience to the ordinary laws of chemical affinity, and so 
indicating that it was losing its vitality. I also lost sight of the precise spot 
which I had been observing, but noticed that ciliary action was again going 
on pretty quickly in some places. There can be no doubt, although there was 
no opportunity for observing the fact, that the first immersion in hot water 
caused cessation of the ciliary action; and that being admitted, we have in 
this case suspension of function and recovery four times repeated in the same 
fragment of tissue in consequence of as many applications and withdrawals 
of the irritant: It is a curious circumstance that each recovery, except the 
final one, brought up the action of the cilia for a time to a better state than 
they had just before the last introduction of warm water. But the discussion 
of this and other circumstances in this case will be best reserved till after the 
mention of another set of experiments. 

In order to eliminate the nerves completely from among the causes both of 
the suspension of function produced by irritants and the recovery from that 
state, it seemed desirable, if possible, to observe those occurrences in detached 
epithelium-cells, and on the 22nd of January, 1859, I made the attempt to do so. 
At first, however, it proved more difficult than I had anticipated. It was of 
course easy to obtain the material to operate on, by gently scraping the surface 
of the palate of a recently killed frog with a knife, and placing the mucus-like 
product on a plate of glass with a drop of water. But the tissue thus separated 


264 ON THE EARLY STAGES OF INFLAMMATION 


from its connexions was in an exceedingly delicate condition, and any agent used 
for arresting the action of the cilia was very apt to destroy at the same time 
the vitality of the cells. Thus when the object was warmed by placing the 
glass plate on a piece of iron at about 100° Fahr. for half a minute, the vibratory 
movements were arrested, but never recovered, and in a short time the cells 
swelled up by endosmose. It appeared probable that the tissue had suffered 
during the time required for the cooling of the glass: and in order to avoid 
this, and also prevent the object-glass becoming obscured by vapour from the 
warm water condensing upon it, the epithelium was placed between two slips of 
thin covering glass, kept from too close approximation by fragments of the 
same material interposed, the whole forming a layer so thin that it would be 
rapidly heated if any hot body were placed in its vicinity, and cooled as quickly 
on its removal. A small cautery iron, with a bulbous extremity about as big 
as a hazel-nut, just too hot to bear in contact with the finger, was now put 
behind the stage of the microscope, within about three-quarters of an inch of 
the object, the diaphragm plate having been removed to afford room for this 
being done without interfering with the light sent up by the reflector. The 
result, which I watched from the first, was the same that I had once before 
observed from the very gentle application of heat to a portion of a frog’s tongue, 
viz. primary increase in the action of the cilia which had previously been languid,* 
but which, within ten seconds of the approximation of the cautery, were moving 
with great rapidity, and continued to do so for about twenty-five seconds, at 
the expiration of which their motion was seen to be diminishing, and after 
another minute and a half it was considerably more languid than at the beginning 
of the experiment. The cautery being now removed was found to be much 
cooled though still warm, and its withdrawal did not affect the cilia, which still 
remained much in the same state after the lapse of eight minutes. I now 
repeated the experiment upon a fresh portion of epithelium, but this time used 
the cautery red hot, placing it about 2 inches behind the object : no sooner 
had this been done than the action of the cilia became excessively increased, 
but this did not continue for more than five seconds, when they became per- 
fectly motionless. The hot iron was now at once withdrawn, but the cilia 
under special observation did not recover. In other situations in the same 
specimen, however, movements were observed in the course of the following 
minute, and it was still continuing seven minutes later, when a part having 

‘ Professor Weber, of Leipsig, observed several years ago that the action of cilia upon epithelium 
cells removed from the human nostril was increased by gentle warmth, but retarded by cold. In that 
case the elevated temperature was natural to the tissue, and might be supposed to operate by restoring 


it to its normal conditions. In the cold-blooded reptile, however, the accelerated movement under 
the influence of heat has, of course, a very different significance. 


ON THE EARLY STAGES OF INFLAMMATION 265 


been brought into the field where there were two considerable groups of cells 
in moderate activity, the cautery was again applied at a distance of about 
24 inches. The motions of the cilia immediately became distinctly increased, 
but, as in the former case, this condition gave place in five seconds to universal 
quiescence. The iron was then removed, and on re-examination after three 
minutes, the cilia were again moving, though in a somewhat languid manner 
in both parts of the field. For the sake of confirmation I again operated in 
a similar manner upon another specimen, on which I performed no less than 
five successive experiments with similar results in all. In the first three of 
these trials I had the very same cilia under observation, and saw them time 
after time become first increased in action and then arrested under the influence 
of the cautery, and gradually recover after its removal. In some instances the 
times of cessation and of recovery were noted as follows :—In the first the 
cilia were arrested in two seconds after the application of the hot iron, but 
the exact time of recovery was not observed ; in the second, cessation of move- 
ment was produced in two seconds, and return began in fifteen seconds ; in 
the third, cessation was in fifteen seconds, and recovery also in fifteen seconds ; 
in the fourth, the times were not noted ; in the fifth, movement ceased in about 
two seconds and returned in twenty. The experiments were performed within 
about five minutes of each other, or something less. It is also to be remarked, 
that there were some slight differences in the degree of heat of the cautery 
and its vicinity to the object. 

These experiments are as instructive as they are simple and easy of per- 
formance. They show conclusively that a component tissue of the animal 
frame may, independently of the nervous system, have its actions either excited 
or paralysed by the direct operation of an irritant upon it, and that it may 
possess an equally independent power of recovery. Also in the accelerated 
movements of the cilia elicited by very gentle heat, as compared with the cessa- 
tion of their vibrations under a higher temperature, we have a striking con- 
firmation of the view which I had taken of the relaxation of the arteries and 
hollow viscera in consequence of nervous irritation.! For the law which we 
thus see regulating the effects of heat upon the epithelium-cells is precisely that 
which I had inferred must govern the action of afferent nerves upon nerve- 
cells ; this law being, that an agency which, when operating mildly, stimulates 
a tissue to increased activity, may, when more energetic, temporarily arrest 
its functions. Whether or not the converse always holds, viz. that any agent 
which is capable of suspending the functional activity of a tissue may also 
excite it if applied with sufficient gentleness, or, in other words, whether irritants 


' Vide antea, p. 232. 


266 ON THE EARLY STAGES OF INFLAMMATION 


are in all cases also stimulants, seems very doubtful. As regards the nerves, 
such does appear to be the case; for while many, and probably all influences 
which induce inflammatory congestion cause temporary paralysis of sensation 
in parts on which they act severely enough, they all stimulate the afferent 
nerves in the first instance, as is shown by the reflex changes in the calibre of 
the arteries which occur round about any irritated spot. The nervous centres, 
too, present an illustration of the same principle, not only in the effects pro- 
duced upon them by the nerves, as lately alluded to, but also in the excitement 
well known to be occasioned by small doses of many sedative narcotics, such 
as alcohol, opium, and chloroform, which may be regarded as special irritants 
of the nervous centres. In the case of the cilia, I have not observed primary 
increase of movement to be induced by any agent besides heat ; but I am not 
prepared to say that it might not by careful management be made to occur 
with some other irritants. 

The pigment-cells in the common frog give very little indication of the 
stimulating properties of irritants, as is evident from several of the experiments 
which have been recorded in this section. In the tree-frog, however, as we are 
informed by the German authorities, a part of the integument subjected to such 
influences rapidly assumes a pale tint, and that even in a portion of skin removed 
from the body. I have also several times noticed, after pinching the web of 
a common frog, that, although in the spot actually squeezed, the pigment-cells 
were deprived of their power of changing, a pale ring about one-sixteenth of an 
inch in breadth has gradually formed in its immediate vicinity in the course 
of the next hour; whence it seems probable that direct irritation tends to 
excite concentration in the English species as well as in the continental, but 
that in the former the effect is developed much more slowly, so that it is apt 
to pass unnoticed. I further, on one occasion, saw post mortem concentration 
greatly accelerated by heat.1 It is doubtful, however, whether these results 
are due to direct action upon the pigment-cells ; for in the tree-frog, as well 

‘ This observation was made as follows :—On the 2nd of December, 1857, having amputated the legs of 
a dark frog, I put them both into water of 100° Fahr., but removed the left limb within six minutes 
of its immersion and placed it in cold water, leaving the right for a quarter of an hour longer, at the 
end of which time it was considerably paler than the left, and the microscope showed that its pigment 
was more concentrated. But while the warm water had accelerated the process of concentration up 
to a certain point, it had ultimately paralysed the pigment-cells and rendered them incapable of further 
change; so that the right limb remained permanently of the same colour as when removed from it, 
whereas in the left, which had been subjected for a much shorter time to the noxious agency, concentra- 
tion continued to advance, so that in twenty-five minutes that leg was as pale as the other, and after 
an hour more it was a good deal the lighter of the two. I may further mention that rigor mortis was 
already carried to the extreme degree in the muscles of the right limb when taken out of the water, 
but in the left this change did not commence till about twelve hours later. At this period the pigment 


in the left limb still showed signs of retaining its functions, while that in the right had a dirty, indistinct 
appearance, indicating that it had lost its vitality. 


ON THE EARLY STAGES OF INFLAMMATION 267 


as in the English kind, the pale tint was not confined to the precise spot operated 
on, but affected a limited area of surrounding tissue ; whence it seems likely 
that it is developed through the medium of a local nervous apparatus contained 
in the skin.’ If this be true, we have no proof that the pigment-cells are capable 
of being stimulated except by nervous influence, although they are, as we have 
seen, peculiarly susceptible of suspension of function through the direct operation 
of irritants upon them. 

With regard to the nature of the change experienced by the tissues when 
temporarily deprived of power by irritants, the primary increase of motion 
of the cilia, lapsing into quiescence, under the operation of heat, may suggest 
the idea of exertion followed by exhaustion. But that the state of incapacity 
is not dependent on previous action, seems clear from the fact that in the pig- 
ment-cells it is maintained and aggravated by an irritant continuing in operation 
after complete suspension of function has been induced, the same kind of effect 
being still produced upon the tissues which are unable to act as upon healthy 
parts. As an illustration of this, I may revert to the results of immersion of an 
amputated limb in aerated water. The carbonic acid, as we have seen, entirely 
prevents the occurrence of post mortem concentration, implying that the powers 
of the chromatophorous cells are completely suspended by it within a few 
minutes at most of its first acting on the part ; yet, however long the tissues 
thus paralysed are kept subjected to its influence, they remain without any 
sign of action. They will, however, recover speedily and completely if soon 
taken out and exposed to the air, so that the irritating gas may be dissipated ; 
whereas if retained for several hours in the aerated water, they may, indeed, 
have their powers restored to a certain extent on removal from it, but exhibit 
only very feeble action. Such facts as these prove conclusively that the tissues 
may have their functional activity impaired without loss of vitality by the direct 
action of irritants, independently of any stimulating effects which may be at 
first produced by them ; and also that the influence thus exerted is of an in- 
jurious tendency. 

The imperceptible transition from suspension of function to loss of vitality 
displayed by the long-continued operation of carbonic acid upon the pigment- 
cells is also well illustrated by some of the experiments upon the cilia, especially 
those with heat and ammonia, which, unless employed with extreme caution, 
not only permanently arrested the vibratile filaments, but reduced the epithelium- 
cells to a condition in which they were amenable to the ordinary laws of chemical 
affinity. All irritants appear to be agents which, if operating with sufficient 
energy, completely destroy vitality, probably by inducing, through chemical 


* See the paper ‘On the Cutaneous Pigmentary System ’, before referred to, p. 48. 


268 ON THE EARLY STAGES OF INFLAMMATION 


or physical action, an irreparable derangement of the molecular constitution 
of the tissues. Their essential property, however, is that of causing, when 
applied somewhat more mildly, a minor degree of disturbance or disorder in the 
component textures of the body, which are rendered for the time being unfit 
for discharging their wonted functions,! though afterwards, by virtue of their 
innate powers, capable of spontaneous recovery, the rapidity and completeness 
of which bears an inverse ratio to the intensity and duration of the previous 
irritation. Lastly, these same noxious agents, if in a still more gentle form, 
operate, upon some of the tissues at least, as stimulants, rousing them to in- 
creased exertion of their vital functions. How this effect is brought about must 
I believe, be only matter of uncertain speculation, so long as the real nature of 
life in the animal frame remains, as it probably ever will remain to our finite 
capacities, an impenetrable mystery. 

It is an interesting circumstance that, in the experiments with warm water, 
the cilia, after recovering from the state of quiescence, moved for a while more 
briskly than they did immediately before the application was made. This 
increased action cannot be attributed, like the primary acceleration resulting 
from very gentle warmth, to a mild operation of the irritant ; for the epithelium- 
cells must have been completely cooled down before it commenced. It must 
therefore be regarded as a true reaction on the part of the tissue, whether depen- 
dent on accumulation of vital energy during the period of suspended function, 
or excited, as by an irritant, by the state of disorder which the warm water 
had induced, seems uncertain. 

Considering the number and variety of the functions which direct observa- 
tion has shown to be suspended by irritants, viz. pigmentary concentration and 
diffusion, ciliary motion and nervous action, it appears probable that all the 
vital processes are liable to similar temporary arrest. 

Different tissues, however, seem to differ in the facility with which they 
are affected by irritants. The pigment-cells are very susceptible to their influence 
as is indicated by the complete paralysis which we have seen to be produced in 
them by agencies that give rise to only a minor degree of inflammatory con- 
gestion ; and also by the circumstance which I have often observed in the web 
of the frog, that, as in the choroid coat of the human eye, they become absorbed 
in parts which have been injured, having been deprived of vitality by causes 
which inflicted on other textures only a recoverable lesion. The epithelium- 
cells, too, are very sensitive to irritation, exhibiting its results more rapidly 
than can be accounted for merely by their exposed situation. In those which 


* The word ‘irritant’ is etymologically ill adapted to express the possession of this property ; 
but as it is universally employed in professional nomenclature, it is perhaps best to continue to use it. 


ON THE eAKLY STAGES OF INFLAMMATION 269 


invest the mucous membrane of the mouth, the cilia with which they are pro- 
vided furnish the opportunity of which we have availed ourselves, of observing 
the stage of suspension of function in consequence of very gentle treatment ; 
and though the epidermis does not admit of this, it shows the further stage of 
loss of vitality by exfoliating after an amount of injury from which the imme- 
diately subjacent tissues readily recover. John Hunter was unquestionably 
correct in the opinion that the elevation of the cuticle in vesication depends 
not only on the effusion of serum beneath it, but on a primary separation arising 
‘from a degree of weakness approaching to a kind of death in the connexion 
between the cuticle and cutis’ For I find that in an amputated limb free 
from blood, although no effusion of serum can occur, the epidermis becomes 
speedily loosened in a part to which an irritant is applied, as for example, in 
a web treated with oil of turpentine, whereas it remains elsewhere firmly attached 
for days if the weather be cool. 

The temporary abolition of the normal relations between the blood and the 
tissues in inflammatory congestion,” must be added to the list of instances of 
suspension of vital properties by irritation. The tissues the healthy state of 
which seems most likely to be essential to that of the vital fluid, are those con- 
tiguous to it, viz. the walls of the blood-vessels ; and that these are really 
deprived of their vital endowments during inflammation, seems implied by the 
character of the material which is transmitted through them in that condition. 
For we have seen that the vascular parietes differ, in the state of health, from 
all ordinary solids in being destitute of any attraction for the fibrine, if not 
positively repelling it,? and that this is probably the cause of the merely serous 
character of the effusion which takes place in mechanical dropsy depending 
upon abnormal pressure of the blood within healthy vessels. On the other hand, 
the exudation of the liquor sanguinis in its integrity, such as occurs in severe 
inflammation, cannot, I think, be satisfactorily explained by the mere abnormal 
pressure of the blood produced by dilatation of the arteries and concomitant 
obstruction in the capillaries ; but seems naturally accounted for on the hypo- 
thesis that the walls of the vessels, like other tissues, lose, for the time, in inflam- 
mation, their vital properties, and, acquiring an attraction for the fibrine like 
that exercised by ordinary solids, permit it to pass without opposition through 
their porous parietes. 

It may be well to present a brief summary of the principal results arrived 
at in the present section. 

It appears that the various physical and chemical agents which, when 


1 Works of John Hunter, Palmer’s edition, vol. 111, p. 340. 
* See close of last section. * Vide antea, p. 241. 


270 ON THE EARLY STAGES OF INFLAMMATION 


operating powerfully, extinguish the life of the constituents of the animal body, 
produce by a somewhat gentler action a condition bordering upon loss of vitality, 
but quite distinct from it, in which the tissues are, for the time being, incapaci- 
tated for discharging their wonted offices, though retaining the faculty of returning 
afterwards, by virtue of their own inherent powers, to their former state of 
activity, provided the irritation have not been too severe or protracted. This 
suspension of function or temporary abolition of vital energy is the primary 
lesion in inflammatory congestion ; the blood in the vicinity of the disabled tissues 
assuming the same characters as when in contact with ordinary solid matter, 
and thus becoming unfit for transmission through the vessels ; while the return 
of the living solids to their usual active state is accompanied by a restoration 
of the vital fluid to the healthy characters which adapt it for circulation. 


CONCLUSION 


It remains to glance at the application of the principles established in the 
preceding pages to human pathology. 

The post mortem appearance which is universally admitted to indicate 
that the early stages of inflammation have occurred during life, is intense redness, 
depending essentially not upon peculiar distension of the vessels with blood, 
but upon abnormal accumulation of the red corpuscles in their minutest rami- 
fications. A beautiful example of this condition, developed idiopathically, was 
presented by the case of incipient meningitis mentioned in the Introduction, 
in which the vessels of an affected spot of pia mater were filled with a crimson 
mass of confusedly compacted corpuscles, exactly as in an area of the frog’s 
web to which mustard has been applied. The derangement of the vital fluid 
in the human subject being thus closely parallel to that which we have studied 
in the batrachian reptile, we can hardly doubt that in the former, as in the 
latter, the living solids are in a state of more or less complete suspension of 
functional activity during inflammatory congestion. This view is supported by 
the effusion of liquor sanguinis in its integrity in the more advanced stages of 
the disease in man, and by the speedy coagulation of fibrine upon inflamed 
serous surfaces, or in the interior of vessels affected with arteritis or phlebitis. 
For these circumstances, as has been before remarked, appear to indicate that 
the tissues are for the time being reduced still more towards the condition of 
ordinary solid matter. These arguments, derived from the appearances of the 
blood, are further corroborated by the immediate transition which is apt to 
occur from intense human inflammation to gangrene.! 


* The degenerations of tissue which result from inflammation, ably delineated by Mr. Paget in his 
Lectures on Surgical Pathology, are additional evidence in the same direction. 


ON THEIPBPARLY STAGES OF INFLAMMATION 7g fs 


But a comprehensive and complete account of the inflammatory process 
must embrace not merely the state to which the tissues are brought when the 
disease is fairly established, but also the causes which lead to it. 

Inflammation is sometimes brought about in man in a way strictly analogous 
to that in which we induce it in the web of the frog’s foot, viz. by the immediate 
operation of some noxious agent from without, as when boiling water is poured 
upon the skin. One peculiarity connected with such cases, as compared with 
those which are of idiopathic origin, is the great rapidity with which the various 
stages of the disorder are often developed. This, however, is the natural con- 
sequence of the direct manner in which the prejudicial influence is exerted 
upon the tissues ; the inflammatory phenomena supervening more speedily in 
proportion to the energy of the irritant. This principle is well illustrated by 
the effects of mechanical violence upon the human integument. A moderate 
degree of pressure applied continuously gives rise, during the first few hours, 
to nothing more than inflammatory congestion, which disappears soon after the 
pressure has been removed, as seen in the red mark produced upon the forehead 
by a tightly fitting hat. But if such treatment be continued for a considerably 
longer period, vesication will result, as when apparatus employed for the treat- 
ment of fractures is applied too firmly for many hours together over a bony 
prominence. The same effect which is thus slowly developed under a moderate 
degree of mechanical irritation, may, however, be induced very rapidly through 
the same agency in a more intense form, as is shown by the bullae which are 
often observed in surgical practice very soon after the infliction of a severe 
contusion. Here the source of irritation being no longer in operation, there is 
no blush of redness in the vicinity dependent upon arterial dilatation, and hence 
such cases are often supposed to have nothing in common with inflammation ; 
and I have known these vesicles mistaken for evidence of gangrene, so as to 
lead to unnecessary amputation. The suddenness with which inflammatory 
oedema arises in consequence of the bites or stings of venomous reptiles is ex- 
plicable on the same principle. The poison appears to diffuse itself among 
the tissues so as to operate directly upon them, and when extremely virulent, 
kills them outright ; but when less potent, produces merely a temporary though 
rapid prostration of their vital energies with consequent inflammatory effusion. 
Again, the congestion of the lungs, which comes on so quickly in asphyxia, has 
been before alluded to’ as probably the result of the sedative influence which, 
from experiments upon the frog, we are led to believe must be produced upon 
the pulmonary tissue by the abnormal amount of carbonic acid in the air-cells. 

In the class of cases hitherto considered, the derangement of the part, 


1 ae 
Seep. 257. 


272 ON THE EARLY STAGES OF INFLAMMATION 


and the causes which lead to it, being both, to a considerable extent, understood, 
the disease may, I think, be regarded as in so far satisfactorily explained. But 
one important lesson taught by the results of this investigation is, that it is 
necessary to draw a broad line of demarcation between inflammation produced 
by direct irritation, and that which is developed indirectly through the medium 
of the nervous system, whether in the immediate vicinity of a source of irrita- 
tion, as around a tight stitch in the skin, or a thorn in the finger, or at a distance 
from the disturbing cause, as when the kidneys are affected in consequence 
of the passing of a bougie, or the lungs through exposure of the feet to cold. 
Nothing can better illustrate the importance of this distinction, than what takes 
place in a recent wound. In consequence of the injury inflicted by the knife, 
together with the subsequent manipulation and exposure, the tissues, in a thin 
layer at the cut surface, are thrown into that condition which leads to effusion 
of liquor sanguinis, the fibrine of which, speedily coagulating, remains to con- 
stitute the bond of primary union, while the serum trickling away between the 
lips of the wound produces the discharge which soaks the dressing during the 
first twenty-four hours. But neither during the exudation of the lymph in 
such a case, nor during its subsequent organization, is there necessarily any 
inflammation induced in the lips of the wound through the nervous system ; 
and if this complication does occur, it interferes with the healing process in 
a degree proportioned to its intensity. In other words, while a certain amount 
of inflammation as caused by direct irritation is essential to primary union, any 
degree of it as induced indirectly is both unnecessary and injurious. 

The question how inflammation is developed through the medium of the 
nervous system, possesses a high degree of interest, in consequence of its bearing 
upon the manner in which counter-irritation operates therapeutically. In the 
integument, where we have the opportunity of seeing the affected part, the first 
indication of the supervention of inflammatory disorder around a centre of 
irritation is a blush of redness, which, as before shown,! consists, in the first 
instance, of mere dilatation of the arteries with rapid flow of blood through the 
capillaries. It is quite conceivable that arterial dilatation, carried to an extreme 
degree along with powerful action of the heart,? may so increase the tension 
upon the tissues as to impair their powers gradually by mechanical irritation, 
just as the frontal integument is affected by long-continued gentle pressure 
from without, as above alluded to; for we know that when inflammation does 
exist, mere increase of tension upon the blood in the vessels will greatly aggravate 

St DCe. Pp, ber 

* It is to be observed, that in the frog, when full dilatation of the arteries lasts for days together 


without the production of inflammatory congestion, the state of the vessels has been brought about 
by a very serious operation which greatly weakens the action of the heart. 


~_ 


ON THE EARLY STAGES OF INFLAMMATION 273 


the disorder, as when an inflamed foot is kept in a dependent posture. Sup- 
posing this to be the whole mechanism of the disease, its origin would be suffi- 
ciently intelligible ; for we have seen that vascular dilatation caused by irritation 
operating through the medium of the nervous system appears to depend on 
a depressing influence produced by excessive action of the afferent nerves upon 
the ganglia which preside over the arterial contractions. There are, however, 
some circumstances, such as the dryness of the nostril which may exist in the 
early stages of coryza, and sudden suppression of urine in consequence of 
urethral irritation in cases where renal congestion becomes ultimately estab- 
lished, which seem to indicate that other functions as well as arterial contraction 
may be primarily arrested by nervous agency in the early stages of inflammation. 
The study of the pigmentary system of the frog has afforded proof that other 
tissues besides muscular fibre are under the control of the nerves, and it seems 
not unlikely that gland-cells or other forms of tissue may, like nerve-cells, be 
reduced to a state of inactivity by excessive nervous action ; and thus we seem 
to have a clue to comprehending what at first appears anomalous, that prostra- 
tion of the vital energies of the part actually inflamed may be brought about by 
unusually great activity in the parts of the nervous system specially concerned 
with it. This, however, is a wide subject, which requires further investigation. 
But in the mean time we may, I think, consider as satisfactorily established the 
fundamental principle, that whenever inflammatory congestion, or, in other 
words, that disturbance of the circulation which is truly characteristic of inflam- 
mation, exists in any degree, the tissues of the affected part have experienced 
to a proportionate extent a temporary impairment of functional activity or 
vital energy. 


LISTER 1 Al 


274 ON THE EARLY STAGES OF INFLAMMATION 


PLATE V 


represents the effects produced by irritants upon the pigmentary tissue and the blood-vessels , 
of the frog’s foot. 


Fig. 1 shows the results of the application of mustard to the web. The pigment was at first in the 
stellate condition as on the left-hand side of the sketch, and it remained permanently in that 
state in the part on which the mustard lay, while at the same time intense inflammatory con- 
gestion was produced there, indicated by the deep red colour of the vessels. Just beyond the 
edge of the mustard the irritating vapour of the volatile oil gave rise to full diffusion of the pig- 
ment (an effect peculiar to mustard and a few other irritants when acting mildly), but without 
material inflammatory disorder of the blood ; as seen in the stripe down the middle of the draw- 
ing. During the progress of the case the animal changed to a pale colour in the body generally, 
assuming the dotted aspect depicted on the right-hand side of the sketch in all parts which had 
not been acted on by the mustard, and thus deprived for the time being of the power of concen- 
tration. It will be observed that the blood-vessels of the healthy part are not materially smaller 
than those of the congested region ; the deep colour of the latter being due to their containing 
closely packed red corpuscles, while the former are pale in consequence of the blood within them 
having the normal proportion of colourless liquor sanguinis. 

Fig. 2 illustrates the effects of mechanical violence. The lower half of the sketch represents parts of an 
area in one of the webs of a dark frog, which was pinched with a pair of padded forceps so as to 
give rise to inflammatory congestion. The animal afterwards grew much paler, so that in healthy 
parts the pigment assumed the angular or slightly stellate appearance shown in the upper part 
of the drawing. But on the particular spot on which the mechanical violence had operated, the 
chromatophorous cells being incapable of discharging their usual functions, the pigment remained 
in the fully diffused state in which it was at the commencement of the experiment. 


Plate V 


% 
} 


= wae, ee ¢ 


ne CONTRIBUTION: TO. THE GERM THEORY OF 
PUTREFACTION AND OTHER FERMENTATIVE 
CHANGES, AND TO THE NATURAL HISTORY OF 
TORULAE AND BACTERIA" 


[Transactions of the Royal Society of Edinburgh, vol. xxvii, 1875.] 


PART I 


ALTHOUGH the subject of the following communication has of late years 
attracted a great deal of attention among the public generally, it may, neverthe- 
less, be well for me to preface my statements by a few elementary remarks. 

It is well known that organic substances, when left exposed under ordinary 
circumstances, undergo alterations in their qualities. For example, an infusion 
of malt experiences the alcoholic fermentation ; a basin of paste prepared from 
wheaten flour becomes mouldy; or, again, a piece of meat putrefies when so 
treated. The microscope shows that each of these changes is attended by the 
development of minute organisms. In the fermenting sweet-wort the yeast 
which falls to the bottom of the containing vessel is found to consist of budding 
cells, constituting the yeast plant, Torula Cerevisiae, represented in Plate VI, 
Fig. 22 In the mouldy paste the blue crust which is the most frequent appear- 
ance, owes its colour to the spores of a species of filamentous fungus, Penzczl- 
lium Glaucum, the commonest of all moulds, of which Fig. 1 in Plate VI repre- 
sents a pencil of fructifying threads; and the putrid flesh will be probably 
found teeming with bodies which, in the most typical form, consist of two little 
rods, connected endways as by a joint, such as are seen at a, Fig 3, Plate VI, 
characterized by astonishing powers of locomotion, and, from their rod-like 
form, termed Bacteria. 

The Germ Theory supposes that the organisms are the causes of the changes ; 
that the germs of these minute living things, diffusible in proportion to their 


? This communication was originally made orally to the Royal Society on the 7th of April, 1873. In 
preparing it for the press I have introduced various details which I was unable toenter upon at the time. 
I have also added facts ascertained at subsequent periods; but the dates of the observations being 
always mentioned, there will be no difficulty in distinguishing between those made before and after the 
delivery of the original address. 

* In the present state of uncertainty regarding the true affinities of the yeast plant, it seems justi- 
fiable to retain for it the old name Torula Cerevisiae, a practice which has the advantage of enabling 
us to apply to similar budding cells the generic name Torula, and the adjective toruloid. 


r.-2 


276 ON THE GERM THEORY OF PUTREFACTION 


minuteness, are omnipresent in the world around us, and are sure to gain access 
to any exposed organic substance ; and, having thus reached it, dev lop if it 
prove a favourable nidus, and by their growth determine the chemical changes ; 
and further, that these organisms, minute though they appear to us, form no 
exception to the general law of living beings, that they originate from similar 
beings by parentage. 

Of those who oppose this theory, some attribute the changes to the oxygen 
of the air; others, while convinced of the insufficiency of the oxygen theory, 
hold the doctrine of so-called chemical ferments, and ascribe the alterations we 
are considering to organic principles destitute of vitality, the organisms being 
regarded as accidental accompaniments ; while others, admitting perhaps the 
fermentative agency of the organisms, believe that they do not necessarily 
spring from parents like themselves, but may arise, de novo, from the inorganic 
world by spontaneous generation. 

The philosophical investigations of Pasteur long since made me a convert 
to the Germ Theory, and it was on the basis of that theory that I founded the 
antiseptic treatment of wounds in surgery. The results of the treatment pur- 
sued constantly on this guiding principle have convinced me more and more of 
the truth of the theory upon which it was based ; and if I were to put together 
the facts which I have had presented to me in surgical practice, proceeding on 
the antiseptic system, I should be able to present an array of evidence in favour 
of the Germ Theory as good and convincing as experiments performed in a 
laboratory. 

But whilst I was thus for my own part thoroughly convinced of the truth 
of the Germ Theory of fermentative changes, I was led about a year and a half 
ago to direct my attention again to the subject by a remarkable paper by Dr. 
Burdon Sanderson, which appeared as an appendage to a report by the Medical 
Officer of the Privy Council.t1 Dr. Burdon Sanderson produced evidence, of 
which the following may be taken as a specimen :—If a vessel like a miniature 
ale-glass was heated considerably above the boiling point of water, to destroy 
any organisms adhering to it, and, when cooled sufficiently, was charged with 
boiling Pasteur’s solution—a fluid ingeniously devised by that eminent chemist 
to provide suitable pabulum for organisms, consisting of a solution of cane- 
sugar, some ammoniacal salt, and earthy materials derived from the ashes of 
yeast—the liquid being left freely exposed to the air, fungi developed in it, but 
no bacteria. If, on the other hand, a drop of water, say water from the tap, 
was introduced into the Pasteur’s solution, within a few days the originally 
transparent liquid was rendered milky by the presence of abounding bacteria. 


* This paper will also be found in the Quarterly Journal of Microscopical Science, vol. xi. 1871. 


AND OTHER FERMENTATIVE CHANGES 297, 


Another very remarkable fact is mentioned by Dr. Burdon Sanderson in the 
paper referred to. These bacteria, which have been commonly regarded as 
tough-lived organisms, difficult to kill, were found by him to be deprived of 
vitality altogether by simply drying them thoroughly at a temperature no 
higher than that of an incubator for the hatching of eggs, about 100° Fahr. 

By this second fact he explained the first. If bacteria are deprived of all 
vitality by dryness, then it seemed comprehensible that the dust of the air 
should contain no living bacteria, and, therefore, that none should have grown 
in the Pasteur’s solution exposed to the atmosphere in the experiment first 
mentioned. 

Further, Dr. Sanderson was led to conclude that bacteria were the sole 
causes of putrefaction ; that fungi could only cause mustiness, or a compara- 
tively insignificant alteration in organic substances. 

Now, if these conclusions were strictly correct, they would affect my surgical 
practice in a most important manner. If it were true that the air does not 
contain the causes of putrefaction, then it would not be necessary for me, in 
carrying out the antiseptic system of treatment, to provide an antiseptic atmo- 
sphere. All that would be needful would be to purify the surface of the skin 
of the part to be operated upon by means of some efficient antiseptic, to have 
my own hands, and those of my assistants, and also the instruments, similarly 
purified ; and then the operation might be performed without the antiseptic 
spray which we now use, and no one would rejoice more than myself to be able 
to dispense with it. 

At the same time, striking as Dr. Sanderson’s facts were, I could not believe 
the truth to be exactly as he stated—that ‘no amount of exposure has any 
effect in determining the evolution of microzymes’ (bacteria). Various con- 
siderations, including circumstances that I had witnessed in surgical practice, 
made me fear the news was too good to be true. I determined, therefore, to 
put the matter to the test by a very simple experiment. 

The fluid which I used was urine, which has so often been made the subject 
of experiments by Pasteur and others; but instead of employing boiled urine 
for the purpose, I thought that in all probability the fluid might be obtained 
unboiled, yet uncontaminated, by a very simple procedure. According to a 
principle which I enunciated about two years ago before the Royal Medical 
Society here, and of which I must not now give any more evidence than the 
fact that will immediately follow—the healthy living tissues are capable of pre- 
venting the development of these low organisms in their immediate vicinity. 
If that were true, although undoubtedly the skin in the neighbourhood of the 


1 See Microscopical Journal, vol. xi, p. 338. 


278 ON THE GERM THEORY OF PUTREFACTION 


meatus urinarius must contain such organisms, yet supposing the urethra to be 
in a state of perfect health, the tissue of the lining membrane should prevent 
the entrance of those organisms, even for the thousandth part of an inch, within 
the mucous canal. The urethra, of course, contains putrescible materials, 
whether it be residual urine or the mucus secreted by the lining membrane ; 
and the intervals between acts of micturition would afford time for the organ- 
isms to spread extensively inwards if it were a tube of indifferent matter ; but 
I hoped, in accordance with the principle which I had had reason on other 
grounds to believe in, that the organisms would prove unable to develop in 
this putrescible material, however favourable a nidus for their growth. If this 
were really the case, instead of having the urine drawn off with a catheter, with 
special precautions, as was done by a surgeon at Pasteur’s request, if the skin 
round the orifice of the urethra were treated with an efficient antiseptic, say 
with a solution of carbolic acid in forty parts of water, the urine might then be 
passed from the patient from whom it should be obtained, perfectly uncontami- 
nated, though unboiled, free from any living organisms. Accordingly, on the 
16th of November, 1871, I performed the following experiment :—Six wine-glasses 
were heated far above the temperature of boiling water by means of a spirit- 
lamp. I may here remark that in the rest of this communication, wherever 
I use the word ‘ heated’ (in quotation marks), I shall wish to be understood as 
meaning that the thing spoken of is not hot when used, but that it has been 
heated far above the boiling point of water, and then allowed to cool. Six 
glasses, then, were thus prepared, ‘ heated’ by means of a spirit-lamp. A glass 
plate large enough to cover them all, and overlap them considerably, was also 
similarly ‘heated’. Urine was then passed into these six glasses with the 
antiseptic precaution that I have mentioned. Two of the glasses, before being 
covered, received each a minim of water from the tap ; and into a third a much 
smaller quantity of water was introduced. To the rest no water was added, but 
one was left exposed for twenty-four hours to the air of my study, while the 
other two were put at once under the cover of the glass plate. After the lapse 
of forty-eight hours, quite in accordance with Dr. Sanderson’s statement, the 
two to which the drops of water had been added were turbid from the develop- 
ment of large and active bacteria ; and the one which received a very minute 
quantity of water was similarly affected, though in a less degree, while the other 
glasses showed no change. But when twelve more hours had passed, the glass 


which had been exposed to the air, without the addition of any water, presented 
spots of opacity in the cloud of deposited ‘ mucus ’, and on examining a portion 
of the cloud with the microscope, I found in the first field several bacteria in 


full activity. But the other two which had been covered by the glass plate 


AND OTHER FERMENTATIVE CHANGES 279 


from the first were perfectly clear. I should say that after twenty-four hours 
these glasses, instead of being covered with the glass plate, were put under 
a glass shade common to them all; an exceedingly rude method of experiment- 
ing, merely intended to obtain rough evidence of whether exposure to the air 
would or would not lead to the development of bacteria. Considering, there- 
fore, how imperfect were the means of excluding dust, I was not at all surprised 
to find, in the course of a few days, that the two glasses which had remained 
clear longer than the rest also exhibited organisms of different kinds, into the 
details of which I need not enter further than to say that those of one of the 
glasses included distinct bacteria. 

This experiment, rude as it was, showed clearly that exposure to the air 
might lead to the development of bacteria, provided always that the urine was 
free from contamination to begin with. And, further, the comparative slowness 
of any change in the two glasses which were neither treated with water nor 
intentionally exposed to dust, led me to think that in all probability, if the 
experiment had been performed more rigorously, I should have had no develop- 
ment at all in them; or, in other words, that the method of obtaining uncon- 
taminated urine was really trustworthy. If so, the fact was not only valuable 
as affording a ready means of performing experiments on the question at issue, 
but also exceedingly interesting in itself, as a strong corroboration of the view 
that the healthy living tissues prevent the development of these organisms. 

Accordingly, 1t seemed worth while to perform another similar experiment 
somewhat more rigorously, and this was done on the 21st of November of the 
same year. Wine-glasses were ‘heated’ as before, but each was provided with 
a separate cover, which was also ‘heated’. Two of these covers were inverted 
porcelain evaporating dishes, which had the advantage of preventing the direct 
effect of lateral currents of air; but as [ had only two such dishes at hand, 
I used for the rest of the glasses square pieces of glass plate overlapping well 
in all directions ; anda glass shade was put over allasan additional protection 
from dust. Further, instead of having the urine passed directly into the several 
glasses in succession, which was an inconvenient procedure, I had it introduced, 
in the first instance, into a flask provided with a porcelain cap, the flask having 
been heated over a red fire and allowed to cool under protection of the cap, 
which had also been thoroughly heated. The glasses were then successively 
charged from the flask with as little exposure as possible. The residual urine 
in the flask was boiled for nine minutes, and two additional ‘heated’ and 
covered glasses were charged with the boiled urine, and to one of these a drop 
of tap water was added. I shall speak of those again by and by. As regards 
those charged with the unboiled urine, one was exposed for forty minutes to 


280 ON THE GERM THEORY OF PUTREFACTION 


the air of the room ; one was exposed for nine and a half hours ; and the other 
two (those with the porcelain covers), were, in the first instance, not exposed at 
all. The one exposed for nine and a-half hours to the air, showed, in four days, 
besides some minute plants of filamentous fungi, opaque spots in the cloud of 
mucous deposit, and next day the liquid was turbid with perfectly character- 
istic and abundant bacteria, and had acquired a rank, strong odour. The urine 
exposed for forty minutes showed indeed no bacteria, nor any torulae or other 
organisms except three plants of filamentous fungi, which appeared to be of 
three different species, judging from their differences in density and rate of 
growth. They continued to grow until at last they almost filled the wine-glass, 
the fluid above them retaining its transparency unimpaired. When they had 
grown too large for their wine-glass, I transferred them to a large goblet into 
which urine had been passed, with the same sort of antiseptic precautions as were 
before described, after the goblet had been heated along with its saucer-like 
cover, and allowed to cool under a glass shade, packed round its base with cotton- 
wool to exclude dust. In this goblet the fungi continued to develop ; and one 
growing more rapidly than the rest at length overlapped and smothered them, 
and then continued to grow alone till, by the end of January, ten weeks after 
the commencement of the experiment, the goblet was almost full of the delicate 
white filamentous mass, which, with the bright unaltered amber-coloured liquid 
above, presented a very beautiful appearance. At length, in the early part of 
February, I observed that the whole urine had become turbid, and at the same 
time the fungus, which before had continued to grow steadily upwards, had 
suddenly collapsed into about a third of its former volume. On examination 
I found that the liquid had a strong smell, and contained multitudes of minute 
granules grouped irregularly in a different manner from that which prevails 
among bacteria. In bacteria, where more than two constituent elements are 
connected together, they are commonly arranged in a linear series, constituting 
what are termed leptothrix filaments, as seen in Plate VI, Fig. 3 6 and Fig. 4. 
3ut in the case of these granules, when three or four were associated, they never 
showed themselves in a line, and when only two were together the members 
of the pair were often dissimilar in size. Yet, though unlike bacteria, there 
could be little doubt that these granules were some species of organism, and 
the natural interpretation was that it had found its way into the glass, and, 
developing in the urine, had rendered it poisonous for the fungus, just as is 
commonly seen when bacteria grow along with Penicillium Glaucum in urine. 
The bacteria occasion putrefaction in the fluid, and when this has advanced to 
a certain degree the growth of the penicillium is arrested. 

[ had before met with granules of similar size and grouping. They occurred 


AND OTHER FERMENTATIVE CHANGES 281 


in one of the two glasses of boiled urine in this experiment. To one of those 
glasses, it may be remembered, a drop of tap water was added, while the other 
was simply covered with a glass plate. In the former glass bacteria of usual 
appearance showed themselves, as was to be expected; but it was five days 
before they occurred, whereas a specimen of the same urine unboiled presented 
bacteria in abundance in two days when similarly treated. This, I may remark, 
implied that the unboiled urine was a much more favourable nidus for the 
development of these organisms than the boiled liquid, and therefore a more 
sensitive medium to experiment with. The other glass of boiled urine, to 
which no water was added, continued unchanged for three weeks, which was 
more than could have been expected, as it was covered merely with a plate of 
glass, there being no room for it under the glass shade. But at the end of that 
time the urine became turbid, and I found under the microscope multitudes of 
granules, of which samples are represented at a in Plate VI, Fig. 5, resembling 
what I have described as occurring in the goblet. Plate VI, Fig. 5 5, represents 
another specimen of similar bodies which occurred in a glass of unboiled urine 
about the same period. I have introduced this sketch because it shows the 
peculiar irregular groups formed when several are together, as well as the variety 
of size of the individual granules. 

That these granules were really organisms I had once an unexpected oppor- 
tunity of proving. On the 5th of February, of the same year, I was examining 
some of them which had grown in a glass of unboiled urine, diluted with twice 
its bulk of distilled water which had been boiled and allowed to cool, and as I 
proceeded to sketch the group represented at c, in Plate VI, Fig. 5, I saw that 
it grew under my eyes. When I began the sketch, the lower three members of 
the group were a pair. About ten minutes later, at 9.4 a.m., the three had 
become four, as seen at c,, where also the constituents of the other group of 
four are seen to have increased in bulk. By 9.30 the lower four had grown to 
seven, as is shown at c,,1 where also the left-hand granule is seen to be greatly 
swollen. At 9.50 the upper four granules were observed to be each faintly 
marked by a transverse line, and finally by 10.36 those four had become deve- 
loped into eight, as shown at c,, while the large granule most to the left was 
marked by a cross, indicating that it was undergoing division into four. The 
‘fissiparous generation’ thus observed to take place was clear proof that these 
little bodies were really organisms ; while the manner in which the divisions 
occurred appeared to mark the species off from bacteria, in which the only 
recognised segmentation is in a line transverse to the longitudinal axis, as is 


1 There were, no doubt, in reality eight; one of them being obscured by lying beneath the 
quadruple granule just formed out of one of the single ones. 


282 ON THE GERM THEORY OF PUTREFACTION 


illustrated by the sketches given in Fig. 4 (see explanation of the Plates). This 
mode of growth explained also the peculiar arrangement of the granules, which 
serves to distinguish it from bacteria, viz. that when three or four are present 
in a group they are not, as a rule, arranged in a straight line. I suggest provi- 
sionally the name Granuligera for this little organism, of which there may, for 
aught I know, be various species. Its distinction from bacteria is a matter of 
considerable interest, because, although destitute of anything like vital move- 
ment, it often renders fluids as turbid as bacteria, and like them produces a 
rank smell in urine, followed in a few days by strong ammoniacal odour. So 
far as urine is concerned, therefore, it seems to be an instance of an organism 
different from bacteria giving rise to putrefaction. 

About this time my study suffered from an epidemic of granuligera. I could 
not now perform the same experiments with the same success as in the first 
instance: any that I tried was sure to be followed by the development of this 
pervading organism. I eluded it, however, by continuing the investigation in 
a room at the top of the house, which had been for a considerable time un- 
occupied. Here the results of experiments corresponded with those originally 
obtained in the study. 

But I have not yet spoken of the two glasses of the second experiment 
which were not exposed, but were kept covered with the evaporating dishes 
under a glass shade. The liquid in both these glasses having remained unaltered 
for nearly a fortnight (thirteen days), I exposed one of them to the air for nine 
hours in my study, which is a warm room (over the kitchen), the weather being 
dry and frosty, and then replaced it, covered as before, under the glass shade, 
having previously ascertained that the odour was that of perfectly fresh urine. 
Two days later the cloud of mucus presented a multitude of vertical white 
streaks, and the side of the glass was also similarly marked, and when another 
day had passed the whole liquid was manifestly turbid, and there were also 
two little patches of scum upon the surface. On microscopic examination I 
found that the scum was composed of a species of torula, and that the turbidity 
was due to a small organism which, while motionless like granuligera, resembled 
bacteria in its mode of segmentation and arrangement. It is represented in 
the sketches given at c in Plate VI, Fig. 3, where it will be observed that when 
three elements exist together they are in a straight line, and that some of those 
which are in pairs present a transverse line of incipient division through each 
constituent portion. Occasionally this organism was met with in the form of 
long chains (leptothrix), and it is plainly referable to the bacteric group. But 
no filamentous fungus occurred from first to last in this glass, which, in that 
respect, was the exact converse of the one which was exposed to the atmosphere 


AND OTHER FERMENTATIVE CHANGES 283 


in the first instance for forty minutes, and in which, it will be remembered, 
filamentous fungi occurred without either torulae or bacteria—the obvious 
explanation of the difference being that different organisms happened to prevail 
in the air of the rocm at the two periods of exposure. 

The other glass was left permanently covered; aiid the urine in it remained 
permanently free from organic development or putrefactive alteration. After 
the lapse of many weeks, when its bulk had been considerably reduced by 
evaporation, it became turbid, leading me to suspect bacteria. But on apply- 
ing the microscope I found the appearance was occasioned merely by saline 
deposit, and the contents finally dried up into a solid residue, without under- 
going any other perceptible change. 

I need hardly point out how entirely such a fact as this disposes of the 
oxygen theory as regards this particular fluid at ordinary temperatures. Neither 
cover nor shade fitted closely, so that a constant interchange was taking place 
by diffusion between the air in the wine-glass and the oxygen and other gases 
of the external atmosphere ; yet no putrefaction or other fermentative change 
occurred. Nor is the fact less significant in its bearing upon the theories of 
chemical ferments and spontaneous generation. The vesical mucus has been 
commonly regarded as the special chemical ferment of urine: but it was here 
present, unaltered by boiling or any other treatment, yet failing for weeks 
together to produce any fermentative change. And the mere fact that the liquid 
was received into a vessel which had been heated so as to destroy all life within 
it, and afterwards protected from the access of dust, ensured the absence from 
first to last of all organic development. It is, therefore, certain that this urine 
contained no materials or principles capable at ordinary temperatures of evolu- 
tion into living beings. 

At the same time the behaviour of the glasses which were exposed to the 
air in this experiment indicates that the foreign element which gives rise to 
bacteria, like that which occasions the growth of filamentous fungi and torulae, 
may enter in the form of atmospheric dust. 

But the results of this simple experiment were valuable in other respects. 
In the first place, it afforded ample proof that urine may be obtained pertectly 


1 It may be urged that the particles of dust which give rise alike to the development of organisms 
and to- fermentative changes in a fluid like urine are not necessarily organisms, but may possibly be 
little bits of so-called chemical ferments which occasion chemical alterations, that in their turn lead to 
the evolution of organisms by spontaneous generation. Such a view, plausible as it may appear, will 
be shown in the sequel to be utterly destitute of scientific basis. Meanwhile we must be content with 
the sure step mentioned in the text, viz. the fact that neither fresh healthy urine nor its mucus contains 
any such evolutionary particles. I feel justified in stating this as a general truth regarding urine, since 
it has been found to hold not only in numerous other experiments with this liquid derived from the 
same source, but also when it was obtained by the same method from two other individuals. 


284 ON THE GERM THEORY OF PUTREFACTION 


free from organisms by merely applying an efficient antiseptic as a preliminary 
measure to the meatus uvinarius ; and I have before referred to the high interest 
which attaches to this point. 

Secondly, it showed that if an organic liquid is obtained in an uncontami- 
nated state to begin with in a ‘ heated’ wine-glass, covered with a ‘ heated ’ 
cap shaped like an evaporating dish, and further protected by a glass shade, 
we are secure against the introduction of any organism from without, so long 
as the arrangement is left undisturbed. 

Further, the permanent freedom from contamination in this glass was 
particularly satisfactory, because, seven days after it was charged, I had re- 
moved a drachm of the liquid from it by means of a “ heated’ pipette, in order 
to ascertain the effect of water upon the unboiled urine as above alluded to 
(see p. 278). If no organic development resulted from the sudden entrance of 
so considerable a volume of air as then passed into the glass to take the place 
of the liquid withdrawn, it follows that, various as are the organisms which 
float in the atmosphere, they constitute but a very small proportion of the 
abounding particles of dust which a beam of sunlight reveals in an occupied 
apartment. 

A similar inference must be drawn from the circumstance before mentioned, 
that the sole result of forty minutes’ exposure of one of the glasses of this experi- 
ment to the air was the development of three plants of filamentous fungi, whereas 
the particles of dust which fell into it during that time must have been very 
much more numerous. 

If, then, the withdrawal of a drachm of liquid, or exposure for more than 
half an hour had so little effect, it was plain that the removal of one or two 
minims, executed nimbly so as to involve little more than momentary exposure, 
must be practicully free from the risk of accidental contamination. 

I thus became possessed of a means of making observations upon these 
minute but highly important organisms, which promised to yield results of a 
more definite character than any which had been hitherto obtained. 

Various detailed accounts have been given of late years, not only of the 
spontaneous generation of animal and vegetable forms of more or less com- 
plexity, such as large ciliated infusoria from an infusion of hay, or torulae and 
penicillia from milk globules, but also of the transition of one form of organism 
into another. But in the latter class, as in the former, the liability to deception 
is so extremely great, in consequence of microscopic organisms accidentally 
present developing side by side with the minute objects investigated, and pre- 
senting the appearance of growing out of them, that, without the slightest 
doubt being thrown upon the good faith of the observers, the so-called facts are 


: 
: 
j 
4 
: 
‘ 
4 


AND OTHER FERMENTATIVE CHANGES 285 


justly received with the gravest suspicion. But with the means now at our 
disposal the grand source of error in former similar inquiries might be eliminated, 
and results of a more satisfactory character might therefore be anticipated. 
I was thus led to prosecute the investigation far beyond what I had at first 
intended, and will now proceed to give a selection from the results. 

That which I will mention first has reference to the origin both of torulae 
and of bacteria. 

On the evening of the 13th of December, 1871, during a drizzling rain which 
had been falling all afternoon, I took a ‘heated’ wine-glass with its cover out into 
the street, and, raising the cover, allowed a few drops of rain to fall into the 
glass, and having covered it again and brought it back into the house, I charged 
it with unboiled urine from a ‘heated’ flask, the arrangements for obtaining 
the liquid being the same that have been before described. In the course of two 
days I noticed a tiny opaque streak proceeding vertically downwards from 
a point on the inside of the glass; and on the following day the streak had 
increased, and the cloud of mucus was speckled with numerous white points. 
On the fourth day, while the speckling of the cloud had increased, and the 
streak had become coarsely granular, two little plants of filamentous fungi were 
also seen floating in the clear liquid. By the fifth day the specks in the mucous 
deposit had assumed the appearance of coarse grains of white sand, and similar 
granules were sprinkled over the lower part of the inside of the glass. I removed 
one of these granules with ‘heated’ pipette, and examined it microscopically. 
It proved to be a very beautiful torula, composed of pullulating oval cells of 
great delicacy, disposed in groups, of which one is represented in Plate VI, 
Fig. 6a. Though not very different in size from the yeast plant, it proved 
itself to be a totally distinct species, not only by the more delicate and less 
granular character of the cells, but by the fact that it grew thus luxuriantly in 
non-saccharine urine, in which the Torula Cerevisiae will only grow with extreme 
difficulty. For the sake of distinction I may term it Torula Ovalis, on account 
of the oval form of its cells. When ten days had elapsed after the mingling 
of the rain water with the urine, the white granular deposit had greatly increased, 
and some scum was also present on the surface, which the microscope showed 
to consist of the same oval torula. But the two plants of filamentous fungi had 
subsided and had apparently ceased to grow; the liquid, though still brilliantly 
clear and but very slightly affected in odour, having doubtless become unfit 
for their development through chemical changes induced by the torula. Another 
small fungus plant, observed several days before upon the side of the glass 
below the level of the lhquid, seemed, however, to be still increasing. At this 
time having occasion to go into England for a few days, and being desirous 


286 ON THE GERM THEORY OF PUTREFACTION 


of continuing the investigation, I took some of the liquid with me, decanting 
a drachm of it with ‘ heated’ pipette into a ‘ heated’ test-tube about five inches 
long, which I covered with an inverted test-tube of about the same length (of 
course also ‘ heated’), and packed the tube vertically in a box with cotton-wool. 
Five days later (on the 28th of December), having prepared some Pasteur’s solu- 
tion in a manner which I hoped would ensure absence of living organisms at the 
outset,! I inoculated about an ounce with half a minim of the urine in the test- 
tube, including some of the white deposit at the bottom. The glass, which was 
of course ‘ heated’, as well as its porcelain cap, was placed under a glass shade 
in a room varying in temperature from about 60° to 70° Fahr. It is necessary 
to state, that before raising the inverted test-tube which covered that containing 
the urine, I carefully wiped the mouth of the former with a rag dipped in a strong 
watery solution of carbolic acid; without this precaution there would have 
been a risk of contamination of the urine-tube with some portion of cotton 
or dust adhering to the covering tube.? The urine still continued quite bright, 
and on examining with the microscope the residue in the pipette after the in- 
oculation, I found it to consist of the oval torula unmixed with anything else. 
Thirty-six hours after the inoculation I found the inside of the glass that 
contained the Pasteur’s solution sprinkled over from top to bottom with a fine 
granular deposit resembling white sand under a pocket-lens, and about a third 
of the surface of the liquid was occupied by a dense white scum which micro- 
scopic examination on the following day showed to consist of oval torula cells, 


* In preparing the liquid I deviated to some extent from Pasteur’s formula, which is 100 parts 
distilled water, 10 parts pure sugar-candy, 1 part tartrate of ammonia, and the ashes of 1 part of yeast. 
I employed lump-sugar instead of sugar-candy, and reduced its proportion by one half, as it seemed to 
me likely to prove somewhat too strong to suit some organisms. Further, as I had not at hand a refer- 
ence to enable me to ascertain how much of the mineral salts Pasteur employed, I used what seemed 
to me about a suitable amount for a fungus to consume, judging from the quantity that I got by in- 
cinerating a certain weight of yeast ; and this, as I afterwards found, was a little more than Pasteur’s 
proportion. My solution, then, had the following composition :— 


Distilled Water. : : : 1 ESOOOISES: 
Lump-Sugar , : : 250 gers. 
Crystallized Tartrate of Ammonia : 50 grs. 


Dry Ash of Yeast ; : : : 5 grs. 
making rather more than half a pint. The liquid was introduced through a ‘ heated’ funnel into a 
‘heated’ Florence flask provided with a ‘ heated’ glass cap, and was boiled and allowed to cool in the 
pure and covered vessel. A better method of procedure will be described in a later part of this com- 
munication. 

* The efficacy of a strong watery solution of carbolic acid for the destruction of minute organisms 
was familiar to me from experience in antiseptic surgery ; and it is also well illustrated by the method 
of obtaining uncontaminated unboiled urine described in the text. The fact is of great value in experi- 
ments on this subject, as it affords a simple and sure mode of purifying portions of apparatus which it 
would be inconvenient or impossible to subject to heat. And the extensive experience which this 
investigation has involved, enables me to state with confidence that wiping a piece of glass with a rag 
moistened with a solution of carbolic acid in twenty parts of water as efficiently destroys adhering 
organisms as heating to redness in a flame. 


ee eeeE EEE 


a 


| 
| 


AND OTHER FERMENTATIVE CHANGES 287 


closely resembling those in the urine of inoculation. A group of these from the 
Pasteur’s solution is represented at a, Plate VII. On the 3rd of January, 1872, 
I inoculated a second ‘ heated’ and covered glass of the same stock of Pasteur’s 
solution by introducing into it a drop from the former glass of the same fluid 
containing the growing organism, and in the course of the next twenty-four 
hours the cells of Toru/a Ovalis were again seen under the microscope in a deposit 
on the side of the glass. Next day, being about to return to Edinburgh, I intro- 
duced some of the contents of this second glass of Pasteur’s solution into a 
‘heated’ test-tube provided with an inverted test-tube cover, and packed the 
tube with cotton-wool in a box along with that containing the urine. Mean- 
while, although eleven days had elapsed since the urine was decanted into the 
test-tube for the journey south, the liquid remained perfectly transparent, and 
showed no appearance of any other organism besides the Torula Ovalis ; so that 
it may be assumed that the plants of filamentous fungi present in the original 
urine-glass had been avoided in the process of decanting, and that the Torula 
Ovalis existed in the test-tube unmixed with any other organism. 

Being occupied with other matters, I did not look at these test-tubes again 
until seven months had passed, during which time they had remained undis- 
turbed in the cotton-wool in which they were packed. This proved to have 
been a very fortunate arrangement, the long narrow form of the vessels and 
their covers, and the mass of cotton about them, having so interfered with 
evaporation, that a considerable proportion of the liquid remained in the glasses. 
On closely inspecting them on the 6th of August, 1872, I saw that in both the part 
of the glass that had been left dry by the slow evaporation was studded over with 
little round whitish gelatinous-looking bodies, smaller than pins’ heads, which 
I thought might perhaps be a fungus related to the torula, a surmise which 
was at once verified by examination of the glass containing the urine. Having 
raised the test-tube cover, after wiping its lower part with 1 to 20 watery solu- 
tion of carbolic acid, I succeeded in picking up with a mounted needle (passed 
through the flame after washing the wooden handle with carbolic solution), a 
portion of one of the little gelatinous bodies, and submitted it to the microscope. 
It proved to be made up of plants of an exquisitely delicate filamentous fungus, 
of which 6, in Plate VI, Fig. 6, represents one young plant entire, giving off 
a branch, and c a somewhat larger plant, bearing two oval bodies considerably 
thicker than the thread from which they spring, which must be looked upon as 
spores (conidia). In d, e, and f/ are given portions of other filaments bearing 
similar conidia. Such conidia were also seen free and pullulating, either in pairs, 
as in g, #, and 2, or more rarely in somewhat larger groups as at k, which, in 
fact, constituted a torula undistinguishable from the original Torula Ovalls. 


288 ON THE GERM THEORY OF PUTREFACTION 


But while some of the buds proceeding from the filaments had thus the char- 
acter of toruloid conidia, differing from ordinary branches not only by their 
form but by their thicker and more substantial character, it was more common 
to see sprouts presenting the opposite condition of extreme slenderness, as at 1 
and o, and similar delicate bodies were often seen free, commonly in pairs, as 
represented in the series /, £, g, y. Of these, / resembles in its thicker half a 
very young plant such as m, while its more slender portion corresponds with /. 
This again, as well as the still more delicate g and 7, seemed to be neither more 
nor less than bacteria, as was shown not only by their form, but by the fact 
that precisely similar bodies were not unfrequently seen exhibiting active and 
perfectly characteristic movements. Further, there were many motionless 
bodies, such as s, which previous experience enabled me to recognise as young 
bacteria multiplying by segmentation, while they were fully equal in thickness 
to sprouts, such as 0, proceeding from the filaments. The identity of the bacteria 
with the filaments was further indicated by the precise similarity of the delicate 
transverse markings often observed in the former (as in # and 7) with those of 
young plants, such as m. 

That bacteria should originate from filamentous fungi was an idea entirely 
opposed to the preconceived notions with which I entered upon this inquiry ; 
for, in common with those authorities on the subject whose observations ap- 
peared entitled to greatest weight, I had regarded these organisms as a separate 
and altogether distinct group. But the contrary conclusion was forced upon 
me not only by the observation which I am now recording, but by various 
others, some of which will be described in the sequel. I need hardly remark 
that, if correct, it is of the very highest interest. 

In the present instance it is certain that the bacteria moving in the liquid 
were identical, morphologically, with buds derived from the fungus ; and this 
fact receives additional weight from the circumstance that the glass had been 
left untouched for seven months, having been previously securely guarded 
against the entrance of organisms from without ; and even if bacteria, as such, 
had been accidentally introduced when the vessel was last exposed, it is in the 
highest degree improbable that they would have remained in an active condition 
for such a protracted period. If, therefore, we set aside the idea of spontaneous 
generation, which I trust before this paper is concluded the reader will see 
that we are justified in doing, it is difficult to conceive how these bacteria could 
have arisen, except from a gradual alteration in the character of the original 
organism under the influence of progressive changes in the medium which it 
inhabited.? 


* It is indeed conceivable that a bacterium incapable of growing in fresh urine may have lain 


AND OTHER FERMENTATIVE CHANGES 289 


I next proceeded to examine the Pasteur’s solution. The liquid was still 
perfectly transparent and colourless, contrasting remarkably with the jet-black 
colour which I had observed to result in a much shorter period from the action 
of yeast upon the same fluid.1. There was, however, a good deal of white deposit, 
partly in the form of a loose sediment, partly as a delicate incrustation upon 
the side of the tube, and some white patches were floating free, probably in 
consequence of the disturbance of the vessel: there was also a little scum on 
the surface. Only about a sixth part of the liquid had evaporated ; and, as 
before mentioned, the part of the glass which had been left dry was studded 
over with little gelatinous bodies like those in the tube of urine. The tube 
being longer in the present case, I failed to pick out any of those little bodies 
with a needle. I was therefore obliged to content myself with examining a 
drop taken with ‘ heated’ pipette from the upper part of the liquid, including 
some of the white floating particles. These, however, proved all that I could 
desire, being composed of the same organism that I had found in the urine, and 
all the better seen because it had not been disturbed by the needle. 6, c, and d 
of Plate VII represent three entire plants, of which 0) fully equals in slenderness 
any seen in the urine; and some idea of its exquisite delicacy may be given 
by saying that ten such threads might le abreast in the diameter of a single red 
corpuscle of human blood. d is introduced as a good example of the production 
by such filamentous plants of substantial conidia having the characters of the 
cells of Torula Ovalis, while in c we have a plant which in some parts is as delicate 
as 6, while in others it looks as if composed of elongated cells of the torula. 
Other obviously transitional forms between the filamentous fungus and the 
torula are represented by the groups e, /, and g. Comparing the appearances 
of the organism as it occurred in the two glasses, the cellular element predomi- 
nated over the filamentous in the Pasteur’s solution, while the converse was the 
case in the urine. The toruloid groups, rare in the latter liquid, were abundant 
in the former, in which also the filamentous plants were as a rule of a coarser 
character, and were invariably small; that is to say, not extending to any 
great length, as they did in the other medium. The granules of the filaments 
and the nuclei of the cells were also much more marked in the Pasteur’s solu- 
tion. Along with this deficiency of the filamentous element, the bacteric form 
was absent in the Pasteur’s solution. Some of the buds were indeed as slender 


dormant in the liquid till it had become so altered under the influence of the torula as to be a suitable 
nidus for it. Meanwhile the fact of the morphological identity of this bacterium with buds from the 
filamentous fungus must be taken for what it is worth. 

* IT am not prepared to say whether the black colour which I have invariably found to be caused 
by the prolonged action of yeast upon Pasteur’s solution is due to the Tovula Cerevisiae or to other 
organisms accompanying it. 

LISTER I U 


290 ON THE GERM THEORY OF PUTREFACTION 


as the bacteria of the urine, as is illustrated by the plants 6 and c, and here and 
there such buds were seen floating free in pairs such as /, but no bacteric move- 
ment was to be seen. This puzzled me at the time; but I afterwards found 
that it was no reason for surprise, and I shall hereafter have occasion to mention 
cases of bacteria of ordinary form and active movement in urine, assuming 
a motionless character and at the same time a very different appearance in 
other media. 

Although the proof already afforded of the identity of the Torula Ovalis 
with the filamentous fungus may appear sufficiently ample, yet, as the point is 
of extreme interest, I have been well pleased to obtain further confirmation of the 
fact while preparing this communication for the press. On the 9th of November, 
1873, I once more removed the test-tube containing the Pasteur’s solution from 
its cotton packing to see what change it might have undergone. I found about 
half of the original volume of the liquid still remaining unevaporated. It was 
still transparent, but it was now of a pale brownish-yellow colour, and the sedi- 
ment had a similar tint. A delicate incrustation existed on the interior of the 
glass, but did not reach up to the level of the liquid, and the gelatinous lumps 
had disappeared from the dried part above. Raising the test-tube cover with 
careful antiseptic precautions, I removed a few drops, taking up at the same 
time a little of the crust, which I detached from the side with the ‘ heated’ 
pipette ; and, after inoculating a glass of Pasteur’s solution with about half 
a minim, I proceeded to investigate the remainder. Under the microscope the 
solid constituent proved to be composed in the main of granular masses, looking 
like confused aggregations of the organism in an effete and degenerate state ; 
but projecting from the edges of these masses were plants and corpuscles, which, 
from their translucent and fresh appearance, made me hope that they were 
alive. The filaments closely resembled those seen in this glass a year and 
a quarter before, except that they were invariably very short, and the corpuscles, 
while sometimes in groups more or less resembling the original torula, were 
often of a more elongated form and strongly nucleated. During the first five 
days after the inoculation there was no distinct appearance to the naked eye 
of any growth taking place in the new glass of Pasteur’s solution. At the end 
of that time, however, thinking that a speck of delicate scum, which existed 
from the first, appeared slightly increased, I examined a portion microscopically, 
and found it to consist entirely of cells which appeared of new formation, some 
of them presenting transitional forms between the elongated bodies common 
in the test-tube and the constituents of the oval torula. The growth after- 
wards continued, both as a very delicate scum, and as a fine white deposit ; 
but its rate was extremely slow, and the product for the most part on a much 


~ 


AND OTHER FERMENTATIVE CHANGES 201 


smaller scale than the original torula, and more resembling the elements found 
in the test-tube. 

Very different was the behaviour of the organism in unaltered urine. Two 
days after the inoculation of the Pasteur’s solution, I introduced half a minim 
of the liquid from the test-tube into a ‘ heated’ and covered glass, containing 
unboiled urine from a flask which had been charged on the first of March, but, 
though it had furnished the material for many successive experiments, retained 
its original characters unimpaired.’ For two days there was no appearance of 
growth ; but on the third day a small patch of scum, which had been the im- 
mediate result of the inoculation, was considerably increased in size, and had 
acquired a much coarser character, and several small detached specks of similar 
aspect were floating on the surface. The side of the glass was also sprinkled 
with minute particles like grains of white sand, often disposed in vertical streaks, 
while other similar granules were deposited at the bottom, the liquid retaining 
its briliant clearness. In short, the naked-eye appearances were an almost 
exact reproduction of those which resulted from the introduction of the rain 
drops into the original urine nearly two years before, and on applying the 
microscope to a portion of the scum taken up with ‘ heated’ pipette, I was 
delighted to find 1t composed exclusively of the Torula Ovalis in all its original 
beauty, the constituents cells pullulating freely, as shown at 7, Plate VII, which 
represents, for convenience of sketching, a small specimen of the groups, which 
were commonly much larger, like those of the yeast plant when in full activity. 
In some fields the cells were peculiarly large, as at m, and here and there, as at 
Zand n, a cell was somewhat longer than usual, just as occurs in Torula Cere- 
vistae ; but there was no appearance of filamentous growth. It was a torula 
pure and unmixed ; yet its identity with the Torula Ovalis and its distinction 
from the yeast plant were declared not only by the form and aspect of the cells, 
but still more by the fact that, just like the original specimen, it grew freely 
in non-saccharine urine, in which Torula Cerevisiae develops only with extreme 
difficulty. uy 

The organism, having thus, after many months of slow growth in the fila- 
mentous form in the altered Pasteur’s solution, recovered its purely toruloid 
and luxuriant habit in the medium in which it presented those characters at the 
outset, retained them when transferred to uncontaminated Pasteur’s solution. 
For having, with the touch of a ‘heated’ pipette, introduced a speck of the 
rapidly growing scum from the urine into a second glass of Pasteur’s solution, 
which had been charged along with the former six days before, but had hitherto 

’ The method by which this flask was prepared, and the mode of decanting into the experimental 


glasses, will be described in a later part of this paper. 
U2 


292 ON THE GERM THEORY OF PUTREFACTION 


remained unchanged, I found the morsel of scum increased in fourteen hours to 
four times its original diameter, and on the following day it nearly covered the 
surface of the liquid, and the side of the glass was sprinkled with white granular 
specks, which after another day were disposed in vertical streaks, just as they 
had been in a glass of Pasteur’s solution inoculated from the original urine- 
glass nearly two years previously. And on examining the scum microscopically, 
I found it to consist of the torula unmixed with any filamentous element, as 
seen in 0, ~, g, 7, and s, Plate VII. 

Those who have the patience to follow me through these minute details, 
inseparable from so minute a subject, will acknowledge the importance of having 
it clearly demonstrated that an organism, which, for weeks together and in 
different media, showed itself as an unmixed torula, was in reality a conidial 
development from a filamentous fungus. Forone such instance rigorously proved, 
leads to the suspicion that the same is in all probability the case with the whole 
group of torulae, and that though Berkeley appears to have been deceived 
when he thought he traced a direct connexion between Torula Cerevisiae and 
Penicillium Glaucum,' yet his belief that the yeast plant is derived from some 
filamentous form will turn out to have been sound when the mode of investiga- 
tion which I have been describing shall have been applied to that case. Without 
some such method, permitting us to study an organism for a protracted period, 
unmixed with others, in different media or in the same medium altered under 
its fermenting influence, the true affinities of the Torula Ovalis would have 
remained as obscure as those of Torula Cerevisiae are at present. Further, 
without entering here upon all the bearings of this observation, it may be 
remarked that for an organism so humble as a torula, though modified by vary- 
ing circumstances, to retain its specific morphological and physiological characters 
unimpaired for two years together, is a fact fraught with the deepest instruction. 

I next unpacked and examined the test-tube containing the urine. I found 
the fluid all evaporated except about two minims above a considerable crystal- 
line mass. The part of the glass, about an inch high, left exposed by the drying 
was studded over as before with round gelatinous specks, those on the upper 
half-inch being largest, viz. about 1-50th inch in diameter. Breaking the tube 
with antiseptic precautions, I examined one of the little transparent lumps 
with the microscope, and found it to consist almost exclusively of the filamentous 
form of the fungus, the conidial element being, as before, much less marked 
in this tube than in that of Pasteur’s solution. There was a somewhat larger 
proportion of conidia in the liquid residue, which, however, was thick from the 
abundance of the fungus filaments in it; but there was no longer any appear- 

* See de Bary, Morphologie und Physiologie dey Pilze, &c., Leipzig, 1866, p. 184. 


AND OTHER FERMENTATIVE CHANGES 293 


ance of bacteria. I introduced a portion of the gelatinous lump into a glass of 
uncontaminated urine, which had been charged along with the one inoculated 
from the tube of Pasteur’s solution (viz. nine days previously) ; but as no growth 
showed itself in the course of the next eleven days, I concluded that the 
organism had, in the highly concentrated and altered urine, at length lost its 
vitality. Yet the examination of this urine-tube proved not devoid of interest. 
For although the bacteria which were seen in it when it was last examined had 
the ordinary rod shape, and did not differ in appearance from those commonly 
seen in putrefying urine, yet the liquid in this glass had no ammoniacal odour, 
but a very peculiar smell resembling musty cheese rather than urine, and it 
was sharply acid to test-paper, even when diluted with several times its bulk 
of water. Here, then, we have an example of what we shall see abundantly 
illustrated in the sequel, viz. that bacteria of similar morphological characters 
may differ entirely as regards the fermentative changes to which they give rise, 
being, like the torulae, as specifically distinct as the fungi from which some of 
them at least appear to take their origin. 

The observations to which I have next to direct attention were made upon 
a filamentous fungus, which I was induced to investigate in the hope that it 
might prove to be the parent of the Torula Cerevisiae, occurring as it did in 
circumstances analogous to those under which the filamentous form of the Torula 
Ovalis had been met with. I had introduced into a ‘ heated’ and covered glass 
of Pasteur’s solution a morsel of German yeast, with the effect of inducing the 
usual evolution of gas that accompanies the alcoholic fermentation, followed by 
the gradual supervention of the black colour before alluded to. Some minute 
plants of filamentous fungi, seen in the course of the first few days, had appa- 
rently ceased to grow, and no penicillium or other ordinary fungus appeared ; 
but after the lapse of two months I observed, upon the surface of the liquid and 
upon the part of the glass left exposed by evaporation, a low white mould, 
which, under the microscope, was seen to be composed of branching septate 
filaments and fructifying threads, the latter in somewhat irregular forms, but 
most frequently producing moniliform terminal chains of spores; the fungus, 
though apparently too insignificant to have attracted the notice of mycologists, 
being referable to the genus oidium. The largest of the spores were not unlike 
those of yeast; and other similar spores were seen in toruloid groups in the 
scum that existed on the surface of the liquid. Hoping that I had discovered 
the filamentous form of the Torula Cerevisiae, I was anxious to investigate this 
mould further; but having used all the scanty growth for the examination 
already made, I set the glass aside to allow further development, and circum- 
stances prevented me from looking at it again till nearly four months more had 


294 ON THE GERM THEORY OF PUTREFACTION 


elapsed. I then found the sour liquid blacker than ever, and further reduced 
by evaporation, the only other change visible to the naked eye being that the 
same low white mould had grown again in small amount upon the side of the 
glass. Finding that it still retained the same characters under the microscope, 
I hoped that by transferring it to a saccharine solution I might get it to repro- 
duce the Torula Cerevisiae, just as I had got back the Torula Ovalis by placing 
its filamentous form in fresh urine. Accordingly, having taken up a portion of 
the mould with a ‘ heated’ knife, I introduced a morsel of it into a ‘ heated’ 
and covered glass containing freshly prepared Pasteur’s solution, and placing 
the remainder in a drop of water between plates of glass, made a further examina- 
tion with the microscope. a, in Plate VIII represents a fructifying filament, 
the segments of which are some of them in the form of a moniliform chain of 
spores, while others present a transverse line indicating tomiparous division 
into gemmae, and one has given off a conidial bud, the last being an appearance 
comparatively rarely seen in this fungus when first removed from the wine- 
glass. But on examining again, after fifteen hours, the same specimen, which 
had been kept in a moist atmosphere to prevent evaporation, I found free spores 
in considerable numbers about the filament previously sketched, and the fila- 
ment itself was studded with numerous fresh conidial buds, as shown in outline 
at a,, the one previously present having dropped off. The great rapidity with 
which this conidial budding took place under the influence of the water is further 
indicated by the sketch at a, taken only two hours later, where all the buds 
present at the former examination are seen to have either grown larger or to 
have dropped off, while several fresh ones have made their appearance. 

This abundant formation of conidia in the new medium increased my hopes 
that I should get back the Torula Cerevisiae in a saccharine fluid. This hope, 
however, was doomed to disappointment. So far from the organism exhibiting 
in the glass of Pasteur’s solution a toruloid development, it assumed there the 
opposite condition of a filamentous growth, in which any appearance of conidial 
formation was a rare occurrence. 0, c, and d in Plate VIII represent sprouting 
conidia, ¢ a very young plant, and / the extremity of a filament. The entire 
distinction of this fungus from the yeast plant was further shown physiologically 
by the fact that it grew extremely slowly in the saccharine liquid, and failed 
to cause any evolution of gas in it, though kept under observation more than 
two months. I was thus led to conclude that this oidium had been merely an 
accidental concomitant of the yeast plant, having sprung, perhaps, from one 
of the adventitious filamentous plants noticed during the first few days in the 
glass, and having survived the chemical changes in the fermenting liquid under 
which the yeast plant itself had succumbed. 


AND OTHER FERMENTATIVE CHANGES 295 


But though disappointed of the results which I had hoped to have obtained 
from this oidium, I made some other observations upon it which proved to be of 
considerable interest. The remarkable conidial development which took place 
from it in water seemed such a striking instance of change of habit in the plant 
induced by a new medium, that I thought it worth while to try what effect 
would be produced upon it by various other liquids, and among the rest by 
unboiled and uncontaminated urine ; and on the 2i1st of August, 1872, I intro- 
duced into one of a series of ‘heated’ and covered glasses of that fluid, prepared on 
the roth of the month, and as yet unaltered, a minute portion of the organism 
from the glass of fresh Pasteur’s solution, where, as before mentioned, it was 
growing slowly in a filamentous condition; the delicate threads becoming 
broken up in the process, and diffused in an invisible form in the liquid. At 
the same time, for the sake of comparison, I inoculated from the same source 
another glass of Pasteur’s solution, as well as other lquids to which I need 
not here allude. In the fresh glass of Pasteur’s solution the growth proceeded, 
as in the previous one, in the form of branched and septate filaments, one of 
which is represented in outline at g, Plate VIII, on a smaller scale than the 
rest of the plate, while g’ gives in detail a portion of the same filament as seen 
under the usual higher power: and in the course of two days the naked eye 
detected white specks upon the side of the glass, which the pocket-lens showed as 
little woolly tufts. Meanwhile, in the urine the glass had also become sprinkled 
with white specks, but under the pocket-magnifier, while some of them were 
filamentous, as in the Pasteur’s solution, many presented a granular appearance. 

In examining the growth microscopically, I availed myself of an arrange- 
ment which I have often found advantageous. At the time of inoculation I had 
introduced into the urine a small plate of glass, with pieces of fine silver wire 
connected with its ends in the form of hooks, by which it could be suspended 
from the rim of the glass; so that, lying horizontally in the liquid, it might 
arrest as they fell organisms diffused through it. The little apparatus had of 
course been previously purified by heat. Such a plate being carefully removed 
with ‘heated’ forceps after development has advanced to any desired degree, 
and covered with a slip of thin glass, permits the examination of any growth 
that may have formed upon it, in a comparatively undisturbed condition. 
Thus, in the present instance, I was enabled to see im situ with the microscope 
the plants which the pocket magnifier had revealed. Under a low power they 
presented appearances such as are shown at a, b, and c, Plate IX, a being a 
purely filamentous growth, c a granular group, and 0 one exhibiting both char- 
acters in combination. Under the high power the granular parts were found to 
be composed either of groups of free pullulating cells of oval form, generally 


296 ON THE GERM THEORY OF PUTREFACTION 


disposed in pairs, as shown at e, Plate IX, or of plants of a most imperfect 
description, consisting of cells of a similar character to the free ones, or slightly 
more elongated, connected end to end, and often producing conidial buds, as in 
the specimen figured at d in the same plate. 

On the following day the difference between the two glasses was still more 
marked. The filamentous plants in the Pasteur’s solution had considerably 
increased, but those in the urine had almost all fallen to the bottom, their places 
being taken by abundant specks and streaks of granular aspect, and even the 
few plants that still remained adhering had lost their purely filamentous char- 
acter and had become granular. There were also little patches of scum upon 
the urine, whereas the surface of the Pasteur’s solution presented only some 
floating filamentous plants. I removed a portion of the scum with ‘heated’ 
pipette, and submitted it to the microscope, and found it to consist exclusively 
of free oval cells, like those seen in the granular specks the day before, as shown 
in outline at f. In the course of the next twenty-four hours all appearance of 
filamentous growth disappeared from the urine; but while the liquid, which 
was now for the first time observed to have a slightly offensive smell, had become 
unsuited for that mode of development of the organism, it had stimulated the 
corpuscular form in a most remarkable manner, the scum having increased 
with amazing rapidity. Thus, between 8 p.m. on the 24th and 5.30 a.m. on the 
25th, it grew from a loose patch, about half an inch in diameter, to a dense film 
that covered almost the entire surface of the liquid in the urine-glass, and eight 
hours later, the cell growth had been so great that the scum had become pushed 
up upon the glass to about a quarter of an inch above the level of the liquid, 
while the urine was rendered cloudy by the subsidence of detached cells. In 
the course of the afternoon the liquid had become turbid throughout, and the air 
in the glass shade was still more decidedly offensive ; yet, under the microscope, 
the only organism discoverable was that represented by the pairs of cells before 
described, so that we have here another clear example of fermentative change 
of putrefactive character induced in urine by other agency than bacteria. 
Samples of the cells are given in g, Plate IX, where they are seen to resemble 
those of d and e in having vacuoles, but no nuclei, merely, in some cases, incon- 
spicuous granules. In g is also given in outline a portion of the scum, showing 
how densely packed the constituent cells were, corresponding with the remark- 
able naked-eye appearance, which was that of a dense white layer, like a film 
of paraffin. 

On the same day (August 25), I introduced a small portion of this scum 
into a second glass of urine, prepared along with the former one fifteen days 
previously, but as yet retaining its brilliant clearness, and in other respects also 


AND OTHER FERMENTATIVE CHANGES 207 


unaltered, the transference being effected by a touch with the tip of a slender 
glass rod previously ‘heated’. The results of this inoculation differed from 
those seen in the former glass of urine in this, that no filamentous plants at 
all now made their appearance, while, on the other hand, the corpuscular mode 
of development proceeded with great rapidity. Thus, eight hours after the 
inoculation, the side of the glass already presented streaks having a granular 
aspect under a pocket-lens, and a portion of scum which had remained at the 
surface had increased to four times its original extent, presenting the same 
dense white character as in the former glass, like a film of wax or paraffin. I 
examined a portion of the scum microscopically, and found it to consist in the 
main of cells, free or in pairs, formed by pullulation, as shown (for the most 
part in outline) in the sketch given at 7, Plate IX. But there was besides 
frequently seen an appearance of somewhat longer sprouts, like an abortive 
attempt at the formation of filamentous plants, of which also specimens are 
given in the sketch 7. Twelve hours later the inside of the glass looked as if 
sprinkled over with coarse white sand, while the scum had grown so rapidly as 
to be more than eight times as large as when last observed. A portion of scum 
is represented in outline at k, where it is seen that there is no longer any appear- 
ance of long sprouts, the filamentous tendency having entirely disappeared, 
while the constituent cells are of smaller dimensions than before. Another 
point of much interest was the fact, that now, within twenty-four hours of the 
inoculation, the liquid, which, when inoculated, had the odour of perfectly fresh 
urine, was already markedly offensive ; and after the lapse of twenty-four hours, 
while the scum had almost covered the surface of the liquid, the rank smell was 
strong. Now it may be remembered that in the former glass no offensive smell 
was observed during the first three days, though the filamentous growth had 
proceeded luxuriantly, and that it was only after four days, when the filamentous 
form had given place to the corpuscular and the scum had made its appear- 
ance, that the rank odour was perceived. Hence we are led to infer that the 
same organism may differ in its effects as a fermentative agent according to its 
habit, the toruloid form in the present instance being a much more energetic 
ferment than the filamentous. I had the opportunity of verifying this observa- 
tion seventeen days later, when another glass of urine being inoculated with the 
same scum, there was again a rank smell in twenty-four hours. 

But to return to the glass under consideration. On the 27th of August, two 
daysafter inoculation, it stank as stronglyas the first glass; and now on examining 
a portion of the scum with the microscope, I was surprised to find a very remark- 
able change in its constituent cells, which, instead of being oval bodies with 
mere vacuoles and inconspicuous granules, and either free or in pairs, were 


298 ON THE GERM THEORY OF PUTREFACTION 


now of spherical form destitute of vacuoles, but strongly nucleated, as shown 
at /, Plate IX, and disposed in considerable irregular groups, as seen in the 
outline portions of the sketch. The same character was maintained by the scum 
in this glass during the rest of the time (fifteen days) that it was kept under 
observation, m being a sketch of its appearance after the lapse of ten days ; so 
that the organism had assumed completely the appearance of a spherical torula. 

But it may be asked, Was I not deceived in supposing that the new toruloid 
form in the second inoculated glass had anything to do with the oidium? May 
it not have been a totally different species accidentally present, just as the oidium 
itself was apparently adventitious in the yeast-glass ? That all the oval cells 
should have disappeared within twenty-four hours, and given place to another 
species producing a scum of the same remarkable naked-eye appearance, seemed 
indeed very improbable ; but, on the other hand, the difference of character in 
the cells was so remarkable, that if it was really only due to a modification of 
the same organism, it was desirable, if possible, to place the fact beyond doubt. 
With this object, on the 30th of August, I mingled a morsel of the scum, by means 
of a ‘ heated’ glass rod, with a drop of Pasteur’s solution! on a ‘heated’ slip of 
glass, and placed upon it a “ heated’ piece of thin covering glass, and over this 
a larger plate of thin glass also ‘heated’, overlapping the former one well on 
all sides, and luted down the margins of the upper glass with melted paraffin, 
applied with a hot steel pen. The object of this arrangement was that, while 
evaporation should be prevented by the paraffin luting, the interval between 
the thin glass plates might contain a supply of air to permit the growth of the 
fungus. I then selected for observation a group of the spherical cells near the 
edge of the liquid, and therefore near the air between the plates, and sketched 
them with camera lucida, as shown at 1,, Plate IX. This was at 5.50 p.m. 
At 6.8 p.m., I noticed a change in the nuclei of the cells, such as I have often 
observed in spores preliminary to germination, as indicated at 7,, and by II p.m., 
the object being still undisturbed under the microscope, the lowest of the cells 
had not only increased in size, but had produced a considerable elongated sprout 
(see ,), while the other cells were all markedly changed in the character of their 
nuclei. At midnight the sprout from the lowest cell had itself produced another 
sprout, also of oval form (see 1,), and by 7.45 next morning, when I next looked 
at the object, two other cells had been produced from the last sprout, while 
some, if not all the other cells of the group, had also germinated, giving rise to the 
appearance shown at m;. And it will be observed that the products of this 
growth of the cells of the scum were not spherical and nucleated like them, 


* The Pasteur’s solution contained 1 per cent. of alcohol, for reasons with which I need not trouble 
the reader. 


AND OTHER FERMENTATIVE CHANGES 299 


but had the oval and vacuoled character of the scum of the earlier period, so 
that the specific identity of the two growths was no longer doubtful. 

I afterwards obtained still more satisfactory evidence on the same point. 
The long sprouts observed in the scum of the second glass of urine, a few hours 
after inoculation, seemed to indicate that the very liquid which, when altered 
by fermentation, induced the change of the organism to the toruloid condition, 
favoured, when perfectly fresh, a return to the filamentous form. I therefore 
resolved to watch, if possible, the earliest growth of the spherical cells of the 
scum in uncontaminated urine. For this purpose I proceeded on the same 
principle as before ; but experience having shown that the thin layer of atmo- 
sphere between the glass plates was 
exhausted within a few hours, I tried 
a new arrangement for providing a 
larger supply of air, that which I ulti- 
mately arrived at being as follows :— 
A piece of plate-glass about three- 
eighths of an inch thick, and about 23 
inches by 14 in the other dimensions 
(shown in diagram in the accom- 
panying woodcuts, the lower of which 
represents it in section), is excavated 
by the lapidary into a circular ditch, 
D, round a central island, I, the island 
being three-eighths of an inch in diameter, and the ditch or air-chamber of about the 
same breadth, and as deep as the thickness of the glass will conveniently permit, 
viz. about a quarter of an inch. A piece of thin covering glass, P, sufficiently 
large to cover the ditch as well as the island, but not quite so broad as the glass 
plate, so that it can be conveniently sealed down with paraffin, completes the 
‘glass garden’, which is stocked as follows :—The glasses must first be heated 
and allowed to cool, without access of dust to the air-chamber. The glass plate 
with the cover im situ, and covered further with a larger slip of ordinary glass, 
is placed upon a broad plate of metal on a retort stand, and over this a metal 
lid, such as that of a tin biscuit-box. Heat is then applied to the metallic plate 
by means of a Bunsen’s burner or large spirit-lamp, till a drop of water sprinkled 
on the tin lid above passes off at once by ebullition. The lamp is then removed, 
and cooling is allowed to take place completely. The object of the metal plate 
and lid is to diffuse the heat, and thus prevent cracking of the thick and irregu- 
larly shaped plate of glass. The lid above aids in keeping out dust during 
cooling, and this is further effected by the thin covering glass and the overlapping 


300 ON THE GERM THEORY OF PUTREFACTION 


glass slip above that. This slip is also useful in the stocking of the glass garden. 
Having been taken up from the other glasses, it is placed inverted on the table, 
so that the surface which was downwards during the cooling, and therefore 
free from dust, may be directed upwards. A few drops of the new liquid 
medium, in which development is intended to occur, are then placed upon it 
with ‘heated’ pipette, and to these a minute portion of the organism is added 
and diffused thoroughly among the fluid by stirring with a ‘ heated’ glass rod. 
The thin covering glass being now raised by means of ‘ heated’ forceps, aided 
in the manipulations by a ‘ heated’ needle, a very small drop of the mixture of 
organism and medium is placed, by means of the pipette, upon the central 
island of the garden, and, in order to ensure a moist atmosphere in the air- 
chamber, a drop of water, which has been boiled, and cooled under protection 
from dust, is introduced with a clean ‘ heated’ pipette into the ditch... The thin 
covering glass, which has been still held in the purified forceps, is then accurately 
replaced, after which its margins are luted down with paraffin, which is con- 
veniently melted in an egg-spoon, and applied with a clean steel pen heated 
from time to time in the spirit-lamp. This process requires considerable delicacy 
and quickness of manipulation, and constant watchfulness; but with these 
conditions it may be conducted with most satisfactory results; and I have 
watched one and the same organism continuing to grow unmixed in such a 
garden for several weeks together, though carried about with me in a journey 
made in an autumn holiday. 

As soon as the stocking of the garden is completed, it is placed under the 
microscope, and some individual specimens of the organism are sketched by 
camera lucida—a map, on a smaller scale, being also made with the camera to 
enable the observer to find the objects again. 

On the 11th of September I stocked such a garden with a little of the scum 
from the second urine-glass, mixed with uncontaminated urine from one of the 
glasses charged on the roth of August, the liquid still retaining its original bright- 
ness and fresh odour. The cells of the scum thus introduced between the island 
and the covering glass were all of the spherical character, as is illustrated by 
the groups at a in Plate X, sketched at 7.20 p.m., within a few minutes of their 

* The actual order of proceeding is to introduce the boiled water into the air-chamber first, after 
which the same pipette, being clean, may be at once used for the liquid medium. I have found the 
most convenient form of pipette for these experiments to be a small syringe, having its nozzle connected, 
by means of a short piece of caoutchouc tubing, with a glass tube very narrow and thin, so that it is 
almost instantaneously heated nearly to redness by passing it through a flame, and cools with corre- 
sponding rapidity. The tube is bent near its middle at about a right angle ; so that neither the syringe 
nor the hand is held over the experimental glass, while the yielding nature of the caoutchouc junction 


allows the end of the glass tube to be pressed, without risk of breaking, against any object, such as the 
side of a wine-glass, from which an organism is being picked up. 


AND OTHER FERMENTATIVE CHANGES 201 


@) 


introduction. At 9.50 p.m. the nuclei were found more conspicuous and 
altered in position, but there was as yet no change of form in the cells. Early 
next morning I found that the cells generally were sprouting ; but it happened 
that those which I had drawn had shifted their position slightly, so that I could 
not distinguish them in their now altered shape from others in their vicinity, 
but I selected two groups for further observation, represented at 6, and c,, 
sketched at 1.30 and 1.35 a.m. respectively. It will be observed that, while 
this early stage of germination has changed them from the spherical to an oval 
form, they still retain their nucleated character. Five hours later, growth had 
advanced in both groups so as to give the appearance represented at b, and c,, 
In both groups the nuclei have almost disappeared, while the sprouts have 
much increased ; and in c,, while the highest of the three cells has produced 
a short filament, the lowest has formed two oval vacuoled cells, and the 
other, after growing an oval cell, has gone on to the development of a short 
filament. 

After four more hours had passed, I was rejoiced to find the experiment 
crowned with complete success. The longer sprouts of c, had become extended 
to threads of considerable length, as represented in c,; while the progeny of the 
other original cell was in the form of pairs of oval vacuoled bodies destitute of 
nuclei, exactly resembling the constituents of the first scum, or of the granular 
deposits which accompanied the woolly tufts on the first urine-glass. And just 
as in that glass, at an early period, some plants exhibited the filamentous 
others the corpusclar form of growth, so was it with the offspring of the three 
spherical cells whose development we have followed. 

Such was the effect of uncontaminated urine upon this organism. After- 
wards, however, as the liquid gradually became vitiated under its fermenting 
influence, the filamentous form of growth which first appeared began to give 
place again to the corpuscular, a change which the ‘ glass garden’ afforded oppor- 
tunity of watching with perfect precision. c, shows the lower of the two fila- 
ments of c, at 5.50 p.m. on the same day, represented on a smaller scale. It will 
be observed, that, while the filament has increased considerably in length, it 
exhibits a tendency to break up into segments, and here and there along its course 
it has produced oval corpuscles. And a further progress of the same altera- 
tion of habit is exhibited in c,, where the same filament is again sketched on the 
same scale after the lapse of ten hours more, viz. at 3.50 a.m. on the 13th of Sep- 
tember. The filament has only increased very slightly in length, but the terminal 
portion has broken up into segments, and assumed a zigzag form in consequence, 
while a multitude of corpuscles have been produced in the course of the filament, 
partly by budding of the segments of the thread, and partly by the pullulation 


302 ON THE GERM THEORY OF PUTREFACTION 


of the corpuscles themselves, many of which are already of the spherical form. 
And the spherical cells, when examined with a high power, were found to be 
nucleated like those of the last scum. Here and there a plant was found in 
which, in consequence, I presume, of greater vigour, the filamentous growth 
had proceeded further before the corpuscular development occurred, and formed 
septate branches, reproducing exactly the original filamentous form of the 
organism. This is illustrated by d, which represents part of another plant, 
drawn under the high power in the evening of the same day, and introduced 
not only on account of the delicate septate branch which it presented, but 
because nucleated spherical cells were seen to spring directly from little stalks 
on the thicker portion. 

Next day I found one plant so beautifully illustrative of the whole subject 
that I took a sketch of it, which is represented at e, Plate X, the drawing being 
on a much smaller scale, to enable me to include the whole. The plant had 
sprung from a spore situated not far from the edge of the island, and had grown 
towards the air-chamber, and, arriving there, had continued to spread itself 
upon the under surface of the thin glass that formed the roof of the chamber. 
It will be observed that the part of the plant which is most distant from the 
air-chamber has assumed the zigzag form resulting from a tendency to break 
up into segments, and has produced a considerable number of spherical spores. 
Nearer to the air, again, the plant retains its original form, and has very few 
conidia ; while the part in the air-chamber presents the characters of a branched 
filamentous fungus entirely destitute of conidial formation, and this in the 
very same plant which in another part of its course has the loosely jointed 
character with spherical spores. 

But how were these differences in different parts of the plant to be ex- 
plained ? Why did the portion in the air-chamber retain the purely filamentous 
and compact character, while the part on the island and other plants situated 
there became broken up, and produced conidia? The conidial development 
upon the island could not be the result of deficiency of oxygen ; for this mode 
of growth occurred in greatest profusion in the scum of the urine-glass, which 
was freely exposed to air which was being constantly changed. And in point 
of fact, the air in the glass garden was not nearly exhausted at this period ; for 
on examining it again on the 3rd of October, I found that the filamentous form of 
the fungus had by that time grown rampantly over the roof of the air-chamber, 
and had even grown down its walls in some places, and spread upon its floor. 
The obvious explanation appeared to me to be, that the agent which exercised 
the modifying influence upon the growth of the organism was some volatile 
product of fermentation, probably that which assailed the nostrils with a pungent 


AND OTHER FERMENTATIVE CHANGES 303 


stink, and that, where it was evolved in a limited space confined between the 
two plates of glass, it accumulated and produced its effect upon the plants. 
When, on the other hand, it was formed in the very thin film of liquid, which 
alone accompanied the plant on the roof of the air-chamber, it escaped into 
the air as fast as it was produced, and left the fungus unchanged. And this 
view is strongly confirmed by another fact, which I observed at the time when 
the glass garden was stocked (on the 11th of September), viz. that in the first 
urine-glass the filamentous form of growth, which had been entirely suspended 
four days after inoculation, was again present in abundance, forming little woolly 
tufts, which studded the side of the glass. In other words, the urine had been 
restored to a condition compatible with the filamentous mode of development ; 
and the natural explanation of this occurrence is, that the substance which 
exerted the modifying influence upon the organism, stimulating the corpuscular 
while checking the filamentous formation, was a volatile product of fermentation 
of some constituent of the liquid present in limited amount, and that when 
this constituent was exhausted, and the volatile product had escaped, the 
organism was again at liberty to form filaments, as it would have done if placed 
in fresh urine. 

The investigation with the ‘ glass garden’ had thus abundantly proved that 
the filamentous fungus seen in the glass of Pasteur’s solution, the pairs of oval 
vacuoled corpuscles of the primary scum in urine, and the spherical nucleated 
cells of a later period, were one and the same organism, modified by circum- 
stances ; while in the last-named variety we have another example of a plant 
presenting for weeks together the character of a pure and unmixed torula, 
which, had I seen it only in that condition, I should have considered as much 
entitled to that generic name as the yeast plant, yet rigidly demonstrated to be 
a conidial development of a filamentous form. Comparing it with the Torwla 
Ovalis, there is this curious difference between them, that whereas in the latter 
fresh urine is a medium in which the toruloid form especially flourishes, the 
filamentous growth making its appearance in it only when the liquid has been 
altered by the fermenting influence of the organism, the converse is the case 
with this plant. The present species, like the Torula Ovalis, failed to effect the 
ammoniacal fermentation of urea, the contents of the second urine-glass being 
found still sharply acid on the 5thof November, ten weeks afterinoculation. Yet 
it is, as we have seen, an energetic putrefactive ferment of some of the urinary 
constituents, and on this account is attended with considerable interest. And 
as the remarkable naked-eye appearance of the scum which it forms in that 
liquid when altered under its agency, and the toruloid character of the con- 
stituent cells, appear to furnish sufficiently definite specific characters, it seems 


304 ON THE GERM THEORY OF PUTREFACTION 


desirable that it should be named, and I have suggested for it the title Ordiwm 
Torulovdes. 

Some other points observed in the investigation of this plant appear of 
sufficient interest to be placed on record. One is, that the spherical toruloid 
cells of the scum of the second urine-glass, when introduced into a fresh glass 
of Pasteur’s solution, produced none of the purely filamentous growth such as 
resulted from the inoculation of the two previous glasses of that liquid with 
the filamentous form of the organism, any threads met with being only of a very 
loose and imperfect character, like that represented at d, Plate IX, while the 
chief product of the development was pairs of oval vacuoled corpuscles, resem- 
bling those of the scum of the urine at an early period. And the result was 
not only a granular deposit on the side of the glass, but a scum upon the surface, 
whereas neither of the other glasses of Pasteur’s solution had shown any scum. 
This difference between the glasses continued as long as they were kept under 
observation ; that inoculated with the toruloid scum still presenting a growth 
mainly of scum, without any filamentous appearance visible to the naked eye till 
the 14th of September, eighteen days after inoculation, while the other two glasses 
had still no scum whatever, and exhibited abundant conspicuous woolly tufts. 
This fact is of itself proof of a very important general truth, viz. that a particular 
habit of growth impressed upon an organism by temporary residence in a new 
medium may sometimes be retained for a long period after it has been restored 
to its former habitat. The effect of the stale urine upon this plant was to sub- 
stitute the corpuscular for the filamentous mode of development ; and although, 
when returned to the Pasteur’s solution, there was a degree of recovery, as 
indicated by the change from the spherical nucleated cells to the oval vacuoled 
corpuscles, and still more by the occasional appearance of coarse imperfect 
threads, yet the original character was not restored during the eighteen days 
of observation. And this circumstance is the more interesting, when it is 
remembered that the corpuscular variety appeared to differ from the filamentous 
in fermentative power, the former being more energetic in its effects on urine 
than the latter. Facts of this kind may tend to elucidate points of great im- 
portance in the history of contagious diseases, such as the greater virulence of 
such disorders at some periods than at others. For it seems highly probable 
from analogy that the materies morbi may be of the nature of minute organisms ; 
and if this be the case, we can understand, from what we have seen of the plant 
under consideration, that differences of energy in the virus may be occasioned 
by varying circumstances. 

The failure of the plant to resume the filamentous habit when returned to 
Pasteur’s solution, makes it the more remarkable that it should have recovered 


AND OTHER FERMENTATIVE CHANGES 305 


that power in fresh urine, implying that this secretion, when in a perfectly un- 
altered condition, is a still more favourable medium for the organism, permitting 
a degree of recovery which was impossible in Pasteur’s fluid. 

The last fact which I have to mention regarding this plant, is its behaviour 
in an albuminous liquid. This medium, which also proved valuable in experi- 
ments to be described in a later part of this paper, was prepared on the same 
principle as the unboiled urine, by taking the material uncontaminated from its 
natural receptacle, by aid of antiseptic measures. An egg, known to have been 
laid within the last twenty-four hours, was steeped for a while? in a solution of 
carbolic acid in twenty parts of water, to destroy any organisms adhering to 
the shell, and was then broken in a fine spray of carbolic-acid solution of the 
same strength, and about an ounce of the white of the egg was introduced into 
a flask containing ten ounces of water, which had been boiled and allowed to 
cool, the air which entered during cooling having been filtered of dust by a mass 
of cotton-wool tied tightly over the mouth of the vessel before boiling. The 
flask was agitated occasionally during the next twenty-four hours, to promote 
diffusion of the albumen in the water, after which the liquid was passed through 
a boiled filter placed in a ‘heated’ funnel, protected with a ‘heated’ glass 
cover, under a large glass shade.? It was thus cleared of the shreddy residue 
of the white of egg, and also of the opaque floccules resulting from the action of 
the carbolic-acid spray upon the albumen, and was obtained of crystal clearness in 
the ‘heated’ flask into which it was received, and in which it was kept pro- 
tected from dust by a ‘ heated’ glass cap and a glass shade. <A ‘ heated’ wine- 
glass, provided with cover and glass shade as usual, being charged with some 
of this liquid, I inoculated it with a little of the toruloid scum from the second 
wine-glass on the 3rd of September. The result was a corpuscular development 
of a delicate inconspicuous character, the growth proceeding so slowly that the 
little patch of scum, in which alone any increase was observed, had not 
doubled its diameter in ten days. I now introduced with a ‘heated’ needle 
a little piece of the fungus, in the filamentous form, from the first glass 
of Pasteur’s solution. This retained the filamentous mode of growth in the 


* The actual time was much longer than I had intended, viz. two days. A subsequent experi- 
ment, in which one hour and twenty minutes was the period of immersion, was equally successful. Even 
after the two days of the present occasion, the carbolic acid did not seem to have affected the albumen, 
which was free from coagulation to the surface. 

* This was a most troublesome procedure to carry out. I afterwards simplified the process very 
much, so as to dispense with both the spray and the filter, extracting the albumen with ‘ heated ’ pipette 
passed into a hole made in the carbolized shell with ‘ heated’ forceps, a piece’ of carbolized cotton- 
wool being wrapped round the pipette and egg to prevent entrance of dust, filtration of the mixture of 
albumen and water being effected by decanting through a boiled syphon, which had a piece of sponge 
tied over the end in the flask. 

LISTER I D4 


306 ON THE GERM THEORY OF PUTREFACTION 


new habitat, but increased so slowly that after the lapse of six weeks the 
little woolly mass which lay at the bottom of the glass had only grown to 
the height of an eighth of an inch, while the patch of scum was but very 
slightly larger than before, and a mere trace of granular deposit was seen 
upon the glass. 

But though the growth of the organism in this medium had been so ex- 
tremely languid, it had effected a very remarkable change in its constitution, 
the liquid, though still clear, having been altered from its original crystal purity 
to a deep rich brown colour, like that of porter. 

It happened that I had inoculated another glass of this same albuminous 
fluid seven weeks previously with another very delicate filamentous fungus, 
which I must not here describe. The species had developed very luxuriantly, 
so as to occupy the greater part of the liquid with its white woolly growth, and 
clamber some distance up the inside of the glass above. Yet the colour of the 
fluid was scarcely altered at all, having a barely perceptible pale brownish 
tinge, and this circumstance made the great effect of the scanty growth of the 
Oidium Toruloides the more striking. At the same time, the dark brown liquid 
was entirely destitute of odour, and thus I obtained for the first time demon- 
stration of what I have long suspected, as the result of experience in antiseptic 
surgery, viz. that an albuminous fluid may be affected with a fermentative 
change without the occurrence of smell. I have seen, for example, a psoas 
abscess furnish merely a slight oozing of serous discharge under antiseptic 
management, till a single careless application of the dressing admitted, as I 
believed, some fermentative organism, which, without giving rise to any odour, 
so altered the character of the discharge, as to stimulate the diseased part to 
profuse suppuration, leading to death by hectic. I have also observed erysipelas 
occur in spite of antiseptic treatment, and occasion profuse suppuration without 
smell, although from analogy there is reason to suspect that the virus of that 
disorder is of the nature of an organism, operating as a ferment upon the animal 
fluids. Facts such as these had often led me to express the view which at the 
time might be regarded as transcendental, but which the above observation 
proved to be a truth. 

Thus this single insignificant species, when subjected to the precise method 
of investigation which I have described, afforded proof of several important 
general truths, which may thus be recapitulated. 

1. It shows how greatly such organisms may vary under the modifying 
influence of different media. 

2. It affords another clear example of the origin of a torula from a fila- 
mentous fungus. 


AND OTHER FERMENTATIVE CHANGES 307 


3. It shows that the corpuscular form of such an organism may differ in 
fermentative energy from its filamentous parent. 

4. That the corpuscular habit of growth acquired in one medium may be 
retained for a considerable time after the organism has been restored to a habitat 
in which the corpuscular form did not originally present itself. 

5. That when placed in a more favourable medium, the toruloid variety 
may reproduce the purely filamentous. 

6. This plant is another instance of an organism which is not bacteric, 
giving rise to a putrefactive fermentation in urine. 

7. It proves that an albuminous liquid may be affected with a fermentation 
with inodorous products. 

Lastly, The trustworthiness of the method of investigation is strikingly 
confirmed by the fact, that in none of the glasses of Pasteur’s solution, urine, 
or albuminous fluid inoculated with this oidium, and in neither of the glass 
gardens, did bacteria, or any other kind of fungus besides the one intentionally 
introduced, make their appearance during the entire month in which the obser- 
vations were made. 


308 ON THE GERM THEORY OF PUTREFACTION 


EXPLANATION OF PLATES VI TO X 


PLATE VI 


Fig. 1, a pencil of fructifying threads of the common blue mould Penicillium Glaucum. 

Fig. 2, a group of cells of the yeast plant, Torula Cerevistae. 

Fig. 3, Bacteria from various sources. The pair below the letter a are examples of a granular appear- 
ance of the protoplasm, and the presence of a distinct nucleus in each segment. 6 a Leptothrix 
filament, some of the segments being nucleated. 

Fig. 4 illustrates the ordinary mode of growth of Bacteria, viz. by increase of the segments length- 
wise and transverse segmentation. When first sketched, at 7.30 a.m., the object consisted of 
three segments, a, c,, b,. During the few minutes that elapsed between the completion of this 
sketch, and that at 7.42 a.m., the uppermost segment 0, is seen to have increased in length to 
the size shown at b,, and the two lower ones are not only longer, but each presents a transverse 
line of segmentation, while the middle segment is bent at this new place of division, c,. Three 
minutes later the three lowest of the five segments of which the object now consisted separated 
from the other two, and in the sketch taken at 7.48 they are shown thus detached, the lower 
two obviously increased in length. Two minutes later one of these three was found to have 
separated and moved off, and the remaining pair were observed to swim away as an ordinary 
double bacterium. 

Fig. 5 represents a minute organism, consisting of granules grouped in a different manner from 
that which commonly prevails among Bacteria. The difference of arrangement is explained 
by difference in the mode of growth, as is illustrated by the sketches ¢,, c,, cs, and c,, which repre- 
sent the same granules in process of fissiparous generation. It will be observed that the granules, 
instead of increasing like ordinary Bacteria in one direction only, swell up in all dimensions and 
afterwards undergo segmentation, either into pairs or into fours, as indicated in the letterpress, 
p- 281. 

Fig. 6 represents a form of Torula which resulted from the mingling of a drop of rain with fresh 
uncontaminated urine. Appearing in the first instance as an unmixed Torula (a), it changed 
in course of time to a delicate filamentous fungus (b and c) bearing buds, some of which were 
more or less toruloid in aspect and habit of growth, while others were morphologically identical 
with Bacteria, as described in detail in the text. 


PLaTE VII 


represents the same organism (Torula Ovalis), varying in character according to the medium in which 
it grows, and the period during which it has inhabited it. For a detailed description, see letter- 
press. 


Piates VIII, IX, anp X 


show a minute fungus varying according to its habitat, from a filamentous growth to Torulae of very 
different characters, all distinctly traced to one and the same organism. For a detailed descrip- 
tion, see letterpress. 


These illustrations are all taken from camera-lucida sketches, the magnifying power being 1,140 
diameters, except in some cases where it is lower, as indicated by the scales on the plates. 


| : Ciara vl 
Torula’ Cerevisice’ Bacterta’ 


from vartous sources 


>. 0 
2? ® r }) 0 ; 
GT DGsz,, - 
pe DP Rh 


Bacteria’ growing 


ane 


o 
| / J | 
| ri } 
Lt oc 4) ji 


la | ae ‘ 


/ 
/. 30am. 7.42 am / a 


Fig. 5. Cr POAMUMG EAD. 


: : , ; : : : 3 ; 

F In boiled Urine. | In unbotled’ Urine ‘\Growiung uv Urave diluted with 

‘4 1 ‘ 

ye 9 ! 
f f ' ie 8 is ; RB } 
/ / y | : 6b, 800 % : &? oo ge Qos] 
if 29 % 20 ° 1 OP = - C, Oe , 

Es fe) ° fey ' er fe) : ‘ 0 
fe) ° ! ¢ \ - 

ea : V% qe ; ‘© So S55am Gham 2 30am 13 


Fig 6.  Llorula Ovats. 
Iv Urine 18 lv Dec,” 1871. ! In the same glass of Orine 9 Aug 1872. 


{ Ct Scale in Ten-thousandths of av Lrebv 
bs 2 
ee —— = ns 


delt Vincent Brooks Day & Son 


Plate VII 


| | Ti O rula O valis conbiuied) 
tv Pastears Solution 3O LD oe [bil : After eight months wv Pasteurs Solution, 9 An) 
Az, Cy | 


' 
i 
' 
! 
| 
\ 
! 
' 
I 
1 
t 
' 
\ 
i 


' 
' 
t 
! 


Offspring of the same specemen wv fresh Urine; 14 WY Nov. 1873. ‘Ivtreshy Pasteur’ Sol 
18 # Nov: 1873 


é oO 

S@) 
oO 

= / f 

\ x] Ae 

/ a °) 
(ery ler 
ce — 


0123 +5 Scale in Ten-thousandths of an Inch 


} _ Lister, del. Vincent Brooks Day 


PlateVII. 


Oidiam  Toruloides 


tv fresh Pasteur's Solution, Glass N° 


tructifying tilament 
/ wv glass of stale Pasteurs Solaltorv 


examined’ uv WNater. 


xD Y Ang. 1/6 Ye Aug. 
Pa) pe diets wm 7 4D pm: 


ad, Qs, 
V0 | Lv fresh Pasteurs Solattor, Glass N°&2 
\ 


O77 234 5 (ff 
: l LY 
9 2 


Ene a! eae eel a oT L 
Scale iv Ten thousandths | / 0 f 2 ‘ 
NX y = ——— SS SS 
er eee = oD) ate Thousandths of an Inch 
\Y oy ) 
\ } 

ae a } noe a eee a ARES 
nt Broo lay & SonLt 


del 


— | Plate 1X. 


Oidim Torulotdes continued 
Tw Urine, Glass N° inoculated 2/%¢ Aug. 


Xe Hh eteane 
SES ‘@ i: BO OX 


> 


oe 


SQ?) 
<3) m4 . thy 
26% Aug. 9.30 a.m. 26 5 Aug. 7 p.m. a7, Aug. 12 p.m, 
The Torulotd: form changing whem transfered) to Pasteurs So 


©) (9 


Plate 1X. 


O CATT Le Or ulo LACS continued 
Tw Urine, Glass Nl inoculated 2/%* Aug. 


oe: 


2h W Aug. 8 pt. ao Aug 6 p. 1, 


oe : CIO 
IC VS / ): 
1oys 6 O- £6 
26% Aug. 7 p.m. 
The Torulotd: form chang when tran sfered) to Pasteurs Soluti 
Q © 


a £ 
w~G) o~ ». De 
wv, Oran m oN Ys ra 
wa Ca mers +4 

\ oa) f 


9) ») c: 
L/ p.nv. pm & ‘N 
re _ SS Jl ‘Aug 
C1 tt tt Scale tr lev-thousandths of av Inch 7 4S am 


Vincent Brooks Day & £ 


— —— 


AS PUR THER CONTRIBUTION TO THE NATURAL 
HISTORY OF BACTERIA AND THE GERM 
THEORY OF FERMENTATIVE CHANGES 


[Quarterly Journal of Microscopical Science, October 1873.] 


In April of this year I communicated to the Royal Society of Edinburgh 
some of the results of a protracted investigation into various circumstances 
connected with the appearance and growth of minute organisms in fermentable 
substances. During the time that has since elapsed I have continued to pro- 
secute the inquiry, and have obtained various new and striking confirmatory 
facts, a selection from which will form the subject of the present paper. 

In the former communication observations were related which led me to 
conclude that in some minute species of hyphomycetous fungi, the spores (conidia) 
produced upon their filamentous branches germinate in three distinct ways ; 
first, they may form comparatively thick sprouts, which become young plants, 
like the parent ; second, they may multiply by pullulation like the yeast plant, 
and under some circumstances this toruloid growth? may continue for an in- 
definite period, though the resulting progeny will, under favouring conditions, 
reproduce a fungus like the original; and, thirdly, the conidia may shoot out 
sprouts of exquisite delicacy which break up into bacteria. In accordance 
with this mode of origin of bacteria it was shown that such organisms, like 
the fungi from which they are derived, are of various totally distinct kinds, 
manifesting their differences both morphologically and still more physiologically 
by the characters of the fermentative changes to which they give rise, and by 
the circumstance that some sorts refuse to grow at all in media in which others 
thrive. Some of the species exhibited most remarkable variations in size, 
form, and movement when introduced into different media, and sometimes 
gave indications of their fungoid origin by indubitable branching, and, in the 
thicker forms, by the presence of nuclei or vacuoles. Yet, however much any 
such modification might differ from the form in which the species was seen in 
another medium, the latter variety could be reproduced at pleasure by reintro- 
duction into the habitat in which it was originally seen. 

Hence any classification of bacteria hitherto made, from that of Ehrenberg 


’ Printed at page 275 of this volume. 
* Considering the differences among authors in the use of the term torula, it seems justifiable for 
the sake of convenience to retain the old sense, as applicable to organisms like the yeast plant. 


310 A FURTHER CONTRIBUTION TO THE 


to that of Cohn,! based upon absolute morphological characters, is entirely 
untrustworthy. In order to determine the species of any particular specimen 
it is necessary to take into account not merely its appearance, but also the 
character of the medium in which it occurs. Even then mere morphology will 
often entirely fail us unless we are able to ascertain the physiological characters. 
And even these appear by no means constant ; for we shall in the present paper 
see reason to believe that one and the same bacterium may differ at different 
times in its fermentative effects on one and the same organic solution. 

It is obvious that to trace the modifications of any one such organism 
through a series of successive habitats would be an utter impossibility if bacteria 
or any kind of fungi were liable to be evolved from the mere chemical con- 
stituents of the liquids employed; and thus the investigation, though not 
undertaken for the purpose of combating the doctrine of spontaneous generation, 
has afforded the strongest possible evidence against it, and in favour of the 
germ theory of fermentative changes. For even in organic liquids such as 
milk, in which spontaneous generation has been said to be most liable to occur, 
it required only a rigorous attention to experimental details to ensure the com- 
plete absence of either organic development or fermentative change, except 
where organisms were intentionally introduced. But when this was done, the 
particular species used for inoculation grew unmixed with others, attended by 
the chemical alterations characteristic of it. 

In order to enable the reader to give credence to my statements, it is essential 
that I should describe in detail the mode of procedure in its most improved 
form. Let us take, as an example, the case of boiled milk. The first thing 
to be done is to ensure that the interior of the vessel in which the liquid is to 
be heated shall be free from any living organisms. This is done by subjecting 
a Florence flask to a very high temperature, after providing that the air which 
enters on cooling shall be effectually filtered of living dust by passing through 
asbestos which, I find, answers this purpose quite satisfactorily. The asbestos 
is placed, in a mass about a quarter of an inch thick, between two layers of tin- 
foil sufficiently broad and long for wrapping round the junction of the neck 
of the flask and a glass cap that covers its mouth ; and when it has been so 
arranged, fine iron wire is tied tightly round, so as to compress it firmly as well 
as retain it in position after the outer layer of tinfoil has been dissipated by 


* It is, however, only just to Professor Cohn to state that he dwells largely upon the different : 
physiological effects of different supposed species of bacteria, and sometimes makes them a ground 
of classification, more especially in the group of ‘ pigment bacteria ’, which he distinguishes from others 
on account of the remarkable colouring matters to which they give rise. Nevertheless he relies in the 
main on absolute morphological characters. See ‘ Untersuchungen iiber Bacterien ’, von Dr. Ferdinand 
Cohn. Beitrdge zur Biologie der Pflanzen, Zweites Heft, Breslau, 1872. 


GERM THEORY OF FERMENTATIVE CHANGES 311 


fusion and oxidation. The flask, previously mounted in strong wire for con- 
venience of holding with forceps and for suspension, is then roasted thoroughly 
over a large Bunsen’s burner and hung up by its wire mounting to cool. 

The next point is to introduce the milk without contaminating any part of 
the flask except the lower portion that receives the liquid. For this purpose 
a funnel is used sufficiently long to reach from some distance above the mouth 
of the flask to its bottom ; and the exterior of the tubular part of the funnel is 
freed from living organisms by wiping it with a cloth, soaked in a strong watery 
solution of carbolic acid (one part of the acid to twenty of water), and drying 
it with a carbolized rag prepared by immersing it in a solution of one part of 
the acid in a hundred parts of anhydrous sulphuric ether and allowing the ether 
to evaporate. 

This is much more convenient than heating the thick glass of the funnel, 
as I did in my earlier experiments ; and I may add that throughout this investi- 
gation I have found great advantage from thus substituting the use of chemical 
antiseptic means for the employment of a high temperature when the former 
happens to be more convenient. And I may remark incidentally that the 
results have afforded most conclusive evidence of the efficiency of a strong watery 
solution of carbolic acid for destroying minute organisms ; for throughout the 
whole course of the experiments I have found cleansing with such a lotion exactly 
on a par in this respect with exposure to the gas flame. 

The tube of the funnel, thus freed externally from living germs, is passed 
down to the bottom of the flask, the asbestos having been previously removed 
and the glass cap lifted after wiping its margin with carbolic lotion for the chance 
of any organism having been applied to it in the process, and a piece of car- 
bolized rag being wrapped round the mouth of the flask and the funnel to exclude 
living dust, the milk is poured in so as to fill not more than the lower half of the 
body of the flask. The funnel is then withdrawn through the rag, scrupulous 
care being taken that its extremity, now contaminated with the milk, does not 
touch the side of the flask. A substantial piece of cotton-wool carbolized in 
the manner above described is then tied over the mouth of the flask to filter 
any air that may regurgitate during the next stage of the process, the heating 
of the milk. This is done by immersing the body of the flask in a saucepan of 
boiling water and retaining it there for about an hour, care being taken that the 
boiling water never sinks below the level of the milk. By this means we are 
sure that the milk has been throughout exposed to the temperature of 212° Fahr. 
for the period desired, while the earlier parts of the process give us equal assur- 
ance that the whole interior of the flask above the milk is free from living 
organisms. The immersion of the flask in a bath of boiling water, for which 


312 A FURTHER CONTRIBUTION TO THE 


I am indebted to a suggestion of Mr. Godlee, of University College, London, 
has three advantages over boiling by direct flame; it avoids frothing, which 
in the case of milk is extremely troublesome, and also the sputtering to which 
Dr. Roberts, of Manchester, has drawn attention ;1 it prevents any loss of 
water by evaporation, and so disposes of the vexatious question of whether the 
specific gravity of the liquid has not been so raised as to render it unfavourable 
for organic development ; and lastly, it avoids any ‘ burning’ of the milk with 
its accompanying chemical changes. 

The milk having been allowed to cool completely, a portion of it is decanted 
off into experimental glasses. These are plain ‘ liqueur-glasses ’, each provided 
with a glass cap shaped like a small evaporating dish (made to order at any 
glass work) and covered with a small glass shade standing on a square piece of 
plate-glass. The glass plate has the double advantage of allowing the glass 
to be removed without disturbing the glass shade, and also of preventing the 
air beneath the shade from acquiring an accidental odour such as is derived 
from wood or other porous substances, and interferes with judging of chemical 
changes by the sense of smell. 

The glass shade and glass cap have in combination the effect of perfectly 
excluding all living dust, although, as neither cap nor shade is made to fit 
closely, a constant free interchange by diffusion between the air in the liqueur- 
glass and the gases of the atmosphere is permitted. Hence, provided always 
that the liqueur-glass and its cap are free from living organisms to begin with, 
and that the contained liquid is similarly circumstanced, the latter will remain 
for an indefinite period unchanged except by gradual loss from evaporation, 
till at length in the course of months it dries up into a solid mass. 

Further I have found as a matter of experience that if the glass shade and 
cap are raised, in a part of the room free from draughts, for the purpose of 
inoculation of the liquid or withdrawal of a small quantity for examination, 
there is practically no risk of the accidental introduction of organisms, provided 
of course that the operations be nimbly executed and that any piece of apparatus 
introduced into the glass have been suitably purified. For it appears that 
organic germs are not nearly so abundant in the atmosphere as is sometimes 
assumed, and only a very small fraction of the portions of dust with which the 
air of an occupied room is loaded have such germs adhering to them. Thus, 
in one instance the sole result of exposure of a glass of uncontaminated urine 
for half an hour in my study was three plants of three different kinds of fila- 
mentous fungi, each growing from one point and enlarging thence in all directions, 
while the liquid remained otherwise unchanged in aspect, a fact which may 


* See Nature, February 20, 1873. 


GERM THEORY OF FERMENTATIVE CHANGES 313 


probably be stated equally truly by saying that, of all the many particles of 
dust that fell in during that period, only three at most contained a germ capable 
of growing in urine. 

Hence while it is most true that scrupulous care must be taken in these 
experiments, and that forgetfulness or slovenliness in their execution would be 
absolutely fatal to success, yet it is equally true that by the very simple means 
which I am now describing the observations may be made with a facility and 
precision that leave nothing to be desired. 

The glass plate and shade are simply washed and dried with a towel, but 
the liqueur-glass and its cap must be purified by heat like the flask. This is 
very simply done by bringing both to a high temperature over two spirit-lamps 
or Bunsen’s burners, the liqueur-glass being held in the hand by its foot and 
the cap in a pair of forceps; and the cap having then been placed on the glass, 
a substantial piece of cotton-wool with a bit of muslin beneath it (neither car- 
bolized) is placed on the cap and tied firmly with fine iron wire round the glass 
beneath. The heat of the glasses ensures the destruction of organisms in the 
part of the cotton, which acts as a perfect filter during cooling; and though 
the muslin may be browned by the high temperature, no empyreumatic odour 
is occasioned in the glass nor any deposit on its sides! The glasses having 
cooled, the wire ligature is cut and the cotton carefully removed, the muslin 
beneath serving the purpose of clearing off all portions of cotton at once, and 
the glass and cap are immediately placed on the glass plate beneath the shade. 

A series of experimental glasses, say a dozen, having been thus prepared, 
it remains to charge them by decanting from the flask, and this is a matter 
which, at the risk of appearing tedious, I am compelled to describe in minute 
detail. 

The process is effected by means of a syphon of glass tube with a calibre 
of about one-eighth of an inch, the shorter leg rather longer than the height 
of the flask, and the other leg four or five inches longer. I find the most con- 
venient way of purifying the syphon is to boil it, and in order to adapt it for 
packing into a saucepan, the glass tube is interrupted at intervals of about 
four inches with pieces of caoutchouc tubing, the shorter leg having one such 
india-rubber hinge, and the longer leg two. They are tied firmly on the tube 
with fine wire, silver wire being used for the shorter leg, where iron must rust. 
In the longer leg one of the caoutchouc junctions serves the further important 
purpose of enabling the assistant to control the flow through the syphon by 
compressing the india-rubber between the finger and thumb. A fourth piece 


* It is only in my more recent experiments that I have thus employed the cotton, but there can be 
no doubt that while it scarcely adds to the trouble of the process, it must materially increase its security. 


314 A FURTHER CONTRIBUTION TO THE 


of caoutchouc tubing is applied, without tying, to the end of the longer leg, 
for adapting a syringe. The syphon thus constructed is filled with water and 
boiled for half an hour, and while it is still in the hot water, one of the caoutchouc 
junctions of the longer leg is seized with catch forceps (previously heated) to 
prevent the syphon from emptying itself when taken out. The longer leg being 
now raised from the saucepan by aid of another pair of heated forceps, the 
syringe, which has been washed out with carbolic lotion, and the nozzle passed 
through the flame, is applied to the terminal caoutchouc adapter. The shorter 
leg is next raised, and at once slipped through a hole in the middle of a piece 
of carbolized cotton-wool, and then into the flask (whose cotton cap has been 
previously loosened, so as to be ready for removal), and the end of the leg being 
kept a little above the level of the liquid, to avoid mingling of the water in the 
syphon with it, the cotton is tied round the neck of the flask and the syphon. 
Then, as the syphon is intended to be left permanently adapted to the flask 
to serve for future decantings, it is needful to provide against the access of 
organisms to the moisture between the india-rubber junctions of the longer leg 
and the glass tube. For this purpose, the catch forceps being removed, car- 
bolized cotton-wool is wrapped round each junction, and a piece of rag over 
this to enable it to resist wear, and tied securely round the glass tube above 
and below the caoutchouc. The syphon is now emptied of its water by means 
of the syringe, and the shorter leg being pushed down till its extremity is in the 
liquid, the syringe is again brought into operation till the syphon is seen to be 
full of milk. The assistant then compresses one of the caoutchouc junctions 
through its cotton investment, to prevent the milk flowing out when the syringe 
and its adapter are removed. This is done with fingers dipped in the carbolic 
lotion, and the apparatus is completed by slipping upon the glass tube that 
now terminates the syphon a circular piece of thin caoutchouc, about two inches 
in diameter, with a hole in the centre just large enough to admit the tube, 
so that it remains in position without further fixing. This caoutchouc plate 
is to serve as a screen to keep dust out of the glasses while they are being filled. 
To keep it level it is strengthened by a fine wire run through and through near 
its margin, and, to ensure freedom from living organisms, it is steeped for half 
an hour or so in the strong carbolic lotion ; after which, as caoutchouc has the 
property of imbibing carbolic acid into its substance, the screen when dried 
retains a sufficient quantity of it to ensure the destruction of organisms that may 
come in contact with it. The experimental glasses, which as yet:are covered 
with their shades at as short a distance as possible from the syphon, are suc- 
cessively exposed and charged, each being brought close to the syphon before 
the glass cap is raised, and then at once placed with its margin in contact with 


GERM THEORY OF FERMENTATIVE CHANGES 315 


the caoutchouc screen, while the end of the syphon extends into the glass. 
The assistant is now directed to relax his hold upon the caoutchouc junction 
above, when the milk at once flows into the glass, and when this is about two- 
thirds filled, the flow is again arrested by the assistant, the glass removed, the 
cap, held in the other hand of the operator, is reapplied, and the glass placed 
again under cover of the shade. 

All the glasses having been charged, the caoutchouc screen is slipped off 
and a piece of carbolized cotton tied over the end of the syphon, which being 
raised to a higher level than the fluid in the flask the assistant finally relaxes 
his hold and the syphon empties itself into the flask, becoming occupied by air 
filtered by the cotton tied over the extremity. When at any future time another 
set of glasses are to be charged, all that is needful is to remove the cotton-wool 
from the end of the syphon, re-adapt the syringe by means of a caoutchouc 
adapter, steeped for a short time in carbolic lotion, and then proceed as before. 
In this way we avoid the great loss of time involved in providing a fresh syphon 
for every fresh decanting, as I did in the earlier experiments. 

The other experimental fluids employed in the observations about to be 
related were Pasteur’s solution, turnip infusion, an ‘artificial milk’, consisting 
of a solution of sugar of milk and white of egg in water, and urine. 

In preparing the Pasteur’s solution for this set of experiments I deviated 
from Pasteur’s formula in two respects; viz. the proportion of the water and 
the source of the mineral salts. I doubled the quantity of water, so as to make 
the liquid, as I hoped, more favourable for the growth of some organisms, more 
especially after loss by protracted evaporation as occurs in my experiments, 
and tap water was employed instead of distilled, so as to afford greater variety 
of saline material. For the yeast ash, which every one who has tried must 
have found extremely troublesome to prepare, I substituted the same weight 
of ashes left after burning a large amount of loppings from various kinds of 
trees and shrubs ; the liquid obtained by lixiviation being filtered, and a quantity 
used in proportion to the estimated weight of dissolved solids. It seemed to me 
that the salts obtained in this way would be more likely to afford suitable 
pabulum for the growth of different organisms than those derived from one 
particular species of fungus. Thus, my Pasteur’s solution had the following 
composition :— 


Water from the tap. ; . 5000 grains 
Lump sugar ae ; : r w250-* 4. 
Tartrate of ammonia . BOs! 
Salts from wood ashes . . , Da 


It happened that the alkalinity of the ashes exactly counterbalanced the acidity 


316 A FURTHER CONTRIBUTION TO THE 


of my specimen of tartrate of ammonia, so that I had a perfectly neutral solution 
to work with. The flask was prepared and the fluid introduced as above 
described for milk, but the boiling was done by the direct flame and was con- 
tinued only ten minutes. 

The turnip infusion was prepared by boiling peeled white turnips, in about 
enough water to cover them, till they were soft, reducing each to a mash with 
a little additional water, filtering, and keeping the filtrate at 212° Fahr, for 
half an hour, as in the case of the milk. 

The ‘ artificial milk ’ required special preparation. A solution of 160 grains 
of milk-sugar in ten ounces of tap water, which is about the proportion in milk 
according to Miller’s Chemistry, was subjected to the temperature of 212° Fahr. 
for an hour and a quarter in a flask prepared and arranged as for the milk. 
Next day, the fluid being of course cold, I added five drachms of the white of 
a raw egg, the shell of which had been treated twelve days before with one 
to twenty carbolic-acid solution for an hour and twenty minutes and then 
wrapped in carbolized cotton, a process which, I may remark, preserves eggs 
from putrefaction, apparently for an unlimited period, although the carbolic 
acid leaves the cotton in a few days, and that which was applied to the egg- 
shell does not penetrate sufficiently to produce any coagulation whatever of 
the albumen ; and I have lately eaten an egg which had been prepared in this 
manner more than three months before, and for the last fortnight had been 
kept at 100° Fahr. A large pipette having been purified by heat, and protected 
from the entrance of dust in cooling by means of carbolized cotton, a plug of 
which in the upper end served the further purpose of preventing the entrance 
of organisms into it from a syringe with which it was connected by means of 
a caoutchouc adapter, a small hole was made in the shell of the egg with car- 
bolized fingers and heated knife, and the narrow end of the pipette being inserted 
between the yolk and the shell, and a piece of carbolized cotton wrapped round 
the pipette so as to cover the orifice and exclude dust, almost all the white was 
extracted without interfering with the yolk, and transferred at once to the sugar- 
of-milk solution in the flask, the cotton round the pipette serving as a temporary 
screen, for which a substantial cap of the same material was substituted on 
removal of the pipette. Twenty-four hours later, the flask having in the interval 
been occasionally agitated to diffuse the albumen, a syphon was introduced 
with the peculiarity that a piece of sponge was tied over the end of the shorter 
leg to serve as a filter for excluding the shreddy undissolved residue of the 
albumen, the sponge being of course purified by the boiling. The artificial 
milk was thus obtained with only trifling turbidity when decanted into 
experimental glasses, and the stock in the flask has remained unchanged 


GERM THEORY OF FERMENTATIVE CHANGES 317 


to the present time (September 1873), more than three months after it was 
prepared. 

The urine was not boiled at all, but was obtained altogether unaltered by 
a very simple process, depending upon what appears to be a fact of high interest 
both physiologically and pathologically, that a mucous canal in a state of health 
does not permit the growth of foreign organisms in its immediate vicinity, so 
that preliminary external application of a carbolic lotion (1 to 40) is sufficient 
to ensure an uncontaminated state of the fluid, which, with its unaltered mucus, 
is a much more favourable nidus for organic development than after boiling. 

One other piece of apparatus requires a short notice, viz. that used for 
withdrawing fluid from the experimental glasses for inoculation or examination. 
The most convenient means for this purpose I have found to be what may be 
called a ‘syringe pipette’, consisting of a small syringe with a piece of glass 
tube connected with it by a caoutchouc adapter, the junction being self-support- 
ing but yielding (as distinguished from rigid). This last property permits the 
use of a very delicate tube without risk of breakage when it touches the side 
of a glass; and it is of great importance that the tube should be of as thin glass 
as possible. It can then be heated fully when dry by once drawing it quickly 
through the flame of a Bunsen’s burner, and a few seconds suffice for its cooling. 
The tube, which is about a line in diameter, is drawn out a little at the end, 
and is bent at an obtuse angle about two inches from the syringe ; so that the 
latter is not held over the liquid during the process. Care is taken not to drive 
any air from the syringe into the tube after heating the latter, and rather more 
of the liquid than would suffice for inoculation is taken up, so that the part left 
in the tube may protect that which is ejected from air from the syringe. 

To the general reader these details may seem almost unpardonably minute, 
but for any one who is desirous to repeat similar experiments I venture to hope 
they will not be found so. 

On the 14th of June I drew off for the first time some milk from the flask 
which was exhibited to the Royal Society of Edinburgh in April as having its 
contents still fluid, and therefore probably unaltered, though prepared seven weeks 
previously, and under difficulties as compared with the material of later experi- 
ments, inasmuch as it was boiled by the direct flame of the lamp, the extreme 
inconvenience occasioned by the frothing of this flask having led to the sug- 
gestion of the boiling-water bath above described. Also the cotton-wool over 
the mouth was not carbolized, a piece of muslin between the cotton and the 
flask being alone treated with the ethereal solution of the acid. Nevertheless, 
the cotton filter had proved efficient in spite of the often repeated rapid rushing 
of air into the flask which must, of course, have occurred whenever the lamp 


318 A FURTHER CONTRIBUTION TO THE 


was removed to prevent the froth from reaching the cotton. For the milk 
when decanted just four months after the boiling, proved perfectly good, having 
a slight flavour of turnip as might be expected of winter milk; its reaction 
showed the peculiar character now known to be possessed by that fluid when 
fresh, purpling blue as well as red litmus paper, and the microscope showed no 
appearance of organisms or of the granular masses of deposited caseine often 
seen as an early indication of fermentative change, while the milk globules were 
bright and unaltered. 

These observations were made upon the first two or three drachms that 
flowed from the syphon, received into an unprepared glass, as should always 
be done to wash out any residual water from the tube, and thus ensure uni- 
formity of the contents of the experimental glasses. Of the latter, one was at 
once exposed in my study by removing the shade and glass cap to receive any 
organisms that might fall into it, and was covered again with cap and shade 
after fourteen hours, including the night and early morning in which the furniture 
was ‘ dusted’ with a cloth by the servant, but the glass carefully avoided. It 
was then placed beside the other glasses in a cupboard, the temperature of 
which varied from about 65° to 70° Fahr. 

On the 2oth of the month I observed for the first time a delicate filamentous 
fungus on one part of the side of the glass, extending upwards from the milk 
for about an eighth of an inch; and at the same time a semitransparent layer 
which had been noticed for about two days previously at the surface of the 
milk was found to have increased in thickness. Two days later this layer had 
attained a depth of one-sixth of an inch, and I proceeded to investigate its nature, 
thinking it probable that it might be a change induced by the growth of the 
fungus. But on trying to take up a portion with the syringe pipette, I en- 
countered a most unexpected difficulty in extreme viscidity of the liquid. I had 
before observed the effects produced upon milk by thirteen different organisms, 
including six distinct kinds of bacteria, but though the products had differed 
extraordinarily in colour, reaction, and consistence viscidity had in no case 
been witnessed. Here, however, the upper part of the milk had been con- 
verted into the most viscid substance I ever saw. When I at length succeeded 
in extracting the pipette without any of its contents getting upon the outside 
of the glass, I found that on touching any object with the delicate end of the 
tube and withdrawing it, the tiny drop became extended into a thread a foot 
and a quarter in length, as delicate as the finest spider’s web and barely visible 
from its tenuity. I afterwards amused myself with spinning webs from one 
object to another. When dry they exhibited considerable tenacity, and thicker 
ones broke with an audible snap when subjected to longitudinal traction, while 


GERM THEORY OF FERMENTATIVE CHANGES 319 


the finer ones floated like gossamer in the air. Here, then, was an amazing 
chemical change effected in the milk, and one of great interest with reference 
to the elaboration of mucus and other viscid secretions in the animal economy. 
On applying the microscope I found no fungus filaments, but multitudes of 
motionless bacteria, such as are represented in Plate XI m, very minute and 
delicate, and often showing a peculiarity only badly represented in the specimens 
drawn, viz. that of having one part of the organism of much higher refractive 
power than the rest. In the lower part of the glass similar bacteria were seen 
in active movement, often curiously wriggling and sometimes rotating com- 
pletely round a transverse axis. The reaction of the milk was also changed, 
distinctly reddening blue litmus paper and not affecting red. 

Next day I introduced into another of the glasses of milk a morsel of the 
viscid substance by means of a pair of mounted needles passed through the 
flame. A glass of the artificial milk above described, which had been decanted 
for seventeen days and had undergone no change, and a glass from a flask of 
Pasteur’s solution which had been prepared on the 11th of February, and 
remained brilliantly clear, were also similarly inoculated. 

In the course of two days observing a translucent layer, about a line in 
thickness, at the top of the milk in the second glass, I removed some for examina- 
tion. It was distinctly acid in reaction but uncoagulated, and when a drop 
was diffused on a glass plate the liquid was seen to be generally thin and 
turbid, but studded with transparent specks which, when touched with the 
point of a needle, could be drawn out into threads like the viscid material of 
the first glass. On applying the microscope to one of the transparent specks, 
multitudes of motionless bacteria were seen, such as are represented at 0, 
Plate XI, showing in a striking manner the peculiarity before described, of 
having their extremities of different refractive power from the rest. The thin 
turbid part, on the other hand, was a finely granular fluid in which similar 
bacteria were seen in much smaller numbers, some of them moving freely, 
while others were motionless, the latter being each surrounded with a trans- 
parent halo of greater or less extent as is shown at # and g, Plate XI, and in 
some cases, the transparent areas surrounding different bacteria were confluent. 
These were evidently miniatures of the transparent specks visible to the naked 
eye ; and they seem to me beautiful examples of a change effected by bacteria in 
the surrounding medium, whether due to vital action of the organism or to some 
substance (a so-called chemical ferment) emitted from it during life or after death. 

The moving bacteria, it is to be remarked, had no transparent area around 
them, nor were they able to penetrate those that surrounded the motionless 
ones, proving the substantial character of the latter. 


320 A FURTHER CONTRIBUTION TO THE 


The artificial milk and Pasteur’s solution were turbid the day after inocu- 
lation: and in the former, which I examined microscopically, were seen active 
bacteria of extreme minuteness, looking like mere pairs of granules, which on 
the following day had given place to others of larger size and of the same sort 
of characters as those of the milk, as shown at m, Plate XI. Similar bacteria 
were also seen at this time in the Pasteur’s solution. But neither then nor at 
any subsequent period was there any viscidity of the general liquid in either 
of these glasses, implying that the viscid substance was no essential appen- 
dage of the organism, but the result of its fermentative action upon particular 
materials. 

It is, however, to be added that in the course of the next month a deposit 
occurred upon the sides of both these glasses such as I never saw under any 
other circumstances, constituting a film which, in the artificial milk, resembled 
coagulated fibrine in its toughness, and in the Pasteur’s solution was tenacious 
though not viscid, as if the motionless bacteria which constituted the deposit 
in each case had been glued together by a minute quantity of some intervening 
substance. 

The next observation which I have to record has reference to the origin 
of bacteria. It will be remembered that a filamentous fungus made its appear- 
ance on the interior of the first milk-glass six days after its exposure. The 
growth continued to spread, and by the tenth day, as it had a bloom indicating 
probable fructification, I scraped off a small portion from the glass by means of a 
tenotomy knife washed with strong carbolic solution and dried in the flame, 
and examined the specimen in a drop of water with the microscope. It proved 
to be a fungus of great beauty composed of very delicate branching filaments 
(a, Plate XI), bearing spores (conidia) often septate, characterized by a raw 
sienna tint (c, Plate XI) which was often distinctly seen to be confined to an 
external envelope, affording, what is unusual with fungi of such minuteness, the 
means of definite recognition, and of ascertaining with precision the three modes. 
of germination above alluded to (see pp. 302, 309). Many of the spores were 
seen to have produced thick sprouts to form young plants. Of these d has been 
sketched because it happened that, while part of the brown envelope had been 
consumed in the process of germination, a portion still remained for identifica- 
tion. Other spores were observed in toruloid pullulation, as is seen at e in 
a mass still connected with the parent filament, and at g in a free and septate 
spore, while 7 was either a spore multiplying by pullulation, or a young plant 
of a brown colour. For here and there young plants were seen like 0 retaining 
the brown investment of the spores; and hence, as a dark-coloured coat of 
threads and spores is the special character of the order Dematiei among hypho- 


GERM THEORY OF FERMENTATIVE CHANGES vent 


mycetous fungi, and as de Bary has given the name Dematium fullulans to 
a closely allied microscopic fungus,’ I have ventured to suggest for this species 
the name Dematium fuscisporum. Further, the spores were often seen to give off 
exquisitely delicate threads as at 2 and k, while in / we have a combination 
of this delicate sprouting with toruloid pullulation in the same spore. Finally, 
there were observed in abundance among the filaments free bodies like / exactly 
resembling in form, size, and refractive power portions of these delicate sprouts. 
Some of them, not sketched, were seen to be branched, and yet, though in this 
respect and in the absence of the double rod-like character they deviated from 
the most typical form of bacteria, their bacteric nature was rendered indubitable 
by characteristic movement observed in several instances. I may add that in 
k that which is sketched as a branch of the delicate sprout was seen to oscillate 
from the position indicated to that of the dotted line, as if about to detach 
itself ; though this is an observation to which I do not wish to attach much 
importance, as the same appearance might possibly result from an accidental 
adhesion of a previously free bacterium. Taking the observation as a whole it 
affords proof positive of three distinct modes of germination of the spores of 
one and the same fungus, while there seems little reasonable doubt that the 
third mode was the source of the bacteria. 

It will be remarked that the bacterium which grew thus abundantly among 
the filaments of the Dematium on the dry glass differs entirely in appearance 
from that which was found in the milk and produced (as I think we are justified 
in saying) the viscous fermentation. And there is reason to think that they 
were in reality two entirely different species, and that the one derived, as it 
appears, from the Dematium (or some other exactly like it morphologically) 
which I have indicated in the plate as Bacterium No. II, existed in the milk 
along with that of the viscous fermentation (Bacterium No. I), though the 
latter took the precedence in development, so that the former escaped notice 
in the first instance ; as so commonly happens when germs of different kinds are 
introduced together into the same medium. For having inoculated a glass of fresh 
urine on the 30th of July with a portion of the viscid material from the second 
milk-glass, the product which first showed itself five days later by dimness of 
the liquid had none of the characters of Bacterium No. I, but resembled in 
elongated and curved form as well as in dimensions the one derived from the 
Dematium, see Plate XI, Urine, August 4. It was of course conceivable that 
the appearances in question might be merely the result of a modification of 
Bacterium No. I by the new medium in which it grew; the other alternative 
being that two bacteria had existed together in the milk, but that Bacterium 


1 See Morphologie und Physiologie dey Pilze, &c. Won Dr, A. de Bary, Leipzig, 1866, p. 183. 
LISTER I es 


322 A FURTHER CONTRIBUTION TO THE 


No. I was either incapable of growing in urine or had lost its vitality during 
the five weeks which had elapsed since its introduction, while Bactertum No. II 
had survived. The last appears to have been the fact; for on inoculating 
milk and Pasteur’s solution with the new bacterium, while it throve in both 
it retained the characters that it had in the urine and occasioned no viscidity 
of the milk. And further, when introduced into artificial milk, in which Bac- 
terium No. I grew so rapidly, Bacterium No. IT failed to grow at all, the fluid 
remaining unchanged for the twenty-six days during which it was kept under 
observation. 

Some other points were observed regarding Bactertum No. II which appear 
of sufficient interest to be placed on record. When first seen in the urine it 
was unbranched, and exhibited rotatory movements ; but when again observed 
two days later it was found of larger size, and often distinctly branched, see 
Plate XI, Urine, August 6, and entirely destitute of motion. On this day 
a minute drop of the urine containing the organism in this condition was intro- 
duced into a glass of turnip infusion decanted from a stock of that liquid which 
was prepared onthe 24th of February,and had then furnished the supply for twelve 
experimental glasses, but which retained its original characters as regards aspect, 
fresh odour, and faintly acid reaction, while the microscope revealed no organ- 
isms. After two days bacteria made their appearance of the characters shown in 
Plate XI, August 8, resembling those first seen in the urine in being unbranched, 
and even more active than they, with wriggling onward movement. Two days 
later the bacteria were again motionless and of larger size, and often manifestly 
branched, see Plate XI, August 10, the turnip infusion having now acquired 
a smell like that of strong turnip soup. Again four days later, the glass shade 
having lost all smell, I supposed the fermentation to be over ; but on examining 
a drop I was surprised to find that bacteria were present in abundance, but that 
all the large and branched ones had disappeared, and in their place was a progeny 
more minute than any seen before, showing sometimes the double rod form 
most characteristic of bacteria, see Plate XI, August 14, and exhibiting active 
movements of rotation and wriggling. The only explanation that suggested 
itself to my mind was that some material of limited amount in the turnip infusion 
yielded under the fermenting influence of the bacteria a volatile product (the 
same, perhaps, that caused the soupy smell) which, while it remained, exercised 
a modifying influence upon the organism, resulting in the branched and motionless 
variety, but on escaping, as indicated by the odourless state of the fluid, left 
the bacteria to return to their former shape and active movements. And this 
view was confirmed by the result of inoculating a second glass of the turnip 
infusion from the first on the 14th of August, when the bacterium had the minute 


GERM THEORY OF FERMENTATIVE CHANGES 323 


and active state for the second time. For precisely the same series of changes of 
the organism was then repeated, as is sufficiently shown by the sketches, Plate XI, 
August 15, 18, and 20. I dwell upon these circumstances because they afford 
an example of modification of bacteria under different conditions of the same 
medium, and also an instance of branching, which has been spoken of by Cohn 
in his recent work as something altogether foreign to this class of organisms.! 
I also venture to hope that facts like these will tend to give the reader addi- 
tional confidence in the trustworthiness of the mode of investigation. 

One other circumstance with regard to Bacterium No. II seems deserving 
of mention. As already stated, when introduced into a glass of boiled milk, 
it grew rapidly, having after three days the appearances shown in Plate XI, Milk, 
August 18, with active movement. There was, however, up to this time no 
change in the aspect, odour, or reaction of the milk. But in the course of a few 
days the upper part of the liquid assumed a peculiar golden-yellow tint, and 
a fortnight after inoculation the appearance was almost as if the yolk of a ban- 
tam’s egg were floating on the surface, while there was also some similar yellow 
material deposited at the bottom of the glass, and the main body of the milk 
had assumed a cream colour. The reaction was now distinctly though not 
strongly acid, but the glass shade had no sour smell, a very faintly urinous 
odour being the only one perceptible. The main body of the milk was a very 
soft coagulum, but the upper part was a thin, transparent liquid, the bright 
yellow material being deposited at the junction of the two. On examining 
a portion of the yellow substance with the microscope, I could discover nothing 
but a mass of motionless but unbranched bacteria such as are shown in Plate XI, 
September 1, and I could only conclude that the bacteria were themselves 
of yellow tint though too minute to show it under the microscope Yet it is 
a curious circumstance that the same bacterium in Pasteur’s solution had not 
this colour, but produced a pale pink tint by the deposit which it formed at 
the bottom of the glass. At this period I was obliged to suspend my observa- 
tions, but from what had been seen in the last few days it appeared that the 
bacteria were converting the coagulum into a transparent liquid, for the upper 
translucent layer was daily increasing in thickness. On looking at this time 
at the second milk-glass, in which the viscous fermentation had occurred at an 
earlier period, I found that the viscid upper part had changed to a similar golden- 
yellow colour, and under the microscope I found that Bactertum No. I had 
disappeared, and given place to Bacterium No. II. This yellow colour in milk 
I never saw caused by any other organism. 

‘The last observations which I have now to relate refer to the commonest 


FO Clit. 5b 136. 


Y 32 


324 A FURTHER CONTRIBUTION TO THE 


of all the fermentative changes to which milk is liable, that which results in the 
rapid evolution of lactic acid, and consequent precipitation of the caseine in the 
form of curd, a change which was attributed by Pasteur, so early as 1857, to 
the operation of a special organism! The frequency of this change in milk 
does not, however, appear to depend on specially extensive dissemination of 
the ferment, but rather upon the circumstance that the organism which we are 
about to study, when it does gain access to milk, takes the precedence of others 
in development, and that dairies being places in which this particular ferment 
abounds, the milk supplied from them is sure to contain it, as they are at present 
managed. For it is a remarkable fact, and one well worthy of the consideration 
of the dairyman, that while milk supplied for domestic use will turn sour in 
summer weather within twenty-four hours, yet of all the many instances in which 
I have observed alterations in milk caused by organisms introduced through 
atmospheric exposure, in no single case did the true lactic-acid fermentation 
occur. Some organisms have given rise to a primary alkaline alteration, strong 
or feeble, some have been neutral in their effects, while others have produced 
an acid condition indeed, but only feeble and slowly developed. 

It seemed worth while before closing this investigation, in which fermenta- 
tive changes in milk had occupied a prominent position, to apply our method 
of inquiry to the most frequent and therefore the most interesting of them all. 
Accordingly on the 14th of last month, August, I obtained from a dairy near 
Edinburgh, pervaded with the usual sour smell, about a pint of milk said to 
have been taken from the cow four hours previously and tasting perfectly fresh, 
the dairy woman bailing it out with a tin vessel from the pan in which it stood 
into a clean glass bottle which I had provided. One hour later about ten ounces 
were introduced into a flask purified by heat, and were subjected to the tem- 
perature of 212° Fahr. for three-quarters of an hour, the arrangements being such 
as have been fully described above, see p. 310, and on the following day four 
experimental glasses were charged each with about half an ounce of the milk 
by means of a permanent syphon (see above). The first milk that came from 
the syphon, received into another glass, had the taste of perfectly fresh boiled 
milk, it purpled both blue and red litmus paper, and exhibited under the micro- 
scope nothing but milk globules of all sizes including extreme minuteness. 
Meanwhile, the milk remaining in the bottle had undergone the usual change. 
At noon, twenty-three hours after it was taken from the cow, it tasted distinctly 
sour though still fluid, and sharply reddened blue litmus, and on microscopic 
examination motionless bacteria were seen in considerable numbers, of soft or 


* “Mémoire sur la Fermentation appelée Lactique,’ Annales de Chimie et de Physique, 3™° série, 
tome li, 1858. 


GERM THEORY OF FERMENTATIVE CHANGES 325 


delicate character, in pairs, fours, and chains (/eptothrix filaments) as repre- 
sented at ain Plate XII. The milk examined was in a wine-glass into which 
it had been poured from the bottle, and this was kept covered till 5 p.m. when 
a small drop was taken out for inoculation of one of the glasses which we may 
term Boiled Milk I. It was now more sour to the taste, and more sharply acid 
to litmus, and when diffused between plates of glass exhibited small white 
masses which the microscope showed to be granular (deposited caseine) while the 
motionless bacteria before observed were again seen in abundance. The glass 
also contained some larger portions of soft curd. Next day at 8.30 a.m., or 
fifteen and a half hours after inoculation, Boiled Milk I, though unaltered in 
appearance, had communicated a faintly sour smell to the air under the glass 
shade, while the smell of boiled milk was gone. A drop removed by pipette 
reddened litmus more than on the previous day, though still faintly blueing 
red paper, and under the microscope motionless bacteria were seen in consider- 
able numbers exactly similar to those observed in the unboiled milk, except 
that there was greater variety in their size, some being considerably larger, as 
shown in the plate at 6. At 5 p.m., twenty-four hours after inoculation, the 
glass shade gave a pleasant smell of slightly sour milk, and the reaction was 
sharply acid, but the milk was still fluid, and next morning rather more than 
thirty hours after inoculation the milk had set into a solid mass. 

On the same day (August 15) that Botled Milk I was inoculated as above 
mentioned, parallel experiments were made with turnip infusion and with 
urine, each of which received a minute drop from the same glass of sour milk. 
The turnip infusion was from the stock prepared in February, having both 
naked-eye and microscopic appearances unchanged ; and the urine was a glass 
prepared at the same time as that used for Bactertum No. II, retaining un- 
impaired in every respect the characters which it then had, seventeen days 
before. Neither of these glasses showed any signs of bacteric development on 
the 16th, the day after inoculation, but on the following day both were mani- 
festly nebulous, and both exhibited under the microscope numerous motionless 
bacteria. There was, however, a remarkable difference between the organisms 
in these two glasses. In the turnip infusion the bacteria did not differ very 
greatly from those in the boiled milk, except that the leptothrix form was very 
seldom seen, and that the segments of the pairs were sometimes of greater 
length, while unjointed specimens, also pretty long, made their appearance, 
as atc. In the urine on the other hand the deviations from the form in the 
milk were most remarkable, as will be sufficiently evident from an inspection 
of the plate under Urine I. Some indeed, like d, were not very different from 
the original leptothrix form, but even such specimens often exhibited, as that 


326 A FURTHER CONTRIBUTION TO THE 


one does, an elongated state of some of the segments of the chain, thus forming 
connecting links between the leptothrix and the widely different spirillum-like 
specimens such as e. Next day the same sort of appearances were again seen, 
and an observation made on the previous day was confirmed, viz. that vacuoles 
were present in the thicker specimens. This is well shown in the sketches 
g and h, in all of which there is also a further deviation from the type which 
has been lately held to be invariable in the entire group of bacteric organisms, 
and from whence the name schizomycetous, as applicable to a totally distinct 
order of fungi, has been derived, that is to say these bacteria, instead of multi- 
plving by transverse fission, are plainly increasing by pullulation, that is to say, 
by shooting out buds after the fashion of the yeast plant ; and it will be observed 
that these sprouts are by no means always in a line with the long axis of the 
organism from which they spring. Yet that they really were the same bac- 
terium was evident, not merely from transitional forms, but from specimens 
such as f/, in which in one and the same chain we have the leptothrix character 
combined with the long and thick vacuoled and pullulating organism. Similar 
observations were made on the following day ; and now even the smallest and 
most bacteriform specimens sometimes exhibited a minute vacuole, as is shown 
at 7. These appearances did not startle me as much as they would have done 
had I not seen something almost exactly similar in an earlier part of the 
investigation, though in another species of bacterium under totally different 
circumstances. 

Thinking it worth while to try how this organism would behave if trans- 
ferred from the urine to Pasteur’s solution, I used for that purpose some of 
the old February stock, still perfectly bright, inoculating on the 18th. Next 
day the fluid was distinctly nebulous as examined before a candle, and under 
the microscope I found motionless bacteria, not numerous, but obviously of 
new formation from the delicacy of their aspect, represented at k, in Plate XII, 
where they are seen to be of considerable thickness and length of the segments, 
which present a curious alternation of lightness and darkness in their substance. 
Though a pair and three are given in the sketch as well as a single one, solitary 
individuals were much the most frequent. Such was the appearance twelve 
hours after inoculation, but when twelve more hours had expired a very great 
change had taken place. Not only were the bacteria much more numerous, 
but very much smaller ; and instead of being commonly single, were invariably 
double, having in fact the ordinary appearance of minute bacteria (see Plate XII, 
/), and to complete the metamorphosis some of these bacteria were seen swimming 
actively in ordinary bacteric fashion. Two days later the liquid was consider- 
ably increased in opacity and I was struck with what I had never seen before 


GERM THEORY OF FERMENTATIVE CHANGES Bei 


in Pasteur’s solution, a sort of dirty or dingy appearance, as if a very small 
quantity of ink had been mingled with the liquid, and the deposit at the bottom 
of the glass, which was white on the previous day, had now the same dingy 
cast. Under the microscope the bacteria appeared much as on the last occasion, 
except that some were even more minute than any then were, so that it was 
impossible to say, except by their movements, that they were anything more 
than mere granules (see m, in Plate XII). At the same time active movement 
was more frequent than before. 

I now thought it well to ascertain whether these minute and active bacteria 
would reproduce in urine the same sort of organism as that which we could 
not but believe to have been their parents in that fluid. On this occasion, 
having no more of the fresh urine, I adapted a syphon to a flask which was 
prepared on the 1st of March, and had furnished the material for numerous ex- 
periments, yet retained its original brilliancy as well as odour unaltered, was 
distinctly acid to litmus, and displayed no organisms under the microscope. 
Twelve hours after the inoculation on the 21st the liquid was already manifestly 
nebulous, and on examination with the microscope bacteria were found, four or 
five in every field, differing from those that had been introduced in being very 
rarely double but long and large and often curved (vide Plate XIII, a), having thus 
returned to a considerable extent to the condition before seen in urine, but now 
differing from their former state in that fluid in frequently exhibiting character- 
istic though languid movements. After twelve hours more the previous con- 
dition in urine was still more closely approximated by greater length in the 
segments, as illustrated by 5, sketched because it happened to be at rest, though 
by no means having the longest unbroken segments that were observed. I now 
inoculated from this glass of urine another (Urine III) that had been decanted 
on the same day and had remained till then unchanged ; and twelve hours 
afterwards I sketched from this second glass the magnificent example of un- 
jointed spirilliform organism represented at #. At the same time languid move- 
ment was seen in many specimens. 

To complete the history of the behaviour of this organism in urine it may 
be added that, after the lapse of another fortnight, the bacteria in this glass 
were found again motionless and comparatively small, scarcely differing in 
appearance from those originally seen in the sour milk (vide foot of Plate XIII). 

With the view of determining precisely the identity of the minute organism 
in the Pasteur’s solution with the large one in urine, I stocked as follows, on 
the 21st of August, a ‘ glass garden’ consisting of a massive piece of plate-glass 
excavated by the lapidary into a broad and deep ditch around a central island, 
the ditch to serve asa reservoir of air. This glass, together with a thin covering 


328 A FURTHER CONTRIBUTION TO THE 


glass, had been exposed to a high temperature between metallic plates to diffuse 
the heat and avoid cracking, and cooled without access of dust. With heated 
forceps the covering glass was raised and, a minute drop of the Pasteur’s solution 
with its organism having been mingled with a large drop of urine on a glass 
plate purified by heat, a little of the mixture was placed on the island. The 
covering glass was then luted down with melted paraffin, applied with a hot 
steel pen after a drop of water, boiled and cooled under the protection of car- 
bolized cotton, had been placed in the ditch with the pipette to ensure a moist 
atmosphere. Immediately after this had been done I examined with the micro- 
scope and saw the minute bacteria of the Pasteur’s solution as shown at c, in 
the Plate, in active movement. On looking again five hours later I found 
those bacteria replaced by large ones as seen at d, still moving though the move- 
ment was now languid. Within this short time the one variety of the organism 
had been converted into the other. Even if we supposed that the thick ones 
were of a different kind and that one of them had been present originally in 
the garden unobserved by me, their large numbers at the end of five hours 
and the vanishing of the small ones would be equally inexplicable. Hence, 
I think, we may regard it as demonstrated that the minute bacteria of the 
Pasteur’s solution and the coarse ones of the urine were one and the same 
organism. 

Other more remarkable facts, however, remain to be recorded. On the morn- 
ing of the 22nd of August, wishing to ascertain whether this organism, after being 
so strangely modified in urine, in Pasteur’s solution, and then again in urine, 
retained the property of inducing the lactic-acid fermentation in milk, I intro- 
duced a minute drop of Urine No. II into a second glass of milk decanted at 
the same time as the former, and which we may designate Boiled Milk II. Nine 
hours later test-paper already indicated a slight degree of acidity, and bacteria 
were found, five or six in each field, about as thick as those in the urine of inocu- 
lation, and also pretty long, generally single, but sometimes double as shown 
ate, Plate XIII. On looking at the same slide four hours later I found that other 
bacteria, much more minute and showing active progressive or rotatory move- 
ments, were also to be seen, and next morning such minute and active ones 
were alone discernible in another drop taken for examination. The acid reaction 
was now more marked, and the acidity continued afterwards to increase, till 
within three days the milk had set into a solid mass. 

But along with the lactic-acid fermentation another and very different 
change took place in the milk during the first twenty-four hours. On first 
looking at the glass on the morning of the 23rd, twenty-one hours after inocu- 
lation, I was amazed to see at the bottom of the glass a deposit about a line in 


GERM THEORY OF FERMENTATIVE CHANGES 329 


apparent thickness as black as pitch, showing out in a glaring contrast to the 
white milk. The black material did not appear to undergo any increase in 
the course of the day or at any subsequent period. But there was a peculiar 
sickly, almost putrefactive, smell mingled with the sour odour of the air in the 
glass shade in the course of the next twenty-four hours, though this afterwards 
passed off, and by the time that curdling was complete a pure smell of sour 
milk was alone perceptible. On the 26th I turned out the curd to investigate 
the black substance. I found it adhering firmly to the bottom of the vessel 
so that it could be completely cleansed of the curd with a camel’s-hair brush 
without being detached ; and when I picked it out with a knife its lower surface 
had a brilliant polish, corresponding to that of the glass. It constituted a tough 
scale, between horny and leathery in consistence, and its upper surface presented 
numerous smooth round depressions with intervening ridges ; and it was plain 
that the pigment had been precipitated in the form of a heavy liquid, the particles 
of which had coalesced at the bottom of the vessel and afterwards solidified. 
The intensity of the colour was strikingly brought out by microscopic examina- 
tion under my highest power, when even parts of extreme tenuity, as at g, 
Plate XIII, distinctly showed the sepia tint of the mass. These very thin parts 
also afforded the opportunity of ascertaining that the substance was perfectly 
homogeneous and structureless. In other words, the dark substance was not 
a coloured organism, but a pigment formed from the milk as the result of the 
growth of an organism in it. The small amount of the material at my disposal 
permitted me to ascertain only that it was insoluble in water, spirit of wine, 
anhydrous ether, and a strong solution of caustic potash, both in the cold and 
boiling states of these fluids, and was also unaffected by cold nitric acid, but 
was dissolved by boiling nitric acid, to which it communicated a yellow colour. 
Heated in a glass tube with access of air it burnt without fusion, leaving a 
white ash. 

The question of course presents itself, what was the cause of this remark- 
able formation of pigment from the milk ? That it was induced by an organism 
introduced into the milk we cannot doubt. But was that organism the same 
bacterium that in the former glass of boiled milk, as in the original stock of 
unboiled milk, produced only the lactic-acid fermentation, but altered in function 
while modified in form by its residence in the other media, or was it some other 
species, some ‘ pigment bacterium’, to use Professor Cohn’s expression, coexist- 
ing with the lactic-acid ferment ? Before discussing this question I must direct 
attention again to the glassof Pasteur’s solution from which the second urine- 
glass was inoculated. It may be remembered that at the time of that inocu- 
lation there was already present a dingy or dirty aspect about that glass such 


330 A FURTHER CONTRIBUTION TO THE 


as I had never before seen in Pasteur’s solution. Next day this peculiar appear- 
ance was considerably increased, and on applying a pocket-lens, I discovered 
a number of minute dark brown specks disseminated over the glass, even close 
to the level of the liquid where the surface was vertical; each brown point 
having a tiny brown streak extending downwards from it. I succeeded in 
picking up one of these brown specks with the attenuated end of the pipette, 
and on examination found it made up of a mass of motionless bacteria of ordinary 
form, themselves colourless, but having sepia-coloured particles disseminated 
among them of the same tint and intensity of colour as the pigment from the 
milk, very irregular in form and varying in size from mere points, much smaller 
than the bacteria, to masses considerably larger, as is seen at u, Plate XII, 
showing that the pigment, though produced under the influence of the bacteria, 
as seems clearly indicated by its existing specially among the bacteric masses, 
yet was, as in the milk, a mere amorphous and unorganized product. Thus, 
we trace back the pigmentary function to the Pasteur’s solution, through the 
urine, although in the latter no pigment whatever was formed. This is in 
itself a point of interest, as indicating that the formation of pigment is not 
essential to the organism, but, just as in the case of the viscid substance pro- 
duced under the influence of Bactertum No. I, occurs only when the medium 
in which the bacterium is growing is of a nature fitted for furnishing the requisite 
materials. Further the knowledge that the organism which produced the 
pigment was present in the Pasteur’s solution and in the urine will aid us in 
considering the question whether that organism was or was not a different one 
from the lactic-acid ferment, and this we may now proceed to discuss. 

Supposing it to have been a separate organism, it is not at all likely that 
it found its way by accident into the first urine-glass or the Pasteur’s solution 
during the brief periods of exposure for inoculation or withdrawal of fluid for 
examination. For in no single instance have I known bacteria introduced 
before in this way. Nor can it have existed diffused through the original supply 
of milk, seeing that no pigment was produced in that stock or in the glass 
Boiled Milk No. I inoculated directly from it. We can only imagine it intro- 
duced from the original supply by supposing that it had entered the unboiled 
milk immediately before the inoculation of the first urine-glass, and was all 
taken up in the drop used for the purpose ; a contingency possible but not 
probable. 

3ut even if we admitted that, in spite of the slenderness of the chance of 
such an occurrence, a separate ‘ pigment bacterium’ had made its way acci- 
dentally into the first urine-glass or that of Pasteur’s solution, we should find 
ourselves confronted by a further series of improbabilities. We should have 


GERM THEORY OF FERMENTATIVE CHANGES 331 


to suppose that the two bacteria thus coexisting in the two fluids were both 
modified in form in the same manner by the two media, both becoming coarse 
and long-segmented in urine, and both minute and of ordinary bacteric aspect 
in the Pasteur’s solution ; for none of the minuter kind were seen in the former 
fluid, nor any of the coarser sort in the latter. Further, we should have to 
suppose that the ‘ pigment bacterium’, when introduced into milk, grew with 
ereat activity for twenty-four hours and then suddenly perished. For we have 
seen that no further deposit of pigment took place after the first night, although 
the milk remained fluid considerably longer, and on microscopic examination 
of a drop from the upper part of the glass next day, when granular masses of 
caseine showed that coagulation had begun, I discovered not a vestige of pigment 
in it. And in further proof that the pigment bacterium, supposing such a 
separate organism to have been present, had died, I found that a bit of the curd 
introduced from this glass at the close of the third day into another glass of 
the same boiled milk, gave rise to the lactic-acid fermentation, pure and simple, 
with no formation of pigment, and none of the putrid odour that had attended 
the pigmentary formation in the other glass. It may, perhaps, be suggested 
that the ‘pigment bacterium’ was poisoned thus early by the lactic acid 
generated under the influence of the other (supposed) organism. But unfor- 
tunately for such a view, we find the same transient character of the pigmentary 
function in urine asin milk. For, as has been before mentioned, the day after the 
inoculation of Botled Milk No. II from Urine ITI (resulting in the pigmentary 
fermentation), I introduced a drop from Urine IJ into another glass of the same 
urine with the result of reproducing in great beauty the long unjointed form 
of the bacterium. After two days more I inoculated from this Urine No. III 
a fourth glass of the boiled milk, in the hope of getting back the pigmentary 
formation. But no such thing occurred, merely the lactic-acid fermentation. 
Now it is scarcely conceivable that the ‘ pigment bacterium’ (supposing it 
present) should have perished so quickly in the urine as well as in the milk. 
For it is to be remarked that the urine was but little changed by the bacteric 
development that followed the inoculation, retaining its acidity at the close 
of the two days, while little effect was produced upon its odour. Besides this 
it must be borne in mind that, if the supposed ‘ pigment bacterium’ was derived 
from the original stock of sour milk, it had before survived a residence for three 
days in urine, which was the fluid originally inoculated. 

On the other hand, if we admit that there was only one organism present, 
but modified in function as in form by the different media, the course of events 
is exactly what we might have anticipated. It was in the Pasteur’s solution 
that the pigmentary function first manifested itself, not indeed during the first 


332 A FURTHER CONTRIBUTION TO THE 


thirty-six hours, during which it is distinctly recorded that the deposit in the 
glass was white, but in the course of the next day ; and it is natural to suppose 
that it was in this medium, in which the form became so greatly modified, and 
at the same time the function of active motion conferred upon the previously 
motionless organism, that the faculty of pigmentary fermentation was also 
acquired. Then, just as modifications of form assumed by a bacterium in any 
one medium are more or less quickly lost when the organism is restored to its 
previous habitat, so should we expect it to be with altered function, and this 
bacterium, when transferred from the Pasteur’s solution to either milk or urine, 
would more or less quickly lose the new fermentative property which it had 
acquired. 

One clear instance of acquisition of a new function by the bacterium is 
presented by the power of active movement which showed itself for the first 
time in the Pasteur’s solution ; so that if we were to adopt the language of some 
authors who have attributed a most exaggerated importance to movement as a 
distinctive character, we should say that the organism was converted in that fluid 
from a bacteridium to a bacterium. But when restored to urine, the organism 
moved but languidly, and after about two days became again motionless. In 
milk, on the other hand, the power of motion was more permanently retained, 
and active movements were observed both in the third and the fourth glass 
of boiled milk as late as five days after the organism had left Pasteur’s solution. 

There is another consideration which seems strongly confirmatory of the 
argument against a distinct ‘ pigment bacterium’ as the cause of the black 
deposit in the milk. If it were true that such an organism existed, which, 
when introduced along with the lactic-acid ferment, would produce this striking 
effect, black milk would be a thing of frequent occurrence ; whereas this is, 
so far as I am aware, the first time such a thing was ever seen. But if it be 
asked, Why was it that this unheard of appearance showed itself in my experi- 
ment ? the answer is that the conditions of the experiment were such as to 
afford the organism opportunities which it had probably never had before. 
Never before, in all probability, was this organism allowed to develop unmixed 
with any other in urine and Pasteur’s solution consecutively. For while this 
ferment takes the precedence of others in milk, such is far from being the case 
in urine, and very probably in Pasteur’s solution also. How far the previous 
residence in urine may have predisposed this bacterium to assume the pig- 
mentary fermentation in Pasteur’s solution, further experiment can alone decide. 
Suffice it to say, meanwhile, that the conditions under which the organism 
grew were novel, and therefore novel appearances need not surprise us. The 
case seems exactly parallel to that of Bacterium No. I. Never before, perhaps, 


GERM THEORY OF FERMENTATIVE CHANGES 333 


was milk converted into so viscid a material as it was under the influence of 
that organism, simply because other organisms which would have interfered 
with the viscous fermentation were for the first time excluded. 

I have dwelt at what will, I fear, be thought tedious length upon this dis- 
cussion, because the conclusion arrived at seems to me of extreme importance. 
For if the same bacterium may, as a result of varied circumstances, produce 
in one and the same medium fermentative changes differing so widely from 
each other as the formation of lactic acid and that of black pigment in milk, 
it becomes readily conceivable that the same organism which under ordinary 
circumstances may be comparatively harmless, may at other times generate 
products poisonous to the human economy. We can understand, for instance, 
a thing that has at an earlier period of my practice as a surgeon often puzzled 
me, though now, happily, under the antiseptic system of treatment, I never 
have occasion to witness it, viz. the development of hospital gangrene beneath 
dressings left for a long time unchanged, whereas in the same hospital ward 
sores dressed daily continued healthy. Assuming what analogy leads us to 
suspect, that some organism is the cause of the disease, why should the special 
virus of hospital gangrene become introduced into a sore under the former 
condition more than under the latter? We now see that it is not essential to 
assume the existence of a special virus at all, but that organisms common to all 
the sores in the ward may, for aught we know, assume specific properties in 
the discharges long putrefying under the dressings. Similarly, we can imagine 
the unhealthiness of an old uncleansed hospital as caused not by the intro- 
duction into it of new organisms, but by a modification of those common to it 
and to freshly built institutions. I take these illustrations from surgery ; but 
to the medical reader others of equal importance will readily suggest themselves 
from physic. 

Another peculiarity of the glass of Pasteur’s solution remains to be men- 
tioned besides the formation of pigment in it, viz. a putrid smell which I never 
observed before in that fluid, and at the same time, a remarkable taste, a com- 
bination of slight bitterness with astringency, the latter so marked as to lead 
me to test for gallic or tannic acid with a persalt of iron, though without effect. 

Admitting then that we had here to deal with only one bacterium, it pre- 
sents such peculiarities both morphologically and physiologically as to justify 
us, I think, in regarding it as a definite and recognisable species for which I 
venture to suggest the name Bacterium lactis. This I do with diffidence, believ- 
ing that up to this time no bacterium has been defined by reliable characters. 
Whether this is the only bacterium that can occasion the lactic-acid fermenta- 
tion, I am not prepared to say ; but it seems most unlikely that any other kind 


- 


334 GERM THEORY OF FERMENTATIVE CHANGES 


will be found combining all the peculiarities of that which we’ have studied. 
What fungus it is derived from, if, indeed, it have come from any (for it would’ 
be rash to assume that such an origin is universal), I have no means at present 
of knowing ; but, however that may be, it cannot but be right, where we have. , 
definite characters of bacteria, to speak of them as species as a matter of con- 
venience, just as is done of various hyphomycetous jute known to be only 

inferior varieties of ascomycetous forms. : 

What are the functions of bacteria with reference to ‘itis physiology af fungi, 
and whether a bacterium derived from a fungus is ever capable of returning 
to the form of its parent, are questions on which my investigation has thrown 
no light. 

The sketches which furnished the illustrations were all drawn on the scale 
given at the foot of Plate XIII, either by camera lucida or, in a few cases where 
the objects were in motion, by eye-piece micrometer, the magnifying power 
being 1,140 diameters. The object-glass which I employed was a tenth immer- 
sion lens manufactured by Messes. R. and J. Beck, the beautiful definition of 
which was distinctly enhanced by the use of the higher eye-piece. 


Plate XI 
Dematim  Fasctsporun. 


In Mith I. | In Artificial Mith. | In Mitk I. 
eas ae esos area 
mm 6 & vor re ~ 0 Pyke 
& cd 2 Ro0° 
Bacteriusny N° #1. 
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: y f om 
at Nee 4 
actwe 
_ Be Ang 
a7 = 
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ist Sept. 
Lr Pasteurs Solution 
Ny Sere) A ee 
. ira, ' ( ' > 
active 
20 Aug. 
motionless 
on 28” Aug. 


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UOrsnpUy dry uy 


YEN 4205 2 


ON THE NATURE OF FERMENTATION 


The Introductory Address delivered-in King’s College, London, at the Opening of the Session 
October'1, 1877. 


[Quarterly Journal of Microscopical Science, April 1878.] 


GENTLEMEN.—In making my first appearance as a teacher in King’s College, 
I cannot refrain from expressing my deep sense of the honour conferred upon 
me by the invitation to occupy the chair which I now hold; and, at the same 
time, my earnest hope that the confidence thus reposed in me may not prove 
to have been misplaced. | 

In considering how I could best discharge my duty as the person selected 
to deliver the Introductory Address of the Medical Session, I have felt that 
two courses were open to me: either to spend the short but important time 
at my disposal in an endeavour to convey to the student some sense of the 
exalted privileges, and correspondingly high responsibilities, of the beneficent 
calling to which he proposes to devote himself, or to treat on some special subject, 
in the hope that I might say something which should have interest, and, if 
possible, even instruction, not only for the student, but also for the eminent 
men whom I have the honour to see around me. The latter is the course which 
I have decided to follow, and the subject which I have selected is a short account 
of an inquiry in which I have been engaged in the interval between the cessation 
of my official duties in Edinburgh and their commencement here. The object 
of that investigation was to obtain, if possible, some more precise and definite 
knowledge of the essential nature of a class of phenomena which interest alike 
the physician, the surgeon, and the accoucheur. I allude to the changes in 
organic substances which are designated by the general term fermentation. 

In medicine, the large class of diseases termed zymotic derive their name 
from the hypothesis that their essential nature is fermentative. In obstetrics, 
puerperal fever, the most frequent cause of disaster after childbirth, is now 
regarded by many of the highest authorities as likewise due to fermentative 
disorder ; and, in surgery, among the various causes which may disturb a wound, 
we know that by far the most frequent in operation, and the most pernicious 
in its effects, both upon the wounded part and upon the constitution, is putre- 
factive fermentation. If this be so, it is clear that to understand the nature 
of fermentation must be a matter of the very highest importance, with a view 
to curing or preventing the various evils to which I have alluded. 

What, then, do we mean by fermentation? I shall best approach the 
answer to this question by giving an example. Rather more than a week ago, 


336 ON THE NATURE OF FERMENTATION 


I witnessed in the north of Italy the time-honoured practice of treading grapes 
in the wine-vat. I was told that the juice would within twenty-four hours 
boil, as it was said, over the vats into which it was introduced ; in other words, 
that the sugar of the grape-juice would within that short time be so converted 
into alcohol and carbonic acid that the carbonic-acid gas, by its evolution, 
would cause sufficient frothing to produce the effect to which I have referred. 
This conversion of the sugar of the grape into alcohol and carbonic acid is 
accompanied by the development of a microscopic organism, the yeast plant, or, 
to continue the old nomenclature, Torula Cerevisiae, consisting of microscopic cells 
multiplying by pullulation, as indicated in this diagram (not here represented) 
Now, it is, I believe, universally admitted that the alcoholic fermentation o 
grape-sugar is due to the growth of the yeast plant. M. Pasteur thinks that 
he has traced the origin of the yeast plant in the juice of the grape to a minute 
fungus adhering to the outside of the skin of the grape.t. Be this as it may, 
it is admitted on all hands that the alcoholic fermentation is caused by the 
growth of the yeast plant. So long as the juice of the grape is protected by the 
skin of the berry, no fermentation occurs ; but, as soon as it escapes from that 
protection, the organism, by its development, induces the fermentation. Nor is 
it by any means exclusively in the natural juices of fruits that such fermentation 
occurs. Any sugary solution, provided it contains, besides the sugar, other 
ingredients requisite for the nutrition of the yeast plant, will serve as pabulum 
for the organism, and in that case the yeast plant will give rise to the fermenta- 
tion. Here is a glass containing such a liquid, termed Pasteur’s solution, because 
it was devised by M. Pasteur for the very purpose of affording nourishment to the 
yeast plant and other minute organisms. This was prepared on the 7th of August 
in a flask purified by heat, covered over with a cap of pure cotton-wool,? which 
allows the entrance of air, but does not permit the access either of the yeast 
plant or of any other form of dust. The Pasteur’s solution, containing, besides 
sugar, ammoniacal and earthy salts for the nutrition of the fungus, was heated 
to about the temperature of boiling water, so as to destroy any organisms that 
might exist in the water. The result is, that it continues perfectly unchanged, 
just as it was on the 7th of August; but, if we were to add to it a little of the 
yeast plant from fermenting grape-juice, we should find that, at the temperature 
of summer weather, it would very soon be in a state of free fermentation at 
the same time that the yeast plant would multiply. This, then, is a typical 
instance of fermentation. We have an active agent termed the ferment, which 


1 Vide Pasteur, Etudes sur la Biére, pp. 150 sqq. 

* The cotton-wool was rendered free from living organisms by soaking it with a solution of carbolic 
acid in one hundred parts of anhydrous ether and allowing the ether to evaporate, leaving the carbolic 
acid behind in the cotton. 


—_—_ 


. 
: 
‘ 


ON THE NATURE OF FERMENTATION 337 


ferment is capable of self-multiplication. That I believe to be the essential 
property of a true fermentation. Now, in this particular case, I have already 
said it is admitted on all hands that the yeast plant is the cause of fermentation. 
Persons may differ as to how the development of the yeast plant gives rise to 
the resolution of the sugar into the alcohol and carbonic-acid gas ; but all now 
agree that, somehow or other, the organism causes the fermentation. Now, 
is it the case that all true fermentations are caused by the development of organ- 
isms? That, gentlemen, is the question which it is desirable that we should be 
able to answer. 

Take, for example, the case of the putrefactive fermentation of blood. We 
all know that, if blood be shed from the body into any vessel without special 
precautions, in a few days it putrefies. The bland nutrient liquid, soon after 
leaving its natural receptacle, becomes foul, acrid, and poisonous; a change 
fully as striking as that which grape-juice undergoes in the alcoholic fermenta- 
tion. Here, on the other hand, we have a vessel (a liqueur-glass) into which 
blood was received with special precautions. In the first place, the glass, covered, 
as you see, with a glass cap and a glass shade, with a view of preventing the 
access of dust, and standing upon a piece of plate-glass, had been heated to about 
the temperature of 300° Fahr., and cooled with an arrangement which ensured 
that the air which entered during cooling was filtered of its dust ; so that we 
were perfectly sure that the glass contained at the outset no living organisms. 

Then, in the second place, the glass had been charged from a flask like this, 
provided with a spout. It contains, as you see, a glass tube introduced into it ; 
it is stuffed well with cotton-wool between the neck of the flask and the tube, 
there 1s a piece of cotton-wool over the end of the tube, and another piece is 
tied securely over the spout of the flask. The flask so arranged was heated 
just as the glass had been heated. It is not necessary to have the temperature 
so high as to singe the cotton. Heat far short of this is adequate, according 
to my experience, to make perfectly sure that you destroy all living organisms. 
The flask having been thus prepared, the jugular vein of an ox was exposed and 
divided, with precautions against the entrance of anything putrefactive,' and, 
the cotton cap having been taken off from the end of the tube, the vein was 
slipped over the tube and securely tied on, and then the hand of the assistant, 
who previously restrained the flow of blood, being relaxed, blood was permitted 
to flow into the flask. Then, before coagulation had time to take place, this 
and various other similar glasses were charged after the removal of the cotton 
cap from the end of the spout. Now, the first thing that may strike you is the 


' This was secured by washing the skin and the instruments with a strong solution of carbolic acid 
(1 to 20), and performing the operation under a carbolic spray. 
LISTER I Z 


338 ON THE NATURE OF FERMENTATION 


remarkable fact that this blood-clot has not undergone any contraction. One 
of the earliest things that your professor of physiology will have to teach the 
junior students will be that blood, after coagulation, contracts ; that the fibrine 
of the coagulum shrinks and the serum is pressed out. But here no such thing 
has taken place. There has been no shrinking of this clot, no pressing out of 
the serum, and I venture to say that there is no one here—at least I think it is 
unlikely that there is any one here except myself—who has seen such a pheno- 
menon, illustrating how, when the most familiar objects are placed under new 
circumstances, the most unexpected results may arise. Now, this is a matter 
of very considerable interest with reference to the behaviour of blood-clots 
inside the body in wounds and so forth. However, that is not a point on which 
I wish to dwell on the present occasion.t The point to which I wish to draw 
your special attention is, that this blood, although it has been six weeks in this 
glass, without any close fitting of the glass shade or the glass cap, and therefore 
with free opportunity for the access of the gases of the atmosphere, has not 
putrefied. The air in the glass shade is perfectly sweet, perfectly free from 
odour. 

Now, gentlemen, this, without going further, is a very important matter. 
It proves that the blood has no inherent tendency to putrefaction. It further 
proves that the oxygen of the air is not able to cause the blood to putrefy, as 
used to be supposed. There was a time—the effect is still seen to a certain 
extent—when the dark venous colour of this blood-clot gave place to the crimson 
colour of arterial blood in a gradually deepening band from above downwards. 
We still see some of the red colour remaining, though now the converse effect 
has begun to take place. That florid redness, gentlemen, showed that the 
oxygen of the air was in reality acting upon the blood, yet it did not putrefy. 
Now, if I were to take a little morsel of already putrefied blood, say, upon the 
end of a needle, and touch with it this clot of blood, putrefaction would, in the 
course of a very short time, spread throughout the mass. Exactly as in the 
case of alcoholic fermentation under the influence of the yeast plant would the 
fermentation spread. 

Putrefaction, then, is a fermentation, a true fermentation, characterized 
by the power of self-multiplication of the ferment. Then, gentlemen, if we 
examine microscopically, we find in the putrefying blood, as we found in the 
fermenting grape-juice, microscopic organisms, termed bacteria from their rod- 
shape, which we have represented in this diagram on the same scale as we 
had the yeast plant ; of different sizes, but all very much more minute than 


* I desire to guard myself against being supposed to express any opinion here as to the cause of 
this phenomenon, 


ee 


Ti RE Bc ith tl lat Natta ci 


aN iad 


ON THE NATURE OF FERMENTATION 339 


the yeast plant, and commonly endowed with a remarkable power of locomotion. 
I say that, in the putrefying blood, we find these organisms developing pari 
passu with the fermentation. 

Now, the question is, Are these bacteria the cause of the putrefactive 
fermentation, or are they merely accidental concomitants ? These are two 
views which are entertained at the present day by men of high eminence. It 
may be said, ‘ Why should there be any doubt that the bacteria are the cause 
of the putrefactive fermentation, any more than there is a doubt that the Torula 
Cerevisiae is the cause of the alcoholic?’ Well, one reason I believe to be that 
the bacteria are so exceedingly small. They are not so easily defined as the 
yeast plant. We cannot get them in a mass as we can get a mass of yeast ; 
at least without a great deal of trouble ; and, besides that, they occur very 
similar in appearance in a great number of different fermentations. There is, 
therefore, so far some colour for doubting whether bacteria are the cause of 
a special fermentation, like this putrefaction. Then there is another ground 
justifying such a view; for certain it is that organic substances are lable to 
extremely remarkable alterations, decompositions, under the influence of agents 
which are endowed with no life at all. As good an example of this as we can 
take is what occurs in the bitter almond when it 1s bruised with water. You 
all know what takes place under those circumstances; that there is prussic 
acid developed, and essential oil of almonds, with other materials. Now, these 
did not exist beforehand in the almond, but they are the result of the mutual 
action upon each other of two constituents, neither of which was hydrocyanic 
acid nor oil of bitter almonds, &c. These two constituents are termed emulsin 
and amygdalin. Amygdalin can be got from the almond in the form of definite 
crystals ; and emulsin, though not a crystallizable substance, but a variety 
of albumen, can also be obtained separate. Till these two materials are in 
a state of solution in water, they do not act upon each other at all; but, as 
soon as they are in watery solution, the emulsin so acts upon the amygdalin 
that the latter becomes broken up into the constituents to which I have referred. 
This is an exceedingly remarkable fact. Undoubtedly, the emulsin is dead ; 
there is nothing living about it. It is not an organism. It is obtained by a 
process of alcoholic extraction, and so forth. It is thoroughly a chemical sub- 
stance, a merely dead substance, if we may so speak, and yet it does produce 
this remarkable effect upon the amygdalin. But, when we come to consider 
this case, we find that the process, remarkable as it is, lacks the true character 
of genuine fermentation, that of the faculty of self-propagation of the ferment. 
Liebig himself, who was the great advocate of the doctrine of so-called chemical! 


ferments, and who, along with Wohler, discovered this action of emulsin on 
Z2 


340 ON THE NATURE OF FERMENTATION 


amygdalin, pointed out, and showed by irrefragable evidence, that the emulsin 
does not undergo any multiplication ; not only so, but that, after a while, the 
emulsin loses the property of acting on the amygdalin: but, for a considerable 
time, it continues to act upon it without undergoing apparently either increase 
or diminution of its bulk. It may be called a resolvent, the amygdalin being 
the resolved material. 

There are other cases equally striking that might be mentioned, not only 
in the chemistry of vegetables, but in the chemistry of our own bodies. There 
exists, for instance, in the saliva a material called ptyalin, which has a remarkable 
power of acting upon starch, so as to convert it into soluble compounds. In the 
gastric juice there is a material called pepsin, which has an equally remarkable 
property of acting on albuminous materials, fitting them for solution in digestion. 
3ut here again we find, when we come to consider the matter, that there is no 
evidence whatever that either pepsin or ptyalin is capable of self-multiplication. 
Each is secreted for the purpose and in the quantity in which it is required, 
but it has no faculty of self-propagation ; and I believe, if you search through 
the whole range of organic chemistry, you will not find a single established 
instance where any ferment, so called, destitute of life has been proved to have 
the power of self-multiplication. At the same time, gentlemen, it may be 
admitted that the thing might be theoretically possible. It 1s conceivable, for 
instance, that a resolvent, if we may so speak, of comparatively simple con- 
stitution might, by its action upon a resolvable compound, resolve it into sub- 
stances, one of which should itself be the resolvent, and, if that were so, the 
process might go on ad infinitum. That is conceivable; and accordingly, 
although we have no instance of the kind on record, yet we have persons in 
high authority, as teachers both of physiology and of pathology, maintaining 
the view that in putrefactive fermentation, for instance, the bacteria are pro- 
bably mere accidental concomitants ; that the real essential agent in the putre- 
faction is not an organism at all, but some so-called chemical ferment destitute 
of life. Andso long as we have authorities maintaining such a view, it 1s neces- 
sary to test its truth or falsehood by searching inquiry ; and such has been 
the object with which my investigations of the last two months have been 
conducted. 

As regards the putrefactive fermentation, we have already evidence in 
the flask and in the glass that I have shown you (the flask also has no putre- 
factive odour emanating from it), that blood has in itself no inherent tendency 
to putrefy. It must receive something from without, and that something is 
not mere oxygen or any other atmospheric gas. I have now to point out to 
you that the addition of water is not of itself sufficient to induce this fermenta- 


ON THE NAFURE OF FERMENTATION 341 


tion. Blood and water constitute a mixture highly putrescible, very much 
more so than blood itself. But in this flask we have had mixed with water the 
contents of one of the liqueur-glasses of unputrefied blood like that before shown 
to you. The water, however, had been previously boiled, so as to kill any 
organisms in it; boiled and cooled under the protection of a cotton cap, and 
then, the cotton cap being raised, careful provisions (into which I must not 
enter) against the entrance of dust being taken, the clot was spooned into the 
water ; a fresh cotton cap, perfectly pure, was put on, and so we got, I believe 
for the first time, a permanent cold watery extract of blood, and here it retains 
the same brilliant clearness that it had in the first instance, more than a month 
ago. Mere water, therefore, is as inadequate to induce the putrefactive fer- 
mentation of blood as are the gases of the air. 

But the fermentation which I have been especially investigating has not 
been the putrefactive, but one which seemed to me more convenient for the 
purpose, the lactic fermentation, by means of which milk sours and curdles, 
through conversion of the sugar of milk into lactic acid. This is a curious 
instance of a chemical transformation. The composition, as regards the pro- 
portions of the three elements, carbon, hydrogen, and oxygen, remains identically 
the same ; but those of you who are chemists understand what I mean when 
I say the atomic weight of the lactic acid is one fourth of the atomic weight of 
the sugar of milk. Each atom of milk-sugar is resolved into four simpler atoms 
of lactic acid. Now, it may be naturally supposed, if you observe what happens 
in a portion of milk obtained from a dairy, that there is an inherent tendency 
in the milk to this souring and curdling. If you get milk from a dairy and keep 
it long enough, it is certain to turn sour and curdle: then, after a while, there 
comes a certain mould upon the surface, the Ordium lactis, which constitutes 
the sort of bloom there is upon a cream cheese ; then comes on, often simul- 
taneously with the growth of this mould, the butyric fermentation, in which 
butyric acid is produced ; and afterwards, if you keep the milk long enough, 
it will probably putrefy. When you see, time after time, specimens of milk, 
taken from various dairies, undergo this succession of alterations, you may be 
tempted to suppose that these were changes to which the milk was disposed 
from its own inherent properties as it comes from the cow’s udder. The late 
eminent Professor of Chemistry in this College, Professor Miller, in his excellent 
work on Chemistry, states that the ferment of the lactic-acid fermentation is 
the caseine of the milk. I am bound to say, however, in justice to Professor 
Miller, that he also adds that M. Pasteur has expressed his belief that there 
exists an organic living ferment which produces this fermentation ; but Professor 
Miller does not profess to decide between these two opinions. On the contrary, 


342 ON THE NATURE OF FERMENTATION 


his first statement, that the caseine is the ferment, might lead you to suppose 
that he is inclined to the former view.' If this were the case, as there is caseine 
always in the milk, there should always be the lactic-acid fermentation. But 
it was pointed out long ago by M. Pasteur that, if you examine any specimens 
of souring milk with the microscope, you find little organisms.2 These, when 
you come to look at them carefully, you see to be obviously of the nature of 
bacteria. Bacteria may either have the faculty of motion or they may not. 
This particular bacterium is a motionless bacterium, so far as I know; still it 
has the essential nature of a bacterium: a microscopic fungus, multiplied by 
fissiparous generation, the lines of segmentation being transverse to the longitu- 
dinal axis of the organism. I have ventured to give to this little organism the 
name Bacterium lactis; for, gentlemen, no doubt there are different kinds of 
bacteria. The circumstance that they are minute must not make us shut our 
eyes to this truth. You sometimes hear bacteria spoken of as if they were all 
alike. The fact that some do not move and others do, is one indication of 
a difference between them. Another indication of a difference is, that some 
bacteria will thrive in a medium in which others cannot live. For instance, 
the Bacterium lactis refuses to live at all, according to the more careful experi- 
ments I have been lately making, in Pasteur’s solution; the very fluid pro- 
vided by Pasteur for bacteria, torulae, and other fungi to live in, is a medium in 
which the Bacterium lactis refuses to grow at all; although many bacteria grow 
in it with rapidity. That is clear evidence that this is a different kind of bac- 
terium from those which both thrive and move in Pasteur’s solution. You will 
observe, also, it is somewhat peculiar in the form of the segments ; they are 
oval, and not so rod-shaped as bacteria generally. These you will always find 
in milk when it is souring. 

But, gentlemen, neither the souring of milk nor the organism which is 
found associated with that change is the result of any inherent tendency in the 
fluid. This is a flask of boiled milk prepared on the 27th of August, with the 
same arrangements for ensuring purity of the vessel and excluding dust that we 
had in the flask of Pasteur’s solution. It has not coagulated ; it has undergone 
none of the changes to which I have alluded. There has been no butyric fer- 
mentation, no Ozdium lactis has formed upon it, no putrefaction has occurred. 
This milk is as sweet as when it was first prepared ; and if you were to examine 
it with the microscope, you would find in it no organism of any kind. From 
this same flask, with precautions with which I will not detain you, I have charged 


* Vide Miller’s Elements of Chemistry, third edition, vol. iii. 
* Vide ‘ Mémoire sur le Fermentation appelée Lactique’, Annales de Chimie et de Physique, 3™¢ 
série, tome lii, 1858. 


ON THE NATURE OF FERMENTATION 343 


various purified liqueur-glasses. This one has been charged for more than 
four weeks, yet the milk remains fluid, you observe, although there is abundantly 
free access of air to it. The oxygen of the air and the caseine which still exist 
in the boiled milk have together been unable to bring about the lactic fermenta- 
tion. As regards boiled milk, this is sufficient evidence that the lactic fer- 
mentation is not something to which the liquid is spontaneously prone ; it 
requires something to be introduced into it from without. For you must not 
suppose that the boiling has rendered the milk incapable of souring. All that 
it requires is the introduction of the appropriate ferment. If you were to touch 
the edge of the milk in this glass with the point of a needle dipped in souring 
milk from a dairy, within two or three days the whole would be a sour clot, 
showing both the proneness of boiled milk to souring and also the genuine 
fermentative character of that change as indicated by the faculty of self- 
multiplication of the ferment. And on microscopic examination you would 
be sure to find the Bacterium lactis present throughout the mass. 

But though the ferment which occasions the souring of milk is present in 
the milk obtained from any dairy, it appears to be by no means common in the 
worldin general. Suppose you take a series of glasses of boiled milk like these, 
and introduce into them a series of drops of ordinary unboiled water, you will 
get fermentation in them. If you put into each, for instance, a drop as large 
as a quarter of a minim, you will have a fermentation in every one, and an 
organism in every one; but you will neither have, according to my experience, 
the lactic-acid fermentation nor the Bacterium lactis. You will have bacteria 
of other sorts ; fermentations of other kinds. Again, suppose you take a series 
of such glasses, take off the glass shades and the glass caps, in different apart- 
ments or at different times, and expose the milk to the air-dust for half an hour ; 
you will get fungi and bacteria of various sorts, but, according to my experience, 
you will not get the Bacterrum lactis; nor will you get the lactic fermentation. 
And thus it turns out, so far as boiled milk is concerned at all events, that the 
ferment that brings about this particular fermentation is a rare ferment. So 
far from boiled milk being spontaneously prone to the change, it requires some- 
thing to be introduced from without which is a rarity both in ordinary water 
and in ordinary air. 

But then, it may be urged, indeed such arguments have been used, this 
may be very true for boiled milk, but how about unboiled ? ‘ May it not be 
that, by boiling the milk, you have destroyed certain chemical ferments, purely 
hypothetical we must admit, but which we think likely to exist ?’ For, accord- 
ing to the views of some persons, it may be that in the unboiled milk there 
may exist certain chemical substances prone to evolve into organisms by spon- 


344 ON THE NATURE OF FERMENTATION 


taneous generation, and prone to produce these and other fermentations, but 
which, by the act of boiling, we deprive of this tendency. Therefore, with 
a view to meeting this objection, the first part of my investigation was devoted 
to endeavouring to see whether or not milk, as it comes from the cow, really 
does or does not contain materials tending to the development of organisms or 
to fermentation of any kind. 

An exceedingly simple experiment will probably serve to convince you to 
a considerable extent with regard to this matter. If you go to a dairy where 
there is also a cow-house, take a couple of clean bottles, and fill one with milk 
from a pan in the dairy and the other with milk direct from the cow in the cow- 
house, the milk obtained from the dairy will be certain to sour, but that which 
you get direct from the cow will very probably never sour at all. It will prob- 
ably acquire a nasty bitter taste, and will not contain the Bacterium lactis or 
the Ordium lactis, but some other kinds of fungi. That very simple experiment 
is enough to show that the lactic-acid fermentation is not a change to which 
unboiled milk is spontaneously prone. And it occurred to me that, if all organ- 
isms and fermentations which occur in milk really depended on accidental 
introduction from without, by performing the experiment with a number of 
purified glasses and taking the milk in small quantities into each, we might by 
thus subdividing elude the foreign element and get the milk, in some of the glasses 
at least, not only without the lactic-acid fermentation or the Bacterium lactis, 
but without any fermentation or any bacterium, or any sort of organism. 
Accordingly, I prepared little glasses like these ; little test-tubes with test-tube 
caps, arranged upon a stand made of pieces of glass tube and silver wire. The 
stand containing the test-tubes was placed under a glass shade on a plate of 
glass and purified by exposure to 300° Fahr. in the hot box. Miulk having been 
received from the cow into a purified vessel, some of the milk was then, by 
means of a syringe attached to this pipette (the pipette having been also pre- 
viously purified), drawn up into the pipette, and then, by means of the syringe, 
each little cap being in succession raised, a few minims of milk were introduced 
into each of the glasses, the caps being immediately reapplied. The result was, 
every one of the milks underwent fermentation, and every one of them con- 
tained organisms, some of them as many as three different species. The great 
majority of those twelve glasses presented little orange specks, such as were 
never seen, I suppose, in any milk before ; and, on examining these, I found 
them to be little organisms belonging to a group to which I have ventured to 
give the name Granuligera, because they consist of granules, different from 
bacteria in this respect, that you might suppose them not to be organisms at 
all till you had the opportunity of seeing them undergoing multiplication by 


ON THE NATURE OF FERMENTATION 345 


fissiparous development, in a manner, however, differing from the transverse 
fissiparous multiplication of bacteria, in being crucial.’ But, besides the granu- 
ligera, there were among the contents of these test-tubes bacteria of different 
kinds, to judge by form and size, and in one of them was a toruloid organism, 
and in two others two species of filamentous fungi, one of which was of the most 
exquisite delicacy, though in general type of the same sort of arrangement as 
the common blue mould or the Ozdium lactis. The size of the filaments was so 
exceedingly small that twenty of them would lie abreast in a single human red 
corpuscle ; they were smaller in diameter than even the Bacteriwm lactis, smaller 
than the great majority of bacteria. I doubt if any such exquisitely delicate 
filamentous fungus has ever been seen before even by a professed botanist like 
my colleague Professor Bentley. But there was no Bacterium lactis, and there 
was no lactic-acid fermentation. 

What inference were we to draw? Was I to suppose that, although the 
lactic-acid ferment had been excluded, it was impossible to exclude others ; 
that others were present in the milk as it existed in the cow’s udder ; or was it 
that I had not been sufficiently careful ? The latter was the view I was disposed 
to take. The experiment had been performed in the cow-house, where certainly 
the air might be supposed to be reeking with organisms. I therefore per- 
formed the experiment a second time, and this time in the open air. It must 
be confessed it was not far from the cow-house, and it was a fine day at the very 
time of the year in which organisms most abound. On this occasion, I used 
twenty-four of the little covered test-tubes ; those which you see before you. 
The result was that this time, again, every glass had organisms developed in 
the milk which it contained. At the same time, every glass seems to be different 
from all the rest. Such fermentations as there are here, I venture to say, were 
never seen in milk before. I have brought before you a diagram, showing some 
of them on a large scale. I want particularly to direct your attention to these 
strange scarlet spots which occurred in almost all of them. They began as tiny 
scarlet dots, which spread as fermentative changes capable of self-multiplication 
in the substance of the milk. Here is one glass that is green, and here is another 
of an orange-yellow colour. Here are two that have two kinds of filamentous 
fungi. I have not examined them microscopically, but I shall very likely find 
there are some species that have not been described. 

I felt little doubt that these organisms had got in for want of sufficient care 
on my part. But how are we to explain these unheard-of appearances ? Simply 
thus. If the Bacterium lactis had been here, it would have taken the precedence 
of all other organisms in its development, and the changes which it would have 


* Vide Tvansactions of the Royal Society of Edinburgh, vol. xxvii, p. 319 (page 281 of this volume). 


346 ON THE NATURE OF FERMENTATION 


induced would have made the milk an unfit soil for these other numerous species. 
And the novelty of the appearances depended not on the presence of an unusual 
variety of organisms, but merely on their having enjoyed an unprecedented 
opportunity for coming forward. Under ordinary circumstances they would 
have been smothered—killed—by the effects of the Bacterium lactis and the 
other ferments that commonly develop in its wake. Such being my belief, 
I determined to make one more attempt. This time I used again the original 
twelve glasses, but charged them with greater care. I mentioned that a large 
proportion of these glasses of the second experiment had scarlet spots; and 
in the former experiment in the cow-house the great majority had orange spots, 
and those, as we have seen, were composed of heaps of granules. It occurred 
to me that one cause of failure might be this. Suppose one single group of such 
granules to exist, and to become disturbed and broken up in the process of 
transference to the glasses, it might vitiate the whole specimen of milk; there- 
fore, instead of drawing up the milk into the pipette with a syringe and then 
expelling it, I determined to have it introduced as directly as possible into the 
little glasses. With this object I employed these two glass tubes, connected 
together, as you see, with a short piece of india-rubber tubing, the wider tube 
being for the purpose of receiving the milk, the narrower to conduct it into 
the glasses. The glass tubes had been purified by a high temperature, and the 
piece of india-rubber connecting them, as it would not bear a very high tem- 
perature, had been boiled for hali an hour. The same cow was taken out again 
into the open air, and this day the elements were in my favour. It had been 
a drizzly morning, and I might fairly hope that some of the multitudes of organ- 
isms existing in the little orchard might have been washed down and that the 
air might thus have been somewhat purified. I was also more careful in this 
respect. I got the dairywoman to milk the cow without drawing the hand 
over the teat, performing the operation by an action of the fingers in succession, 
so that the end of the teat should always be exposed. Her hands were washed 
with water, and the cow’s udder also, and she having squirted out a little milk 
to wash away any organisms from the orifice of the duct, the glass cap which 
protected the larger tube from dust was removed and the end of the tube was 
held in the immediate vicinity of the teat; a few drachms were introduced, 
then the cap was readjusted, and then these little glasses were filled by the 
simple expedient of alternately relaxing and compressing with the finger and 
thumb on the caoutchouc, so that there was as little disturbance as possible 
of the organisms that might be supposed to be introduced in spite of my care. 
It is six weeks since this was done. At first sight, you might suppose, con- 
trasting these appearances with those of the other tubes which were charged 


ON THE NATURE OF FERMENTATION 347 


only three days earlier, that the milks of this last experiment were all pure. 
The truth is, all but two have organisms in them ; but I may mention that all 
but four had obviously organisms in them before I went for my trip on the 
Continent three weeks ago. On my return I found that in the course of the 
three weeks that had elapsed, two others had gone ; Hut they already showed 
organisms which, though very pale and insignificant, were quite easily seen 
by a magnifier in such considerable mass that I felt sure they must have already 
been growing for a considerable time ; and, therefore, in all probability those 
that still seemed to the naked eye and to the magnifier free from organisms 
were really so. Accordingly, two days ago I drew out milk from one of those 
that seemed to be still pure, and I had the great satisfaction of finding it not 
only perfectly fluid and tasting perfectly sweet, with a perfectly normal 
reaction, purpling both blue litmus paper and red litmus paper—the normal 
reaction of perfectly fresh milk—but under the microscope I could not dis- 
cover any organism of any kind whatsoever. Therefore, I think we are 
justified in saying that in unboiled milk as in boiled milk, provided, of course, 
the cow be healthy, there does not exist any constituent having the power 
of giving rise to organisms or producing the lactic or any other fermentative 
change. 

This, gentlemen, was the first step of the investigation: to the second 
I must beg your special attention, because I believe you will agree with me 
that it is by far the more important step of the two. 

The object of the second part of the investigation was to find absolute 
evidence, if possible, whether the Bacterium lactis was or was not the cause 
of the lactic fermentation. It occurred to me that, 1f we could estimate with 
some degree of accuracy the number of bacteria present in a given quantity 
of souring milk, and then if we were to dilute the milk with a proportionate 
quantity of boiled water, we might have the diluted milk so arranged that every 
drop with which we should inoculate a series of glasses of boiled milk might 
contain, on the average, one bacterium ; and if we should do so, as it would be 
practically certain that the bacteria would not be distributed with absolute 
uniformity, we should expect that we might have, as the result of these various 
inoculations, some glasses with the Bactertum lactis, and some without it ; and, 
if it should turn out that all those glasses which contained the Bacterium lactis 
underwent lactic fermentation, and, on the other hand, those glasses which 
were free from bacteria had no fermentation, that would prove the point ; as, 
I think, you will agree with me, when we come to discuss the matter at a little 
more length after we have all our facts before us. Well, how were we to deter- 
mine the number of bacteria existing in the liquid? This was done in a simple 


348 ON THE NATURE OF FERMENTATION 


manner. A circular covering glass, just half an inch in diameter, was used. 
Of course, we know how many square thousandths of an inch there are in the 
area of this little glass. We also know by the micrometer how many thousandths 
we have across the field of our microscope, and, therefore, by calculation we 
know how many square thousandths there are in our field, and thus we can 
tell how many fields there are in the covering glass. To measure the liquid, 
I used this little syringe, with the piston rod in the form of a screw, on which 
revolves a disc, graduated for rooths of a minim; by which means you can, 
with perfect precision, emit 1-1ooth of a minim, or 2—1ooths, or any number 
you choose. I found that 2—100ths, or 1-5o0th, exactly occupied the covering 
glass ; so that, when it was put down upon a glass plate, with 1-5oth of a minim 
interposed, the rim of fluid round about the covering glass was not one-quarter 
of the diameter of the field, using the highest magnifying power ; so that prac- 
tically the liquid was all under the covering glass. I knew, therefore, that there 
was I-50th of a minim under the covering glass. If, then, I counted how many 
bacteria there were in a field, taking a number of different fields and striking 
an average, I could ascertain how many bacteria there were on the average 
in a field; therefore, by calculation, how many there were under the covering 
glass; or, in other words, how many there were in the 1-50th of a minim ; 
and, consequently, [ knew how much boiled water I ought to add in order that 
the drop, of whatever size I might wish it to be, should contain, on the average, 
one bacterium, and one only. This being done with a particular specimen of 
souring milk, I found that it was needful to add no less than one million parts 
of boiled water to the milk to ensure that there should be rather less than one 
bacterium, on the average, to every drop. Then with drops of that size I inocu- 
lated five glasses of boiled milk, and the result was that out of the five only 
one curdled ; but one did curdle and soured, and that one had the Bacterium 
lactis in abundance; the others did not curdle, underwent no fermentation 
whatsoever, and had no bacteria in them. ‘You may say, perhaps, ‘ How was 
it that there were none of these numerous different organisms and fermentations 
that you have been showing us?’ Simply for this reason, that although many 
other kinds of organisms undoubtedly did exist in the milk, yet most of them 
were in exceedingly small proportion to the Bacterium lactis, so that you might 
have searched, perhaps, for a whole day, with the high power of the microscope 
which it was necessary to use, and never discovered one. We are apt to forget 
how difficult it is to find these minute objects with high powers of the microscope, 
unless they are very numerous indeed. Therefore, when we came to dilute 
the milk with a million parts of water, the chances of getting anything but the 
Bacterium lactis were exceedingly small. It was with reference to the Bacterium 


ON THE NATURE OF FERMENTATION 349 


lactis that the dilution had been made, and not with reference to these other 
organisms relatively so rare. It happened that we saw in the souring milk 
before making the dilution that there was another kind of bacterium present, 
a moving kind different from the Bacterium lactis ; it was in every field, but 
not nearly so numerous as the Bacterrum lactis, and, consequently, it did not 
occur in the one milk that curdled. 

Now, therefore, we had every reason to hope that we had got the ferment 
pure, and thus we had the opportunity of performing other experiments ; and 
the last experiment that I shall mention is this. Having induced the lactic 
fermentation in another glass of pure boiled milk by means of our presumably 
pure ferment, and estimated the number of bacteria per minim, I diluted with 
boiled water accordingly and then proceeded as follows :—These five covered 
test-tubes which you see before you, containing boiled milk in their lower part, 
were inoculated each with a drop calculated to contain two bacteria ; these other 
five similar test-tubes were inoculated each with a drop calculated to contain 
one bacterium ; these five liqueur-glasses were also inoculated with drops each 
calculated to contain one bacterium ; and one other liqueur-glass with a drop 
calculated to contain four bacteria. The result was that the specimen with 
the drop calculated to contain four bacteria soured and curdled in a few days ; 
and all these five calculated to have two bacteria to a drop curdled also in a few 
days. The milk, you see, is perfectly solid. You will also observe that no 
change has taken place except the lactic fermentation, no Ozdium lactis has 
grown, and no other alteration has taken place ; it is as pure in whiteness as 
when it was first coagulated. I may here mention that, although all these 
glasses of milk coagulated, they did not do so at the same time. There was 
a time in the twenty-four hours during which the coagulation went on, in which 
I hoped that some of them were going to be permanently fluid, implying, as 
you would expect, that the particles of the ferment were not uniformly dis- 
tributed ; some had more than others, though each happened to have at least 
one. But, of the five test-tubes calculated to have only one bacterium on the 
average to each inoculating drop, three have remained fluid, and so have two 
of the liqueur-glasses ; so that, of the ten calculated to have on the average 
one bacterium each, exactly five, it so happens, have remained fluid without any 
curdling. I may consider myself somewhat fortunate that I have succeeded 
in bringing these specimens all the way from Edinburgh in this condition. 
I will now deprive this one of the protection in which it has hitherto lived. 
[Mr. Lister, having removed the glass shade and glass cap from one of the liqueur 
glasses, proceeded to drink part of its contained milk.} It is perfectly sweet. 
It has a slight flavour of suet, which M. Pasteur has described as resulting from 


350 ON THE NATURE OF FERMENTATION 


the oxidation of the oleaginous material of the milk. If any gentleman likes to 
taste it after the lecture, he can do so. 

Let me note this curious circumstance, that, of those specimens which did 
coagulate, those in the tubes coagulated considerably earlier than those in the 
more open vessels. At first, it seemed as if, for some strange reason, those in 
the open vessels were going to remain permanently fluid—even that which had, 
according to the calculation, four bacteria to the drop. I presume this is to 
be explained on the same principle as Pasteur has explained a corresponding 
fact with regard to the yeast plant. He has shown that, if a saccharine solution 
be put in a very thin layer in an open vessel with yeast, the yeast plant develops 
very rapidly, but very little fermentation occurs ; on the contrary, if it be put 
into a deep vessel, the development of the yeast plant does not go on so rapidly, 
but more fermentation results. He explains the fact in this way: that the 
yeast plant requires oxygen for its nutrition ; if it gets it easily, as it does in 
a shallow vessel in the air, it produces comparatively little effect in breaking 
up the sugar into its constituents, and vice versa. So here, in the test-tubes the 
carbonic acid accumulated, supposing any to exist, asin a well, and the Bacterium 
lactis had but little opportunity for getting oxygen. Accordingly here, 
just as in M. Pasteur’s experiments with a sugary solution with yeast 
in a deep vessel, the Bacterium lactis produced more rapidly its fermentative 
effect. 

But this, you say, is assuming that Bacterium lactis is the ferment. Now 
we are coming to that point. But first I have to mention an additional fact. 
For the satisfaction of others rather than for my own, I went through the 
laborious process of investigating portions of the contents of all these vessels ;. 
and I found that, in every one in which the lactic-acid fermentation had taken 
place, where there was curdling and souring, the Bacterium lactis was present ; 
and in no instance in which there was no lactic fermentation was any bacterium 
of any sort to be discovered. I believe that fact demonstrates that the Bacterium 
lactis is the cause of this very special lactic fermentation. Let us assume for 
a moment that there did exist some other material besides the Bacterium lactis 
in the milk capable of causing the fermentation ; that the lactic ferment was not 
the bacterium at all, but some chemical ferment. First of all, you will please 
to observe that we have from this experiment absolute evidence that the ferment, 
of whatever nature, is not in solution, but in the form of suspended insoluble 
particles. If the ferment had been in solution, every equal-sized drop of the 
water of inoculation would have produced the same effect. The fact that some 
drops were destitute of the ferment proves that that ferment was not in a state 
of solution. That is absolutely demonstrated. Now, suppose we admit, for 


ON THE NATURE OF FERMENTATION 351 


the sake of argument, that the lactic-acid ferment consisted of particles of some 
non-living substance, capable of self-multiplication as rapidly as the bacterium, 
but not living; a strange hypothesis, no doubt—but suppose we assume it. 
Suppose we admit that the true lactic ferment and the Bacterium lactis were 
merely accidental concomitants of each other, it would be absolutely incon- 
ceivable that these two accidentally associated things should be present in 
exactly the same numbers. And yet, according to the hypothesis, such would 
be only another mode of stating our observed fact, which amounts to this, that 
wherever there was a fermentative particle there was a bacterium, and wherever 
there was a bacterium there was a fermentative particle. But, suppose you 
admitted that—that there were exactly as many of the Bacterium lactis as there 
were of the hypothetical true fermentative particles—suppose you admitted that 
inconceivable thing, I say it would be again inconceivable that, if mutually 
independent, they should accompany one another in pairs, that invariably 
where there was Bacterium lactis there should be a ferment particle, and 
where there was no Bacterium lactis no ferment particle. That would be a 
thing as inconceivable as the other. Therefore, we have two inconceivables, 
one of which would have been sufficient to show that we cannot admit any 
other hypothesis than that Bacterium lactis is the cause of the lactic-acid 
fermentation. | 

But the experiment tends to even more than this. Where we find the 
effect so exactly proportioned, as regards the number of glasses affected with 
fermentation, to the adult bacteria that we count, we are led to infer that this 
particular bacterium, at all events, has not any spores—that there are no spores 
existing in addition to the bacteria. People seem often to assume that bacteria 
must necessarily have spores or germs. It seems to me an unlikely thing that 
they should. They are, as it were, a generative apparatus fer se, they are 
constantly multiplying; why should they have spores? I do not say that 
bacteria may not have spores. There are very different kinds of bacteria ; 
some may have spores, and some may not; but this sort of result seems to 
indicate that this particular bacterium has no spores ; at least, in the condition 
in which it exists in souring milk ; because, if we had, besides the bacteria that 
we can count, spores of bacteria disseminated through the liquid also, we should 
have the effect more than in proportion to the bacteria that we have counted. 
The only fallacy here is that it may be that the bacterium has not been diffused 
uniformly through the milk. Therefore, I do not say that in this case it is 
absolutely proved. But, at all events, this experiment gives us a line of inquiry, 
by means of which we may probably settle that point with regard to any 
individual case of bacterium. This, however, is a point I do not desire now to 


352 ON THE NATURE OF FERMENTATION 


insist on; but what I do venture to urge upon you is, that you will seriously 
ponder over the facts which I have had the honour of bringing before you to-day; 
and, if you do so, I believe you will agree with me that we have absolute 
evidence that the Bacterium lactis is the cause of the lactic-acid fermentation. 
And thus I venture to believe that we have taken one sure step in the way 
of removing this important but most difficult question from the region of 
vague speculation and loose statement into the domain of precise and definite 
knowledge. 


ON THE LACTIC FERMENTATION 
AND ITS BEARINGS ON PATHOLOGY * 


[Transactions of the Pathological Society of London, vol. xxix, 1878.] 


A FEW years ago it would have seemed very improbable that the souring 
of milk should have any bearings upon human disease; but all will now be 
ready to admit that the study of fermentative changes deservedly occupies 
a prominent place in the minds of pathologists. 

In order that any sure steps may be taken to elucidate the real nature 
of the various important diseases which may be presumed to be of a fermenta- 
tive nature, such as the specific fevers or pyaemia, the first essential, as it appears 
to me, is that we should have clear ideas, based upon positive knowledge, with 
regard to the more simple forms of fermentation, if I may so speak—more simple 
because they can be conducted and investigated in our laboratories. 

It may be said, indeed, that such information has been already afforded 
us by the researches of Pasteur and others who have followed in his wake, tending 
to prove that all true fermentations of organic liquids are due to the develop- 
ment of organisms within them; and I confess that for my own part I am 
disposed to agree with that view. But this opinion is by no means universal 
in our profession. We meet with statements by men of very high position, 
both as physiologists and pathologists, to the effect that in various fermenta- 
tions—such, for example, as putrefaction—the bacteria which are found to be 
present may, for aught we know, be mere accidental concomitants, not causes, 
of the fermentative change. And such being the case, it seemed desirable to 
obtain, if possible, entirely conclusive evidence upon the subject. 

About four months ago I made an attempt of this kind with regard to the 
lactic fermentation ; and I propose on the present occasion to bring forward 
the results arrived at, and at the same time to afford the members of the Patho- 
logical Society an opportunity of seeing with their own eyes samples of the 
preparations which resulted from that inquiry, and on which my conclusions 
are based. 

First, however, I desire to describe my method of experimenting, which, 


1 This communication, made to the Society without manuscript, on the 18th of December, 1877, is 
here given in its original form. In preparing it for the press, however, matter has been introduced 
including some points into which the time at my disposal did not allow me to enter, and also some 
facts since ascertained, together with considerations arising from them. 


LISTER I Aa 


354 ON THE LACTIC FERMENTATION 


in its present simplified form, has never been published. It is based, in the 
first instance, on the fact which experience has now amply demonstrated, that 
if we have a vessel like this liqueur-glass (A) in a state of purity, covered with 
a pure glass cap (B), the capped liqueur-glass being further covered with a glass 
shade (C), and standing as a matter of convenience on a plate of glass (D), any 
organic liquid contained in the liqueur-glass, provided it be free from living 
organisms at the outset, will remain without any organic development occurring 
in it as long as the arrangement of the glasses is left undisturbed. Or, in other 
words, although an interchange is constantly taking place between the gases 


led 
Nell 
4 ip; ; 

at eB 


FIG. 2. 


of the atmosphere and those in the liqueur-glass—for the cap does not fit at 
all, and the shade is not air-tight—yet the double protection of the glass cap 
and the glass shade effectually prevents access of the atmospheric dust to the 
liquid ; and if the dust is excluded, organisms do not occur in it. 

The glasses are obtained pure by means of heat. I find that exposure to 
a temperature of 300° Fahr. for two hours is sufficient to deprive all living 
material of its vitality. But it is not enough that the glasses should be so 
heated ; it is necessary that the air which enters them during cooling should be 
filtered of its dust. This I secure by heating them in a cast-iron box, the door 
of which (E) is here shown. This door has its circumferential part in the form 
of a groove, capable of being packed with a considerable mass of cotton-wool (F). 


* A curious exception to this general truth was met with by Mr. Godlee in the course of his experi- 
ments made by this method upon the vaccine virus, recorded in the Tvansactions of the Pathological 
Soctety, vol. xxviii. He found that Penicillium glaucum made its appearance in some of his glasses 
in a way that seemed unaccountable, till he discovered that the cupboard in which the vessels were 
kept was infested with acari, and that these creatures crawled up and into the glasses. He further 
found, on examining some of these acari under the microscope, that spores of the Penicillium were to 
be seen actually adhering to their hairs. The wonder now came to be, not that that fungus should 
have entered the glasses, but that other organisms, such as bacteria, should not have been also carried 
in. If there were any reason to apprehend the intrusion of such creatures, they might no doubt be 
easily excluded by placing each glass plate in an ordinary dinner-plate containing glycerine, so as to 
surround the glass plate on all sides with the viscid liquid. 


AND ITS BEARINGS ON PATHOLOGY. 355 


The door can be screwed by means of nuts (G, Fig. 3) against the edge 
of the box (represented by dotted lines in the sketch) ; and the cotton-wool, 
having the narrow rim of metal thus firmly pressed against it, serves as an 
effectual filter of the air that passes in during cooling. But then it is essential 
that the heat be so equably distributed as to avoid heating any portion of the 
cotton to such a degree as to destroy its physical properties. The cotton-wool 
which you now see in the 

lid has been used for several i Me 

experiments ; yet you ob- 
serve it is only slightly 
browned ; it is not singed 
at any part, as it would 
have been unless the heat 
had been nearly uniform. 
This uniformity of the heat 
is provided for by having 
three shelves of sheet-iron 
(H H H) interposed between 
the large Bunsen’s burner 
(I) and the bottom of the 
box, so as to prevent the 
heat from acting directly 
upon it; while at the same 
time the box is covered 
over with a cover of sheet- 
iron (KK), which reaches 
nearly to the ground, and, 
while it checks radiation, 
compels the heated air to 
travel over the whole ex- 
terior of the box and escape by holes at the top of the cover, whence it is 
conducted into a chimney by the tube (L). By these two means combined, the 
shelves below and the cover round about, we get the result which you see here. 
The cotton at the top of the box is browned to just the same degree as that 
at the bottom. Into such a box (about one foot in its three dimensions and 
furnished with a shelf in the middle) we may put a dozen sets of covered glasses 
such as I have described, together with their glass plates and shades. An aperture 
in the top of the box, well packed with cotton-wool, transmits the thermometer 


(M) to show when the temperature of 300° has been attained ; and when this 
Aa 2 


356 ON THE LACTIC FERMENTATION 


or any higher degree short of about 350° has been continued for two hours, 
the gas is turned off and cooling is allowed to take place ; and when the apparatus 
is quite cool, the covered glasses may be removed with confidence that they are 
perfectly free from living organisms. 

In the next place, how shall any pure organic liquid be introduced into one 
of these purified liqueur-glasses without risk of contamination? This we are 
now able to manage in a comparatively simple manner. The liquid is intro- 
duced by means of a flask of this form (N), having a bent spout, large at the 
commencement and comparatively 
narrow in its shorter terminal part 
(O) beyond the bend. The large size 
of the first part of the spout prevents 
it from ever acting like a syphon ; 
and the result is that, when liquid 
is poured from such a flask and the 
vessel is afterwards restored to the 
erect position, the end of the nozzle 
remains valved by a drop of the 
liquid ; and this guards the orifice, 
so that regurgitation of air can 
never take place through the nozzle. 
And the mouth of the flask being 
covered with pure cotton-wool (P), 
the air that enters the flask during 
the pouring out of the liquid is fil- 

Fic. 4. tered of its dust by passing through 

the cotton. When the decantation 

is completed, a piece of rag wrung out of a strong watery solution of carbolic 
acid (I to 20) is applied to the orifice of the nozzle, and, by capillary attraction, 
sucks out the drop; after which a cap of carbolized cotton-wool (Z in 
Fig. 6, p. 360) is tied securely over the nozzle, the ligature obtaining a pur- 
chase upon the projection (O) upon the tube.t. When this has been done, the 
liquid, if it was pure to start with, and the flask also pure, will remain 


* Cotton-wool intended for a cap to cover the mouth or nozzle of a flask is conveniently applied 
between two pieces of open muslin, which ensure that the cotton shall remain as a uniform layer, and 
also permit it to be readily removed without leaving any of the cotton adhering to the glass. The best 
material for the ligature I have found to be very fine iron wire, tied firmly in a half knot, which is 
secured by giving the ends of the wire a bend, so as to convert them into hooks. <A good mode of car- 
bolizing the cotton-wool is to treat it with a solution of 1 part of carbolic acid in 100 parts of anhydrous 
sulphuric ether. The cotton greedily imbibes the liquid into all its parts and the ether evaporating 
leaves the carbolic acid behind in the cotton, which is thus rendered highly pungent and antiseptic. 


ahs er 


ae 


a 


ee ee a 


AND ITS BEARINGS ON PATHOLOGY 357 


ready to be used again in a pure condition a month or even a year later if 
required, 

Now as to the means of preventing the entrance of dust into the liqueur- 
glass while it is being thus charged. Suppose I were going to charge this glass 
(Q) from this flask (the spout of which is alone given in Fig. 5), containing 
Pasteur’s solution introduced on the 7th of August, yet you observe, remaining 
as pure and clear as when it was first prepared, although it has served for charging 
various liqueur-glasses. I should remove the cotton cap from the nozzle, and 
instantly slip the end of the nozzle into the opening which exists in the centre 
of this half of a substantial india-rubber ball (Rk), 
previously steeped in a strong watery solution of 
carbolic acid. The caoutchouc absorbs carbolic 
acid into its substance, so that, even though dry 
after such steeping, it is powerfully antiseptic. I 
then remove the shade and take off the glass cap, 
and immediately substitute the cap of india-rubber 
on the nozzle of the flask (as shown in the sketch). 
Fluid is now poured in, the flexible caoutchouc 
acting as a hinge during the movements of the 
flask, while the antiseptic cap excludes all living 
organisms ; and the instant the flask is withdrawn 
the glass cap is replaced and the shade put on. 
The hemispherical form of the cap also prevents 
lateral currents of air from depositing dust on the 
drop at the nozzle while it is being moved from one glass to another, and a 
second, a third, or a dozen glasses may be thus charged in succession; and 
experience shows that this mode of procedure is so secure that the liquid will 
remain uncontaminated in such a series of vessels until it dries up through 
atmospheric influence. 

The last point is, How do we get the flask in a pure state with a pure liquid 
in it? The flask itself is purified together with its caps of cotton-wool over 
the mouth and nozzle by being heated in the hot box. And here we have another 
great advantage arising from the uniform temperature of the box sufficient to 
purify cotton without impairing its physical properties. We have, therefore, 
a simple means of securing a pure flask to begin with. 

Next, we wish to introduce into it a pure liquid. There is one organic 
fluid, peculiarly adapted for experiments on this subject, which can be got in 
the pure state with very little difficulty, and that is unboiled urine, provided 
we have a healthy urethra to deal with and a healthy bladder. All we have 


358 ON THE LACTIC FERMENTATION 


to do is to wash the surface of the glans penis thoroughly with a watery solution 
of carbolic acid, r to 40, in which strength it may be applied to the lips of the 
meatus urinarius without causing inconvenient smarting, and having thus 
merely purified the external integument, remove the cotton cap from the orifice 
of the flask and at once apply it to the organ and direct the patient to micturate. 
The purified glans takes the place of the caoutchouc cap, and as the urine enters 
no regurgitation of air is possible. As soon as the act of micturition is completed, 
a freshly carbolized cotton cap is tied over the mouth of the flask, and as surely 
as this process is properly performed, will you have the unboiled urine, together 
with its vesical mucus (which used to be regarded as the special ferment of urine), 
remain for any length of time free from development of bacteria or any other 
organism, and that whether the urine be acid or neutral in reaction.1 

: But suppose we have to deal with a liquid contaminated with organisms, 
like milk obtained from a dairy, we must purify it by heat. For this purpose 
I have always found exposure for an hour to a temperature of about 210° Fahr. 
sufficient.” 

I say 210°, not 212°, which is the boiling-point of water, because the way 
in which we have proceeded is, after introducing the liquid into the purified 
flask, to immerse the vessel, to a higher level than that of the contained liquid, 
in boiling water : and, in consequence of a certain degree of evaporation which 
takes place through the cotton caps which cover the mouth and nozzle of the 
flask, the temperature of the liquid is prevented from ever rising fully to the 
boiling-point. We thus avoid the occurrence of ebullition ; and this is a very 
great advantage, as we get rid of frothing; and, as already stated, the tem- 


* For further details on this subject, see Tvansactions of the Royal Society of Edinburgh, vol. 
XXVli, 1875, pp. 315 et seq. (p. 275 of this volume). 

* In making this statement I proceeded upon a pretty extensive experience with various liquids, 
such as water, Pasteur’s solution, and turnip infusion, as well as milk. In my experiments with the 
last-named liquid, I had obtained it fresh from the cow milked directly into a glass vessel purified with 
carbolic lotion and then rinsed with water, and having filtered it through a fine cloth, exposed it to 
heat with as little delay as possible. But between the time of the meeting of the Society and that of 
going to press, I have found that milk which has been kept for some hours cannot be purified so easily. 
This I am inclined to attribute to the fact that milk, unlike the other liquids referred to, is a hetero- 
geneous fluid containing oily particles in suspension, which tend as time passes to aggregate and coalesce. 
And it is quite conceivable that bacteria enclosed in such oily masses may be protected by them from 
the action of the hot watery liquid, the drops of butter acting as small portions of cheese have been 
found to do by some other observers. For it is a well-established fact that bacteria withstand a much 
higher temperature in the dry state than when acted on directly by hot water. I have also seen reason 
to believe that large numbers of bacteria grouped in masses are more resisting to the action of heat 
than isolated bacteria, as if the circumferential members of such a mass protected the central ones, 
and this circumference may perhaps aid in explaining the point in question. Again, if we consider 
the adventitious particles introduced in the form of dirt from the milkman’s hands, &c., we cannot be 
surprised that difficulty should be experienced even with fresh milk, unless special precautions are taken 
to promote cleanliness. 


AND ITS BEARINGS ON PATHOLOGY 359 


perature which is attained proves adequate for the destruction of organisms 
in the liquid. All we have to do then, supposing the interior of the flask per- 
fectly pure, is to introduce the liquid into the lower part of the flask with a view 
to immersion in a saucepan of boiling water: but then the most scrupulous 
care must be taken that no portion of the liquid so introduced shall come into 
contact with the upper parts of the interior of the flask; for any particles 
deposited there would fail to be acted on by the full heat of the water in the 
saucepan. Now the mode in which I filled the flasks in my earlier experiments 
was this. Having provided myself with a rag soaked with a strong solution of 
carbolic acid (1 to 20), I washed with it the exterior of a long funnel, and, wrap- 
ping the rag round the lower end of the funnel in sufficient mass to cover the 
mouth of the flask, I substituted the mass of antiseptic material for the cotton 
cap with which the mouth was previously covered, pushed down the funnel 
through the rag, poured in the liquid and withdrew the funnel, taking good care 
that the drop at its extremity did not touch the interior of the flask. A freshly 
prepared carbolized cotton cap was then applied to the mouth of the flask at 
the moment of withdrawal of the antiseptic rag, and the flask was immersed 
in the saucepan.' 

If I proceeded in this way with Pasteur’s solution or with turnip infusion, 
I always had success; but when I did the same thing with milk, time after 
time, to my great disappointment, I failed altogether. What was the explana- 
tion of the failure ? Some persons might have said, ‘Oh! the explanation is 
very easy to find. There are in milk complex organic molecules which, though 
as yet mere chemical substances, are, we imagine, ready to develop into living 
beings, and it is this complex constitution of the milk that makes you fail ; 
whereas, your Pasteur’s solution is a comparatively simple material, and turnip 
infusion may, for aught you know, have its molecules more simply constituted 
than milk.’ I felt sure that this was not the true explanation, but that there 
must have been some defect in my method of procedure. It may perhaps have 
occurred to some of you what that defect was ; it was this, that if we pour any 
liquid through a funnel, we invariably have air pass along with it. Air-bubbles 
consequently formed upon the surface of the liquid, and those bubbles bursting 
dispersed their dust in the air within the flask ; so that it might well happen 


* Means must be taken to prevent the flask from being floated up by the water in which it is 
immersed. This I have done by tying the flask into a vessel, such as a soap dish, containing shot. The 
flask so weighted is placed in the empty saucepan, warm water is poured in to a level considerably above 
that of the liquid in the flask, and brought to boil as quickly as possible and kept simmering for an hour. 
A piece of thin macintosh cloth, cut so as to adapt itself to the flask and cover the top of the saucepan, 
has the double advantage of preventing the water from boiling quickly away and avoiding moistening 
of the cotton about the flask by drops of condensed vapour. 


360 ON THE LACTIC FERMENTATION 


that such particles, including perhaps some atmospheric organisms, might be 
deposited upon the upper part of the vessel, and so fail to be destroyed when 
the liquid was heated. But why should success be more likely with Pasteur’s 
solution than with milk ? Simply for this reason, that milk is a material which 
serves as a pabulum for almost all organisms. I once met with a bacterium, 
but only once, that would not live 
in milk; for extremely numerous 
as the varieties of bacteria appear 
to be, almost all of them seem to 
thrive in that lquid, whereas it is 
a common thing to find bacteria 
which, if put alive into Pasteur’s 
solution, will not grow in it at all. 
The defect in our method having 
been discovered, there was no great 
difficulty in correcting it. It was 
done by substituting for the funnel 
this syphon (see Fig. 6), consist- 
ing of two glass tubes (S and T) 
connected by a tube of india-rubber 
(U), with a stopcock (V) in the course 
of the caoutchouc tubing. The sy- 
phon is first completely filled with 
water, the temperature of which 
should be higher than that of the 
air, so that there may be no dissolved 
air given off toform bubbles. Then 
suppose this (W) to be the fluid that 
we wish to introduce into the flask 
(X). We pass one leg of the syphon 
FiG._6. into it ; then turn the tap and permit 

a sufficient amount of fluid to flow 

out to ensure that all the water has escaped from the syphon; then turn 
off the stopcock and proceed in the manner already described for the funnel. 
The tube (T) having been washed with strong carbolic lotion, carbolized_rag is 
wrapped round its lower extremity, and this is applied to the mouth of the 
flask as the cotton cap is removed ; the tube (T) is pushed steadily down to 
the bottom of the flask through the carbolized rag (Y), the stopcock is turned 
on and the liquid passes into the flask without the smallest air-bubble accom- 


% AND ITS BEARINGS ON PATHOLOGY 361 


panying it. When a sufficient quantity has been introduced, the tap is again 
turned off, and the syphon is withdrawn through the antiseptic rag, and a fresh 
cap of carbolized cotton is tied over the mouth of the flask when the rag is 
withdrawn. 

I have said that before I saw my mistake in using the funnel, I never 
succeeded with milk. Since I have adopted the syphon I have charged many 
flasks and never failed. Here is a flask of boiled milk (or rather of milk that 
has been exposed to a temperature of 210°) prepared on the 7th of August, and 
remaining we may safely say as pure as it was then. You observe it is still 
perfectly liquid and unaltered in appearance. Now I venture to remark that 
this failure and correction of the failure are extremely instructive, as showing 
how the development of organisms under circumstances in which we cannot 
at first explain their occurrence may be really due to fault on our part, defect 
in our own manipulation. 

So much for our method of procedure. I will now go on with the main 
subject of this communication. I selected the lactic fermentation as one pecu- 
liarly favourable for investigation : first, because the effects which it produces 
in milk are extremely striking and readily recognized—the solidification which 
takes place being obvious at a glance, and the souring as shown by test paper 
being also a very conspicuous change; and in the second place because the 
ferment which occasions these alterations is, in ordinary localities, a very rare 
ferment ; and if it be rare, it is not likely that any defects in our manipulations 
will lead to its accidental introduction. 

It may seem strange that the ferment that leads to the souring of milk 
should be rare, but such is the fact ; in dairies it appears to be universal, but 
in the world at large it is scarce. If you charge a series of pure liqueur-glasses 
with boiled milk and take off their caps so as to expose them to the air for about 
half an hour each, doing this for the various glasses at different times of the 
day or in different rooms, you will be sure to have organisms develop in all 
of them, of the nature of filamentous fungi and bacteria; and you will see 
fermentative changes ensue; but, so far as my experience goes, you will not 
see the coagulation and souring of the lactic fermentation, nor will you find 
under the microscope the peculiar organism to which I have given the name of 
Bacterium lactis, which is represented here (Plate XIV, Fig. 9) as it occurs in 
ordinary curdled milk, and which may be seen under one of the microscopes on 
the table, in milk taken from the cow yesterday. 

This organism is a motionless bacterium, that is to say, exhibiting no move- 
ment except a slight jogging, occurring most commonly in pairs, but frequently 
in chains of three, four, or more individuals, each segment being of somewhat 


362 ON THE LACTIC FERMENTATION PR 


rounded form, more or less oval, with the long diameter in the direction of the 
length of the chain, and often showing, on careful focusing, a line across their 
central part indicating transverse segmentation. They vary in diameter, as 
I shall have occasion to notice again, full-sized specimens measuring about 
1-20,000th inch.t You always find them, as far as I know, in souring milk 
from a dairy, and a touch with the point of a needle which has been dipped into 
such souring milk will induce their development with great rapidity in a glass 
of boiled milk, together with the characteristic curdling and souring, showing 
that the boiled milk is thoroughly disposed to the lactic fermentation as 
soon as the appropriate ferment enters, while that ferment, as already stated, 
is not likely to occur as the 
result of exposure to the air 
of your study or any ordinary 
situation. 

These little glasses (repre- 
sented on a reduced scale in 
Fig. 7) illustrate the same 
point as regards unboiled milk. 
Each is a small test-tube pro- 
vided with a cap made of the 
bottom of a larger test-tube, 
and arranged along with five 
others in a stand made of 
pieces of glass tubing and 
stout silver wire, and placed 

acne under a common glass shade 

ona plate of glass. Four such 

sets of glasses, making twenty-four glasses in all, were purified by heat in the hot 
box, together with their plates and shades. Another larger glass, provided with 
a glass cap, having been also purified by heat in the box, milk was drawn directly 
into it from a cow standing in a little orchard belonging to a dairy farm and 
within two yards of the dairy itself, the glass cap being removed immediately 
before the milking commenced, and reapplied as soon as the vessel was charged, 
the quantity amounting to about two ounces. Then by means of a syringe 
connected with a purified pipette the milk was at once transferred, in a room 
in the farm-house, to the little glasses, each cap being replaced as soon as the 
glass was charged. Yet in spite of the care that was taken, organisms must have 


* In giving these as the characters of the Bacterium lactis, I do not wish to be understood as stating 
that this species can always be certainly recognized by its morphological features alone. 


AND ITS BEARINGS ON PATHOLOGY 363 


entered from the air of the orchard or of the apartment, possibly also from the 
cow’s teat (though this had been previously washed by drawing milk from it 
just before the glass was charged) ; for you observe every one of the twenty-four 
glasses shows manifest evidence of alteration, and there can be no doubt that 
these changes are due to the development of organisms. No fewer than seven 
of them are seen, by aid of a pocket-lens, to contain filamentous fungi of various 
sorts, for aught I know undescribed, and certainly none of those commonly met 
with in milk." 

Two of the glasses containing filamentous fungi are represented of natural 
size in the sketches reproduced in Figs. 1 and 2, Plate XIV. The other glasses 
present appearances which members of the Society, if they will examine them, 
will find to be exceedingly peculiar. No two are alike: some have a golden- 
yellow aspect (Fig. 8), some a green tint (Fig. 7), while many are studded with 
brilliant red spots (Figs. 3, 4, 5 6) either alone or associated with other colours, 
and the lower parts of the contents of the several glasses are changed to various 
degrees of translucency and shades of tint, implying different fermentative 
changes. But there is no reason to suspect in any of them the occurrence of 
the Bacterium lactis, or the lactic fermentation. I have not had opportunity 
to examine the contents of these glasses microscopically, but in another experi- 
ment made in the same way a few days previously with twelve similar glasses 
I found, just as here, some affected with filamentous fungi, and the majority 
altered in various ways in colour, including definite specks of different shades 
of orange growing gradually as the red ones in this set did from a mere speck 
to larger and larger spots; and, examining with the microscope the contents 
of every one of those glasses, I found the orange specks to be composed of 
organisms in the form of little spherical granules peculiarly grouped, which 
I have elsewhere described under the name of Granuligera ;* and other glasses, 
having alterations without such bright and definite colours, presented bacteria 
of different appearances, but in no case did I find the Bacterium lactis. 

I also performed other experiments of a very simple character which illus- 
trate equally well the rarity of the lactic ferment in the air, even though it be 
the air of a cow-house. The teat of the cow and the milkmaid’s hands having 
been washed with strong watery solution of carbolic acid, milk was received 
directly into a purified flask of the kind above described (p. 356), and from this 
a dozen purified liqueur-glasses were charged in my study within about half an 

* The filamentous fungi most frequently found in milk that is kept for a considerable period are 
the Oidium lactis, the common blue mould Penicillium glaucum, the common green mould of cheese, 
Aspergillus glaucus, and two forms of Mucor, the M. mucedo and M. racemosus. 


*See Transactions of the Royal Society of Edinburgh, loc. cit., p. 319, and Plate (p. 275 and Plate VI of 
this volume). 


364 ON THE LACTIC FERMENTATION 


hour. All these glasses underwent fermentations, and exhibited organisms under 
the microscope, but none showed the lactic fermentation or the Bacterium lactis. 

With regard to the cause of the strange, perhaps unprecedented, appear- 
ances presented by the milk in the little glasses shown to the Society, the explana- 
tion undoubtedly is, not that organisms of a specially rare kind were here present, 
but that species, perhaps exceedingly frequent in other media, had an excep- 
tional opportunity for coming forward in milk, in consequence of the exclusion 
of ferments such as the lactic, the butyric, &c., which, when present in milk, as 
they commonly are, take the precedence of others, and so alter the fluid as to 
render it an unsuitable pabulum for the multitude of other kinds. 

Here I have another set of little test-tube glasses, twelve in number, with 
which the same experiment was repeated two days later, only with still more 
careful precautions against the entrance of organisms from the air or from the 
teat ; but even here, although the appearances are less conspicuous than those 
in the other twenty-four, a careful inspection shows that, in ten out of the twelve, 
organisms of one kind or another have entered, but two of them remained per- 
fectly unchanged in aspect six weeks after the performance of the experiment, 
and on examining the milk from one of these I found it fluid, perfectly natural 
in reaction and in taste, and free from any organisms that could be discovered 
by the microscope. Thus was at length attained the object of these experi- 
ments with the little glasses, viz. the proof that unboiled milk, as coming from 
a healthy cow, like urine from a healthy bladder, really contains no material 
capable of giving rise to any fermentative change or to the development of any 
kind of organism which we have the means of discovering. 

The lactic ferment is as scarce in ordinary water as we have seen it to be 
in the air. If I prepare a series of glasses of boiled milk in the way that has 
been described, and add to each a drop, say half a minim, of tap water, I find 
that fermentative changes, such as putrefactive or butyric alterations, occur in 
all, but that none exhibit the souring or curdling of dairy milk. An extremely 
instructive experiment is to inoculate each of a series, say ten, of such glasses 
with a very small drop of a constant size for all, which can be readily done by 
means of a syringe like this (Fig. 8), having a graduated nut (a), revolving 
on a fine screw on the piston rod (6), each degree on the nut corresponding to 
I—1ooth minim, so that either 1-10oth, or 1-5o0th, or 1—2o0oth, if it be desired, 
can be expelled at pleasure Supposing 1-100th minim of water to be thus 


* It is essential to the precise working of this apparatus that there be nothing elastic in its com- 
position, otherwise drops of varying size will be furnished by it. Thus, an india-rubber junction between 
the syringe and the nozzle is inadmissible. The nozzle of glass tube (c) is screwed upon the body of the 
syringe by means of the brass adapter (d), to which the glass tube is secured with a cement which I have 
found very useful on account of its power of resistance to the action of boiling water, viz. finely powdered 


AND ITS BEARINGS ON PATHOLOGY 365 


introduced into each glass, the result will probably be that fermentative changes 
of totally different kinds will occur in the various glasses, as indicated by striking 
differences of colour in the contained milk and differences of odour in the air 
in the glass shades ; and, what is extremely interesting, some 
glasses will escape all change. This last fact proves at once 
the important truth that the fermentative agency in water, 
the existence of which was pointed out long ago by Dr. 
Burdon-Sanderson, is not matter dissolved in the water, but 
consists of insoluble particles of some kind or other suspended 
init. For if the ferment were dissolved in the water, every 
equal-sized drop would produce an equal effect. But the 
fact is, as already stated, that when drops of such minute- 
ness are employed, some of the inoculated glasses escape 
altogether, and those which are affected exhibit different 
kinds of fermentation, and we thus learn from this simple 
experiment not only the truth that the fermentative material 
is in the form of insoluble particles, but that every minim 
of ordinary water contains several different kinds of fer- 
ments, which, though generally confused through being 
mixed up together, declare their individual peculiarities 
when isolated by this method of separation. 

These various fermentative changes were -invariably 
found associated with bacteria, those in different glasses 
sometimes showing themselves conspicuously different under 
the microscope, though often only distinguished by their 
effects. Thus, in one case, the cream being particularly thick, 
a bright vermilion-coloured point appeared after some 


gum copal brought to a liquid state by a high temperature and then applied to 
the objects to be cemented, which have previously been heated to an equally 
high degree. The presence of an air-bubble in the water within the syringe 
would also by its elasticity vitiate accuracy of performance. This is got rid 
of, so far as the body of the syringe is concerned, by first accurately charging 
it with water that has been boiled to dispel its dissolved air. The water of 
inoculation, with which the glass nozzle is to be filled, is also raised to a 
somewhat higher temperature than the air of the apartment by placing the 
vessel containing it before the fire for a few minutes. The nozzle with its Fic. 8. 
adapter is purified by boiling it in water in a saucepan for about half an hour, 

after which its fine end is immersed in the water for inoculation, and when 

it is filled beyond the bend the other end is depressed, so that the rest of the filling may be done by 
syphon action. When a drop of water projects from the adapter, it is applied to a correspondingly 
projecting drop of water at the mouth of the syringe, and the two drops coalescing prevent the in- 
troduction of a particle of air when the nozzle is screwed on. With these precautions drops of exactly 
the same size can be ensured. 


366 ON THE LACTIC FERMENTATION 


days at the spot of inoculation, and gradually spread over the surface, and on 
examining with the microscope a portion taken with a purified needle from 
the vermilion spot, I found it teeming with bacteria, while a portion of 
the uncoloured cream in the vicinity showed nothing but the usual milk 
globules. Here then was a remarkable change going on in the milk fart 
passu with the development of bacteria, and doubtless occasioned by them, 
vet the bacteria themselves were of ordinary double-rod form and of about 
medium size... But various as were the changes produced in the milk by 
inoculation with water, there was no instance in the course of several such 
experiments of the lactic fermentation resulting from it. We see, therefore, 
from the facts which I have adduced, that the souring of milk, instead of being— 
as might naturally be supposed a priovt from seeing it occur constantly in all 
milk brought from a dairy—an inherent property of the liquid, is a change 
which, whether in boiled milk or unboiled, requires the introduction of something 
from without, and that something a scarce article, both in air and in water, 
except in dairies. Indeed, even in a dairy, though it exists in all the milk in 
the pans, it does not necessarily follow that it is the most frequent ferment in 
the air. I once took a glass of pure boiled milk to a dairy, and putting it down 
near one of the pans, removed its glass shade and glass cap, and left it exposed 
for a quarter of an hour, thinking it probable that the lactic fermentation would 
result. But it so happened that this was not the case. As a consequence of 
this exposure a filamentous fungus made its appearance in the milk, and also 
a bacterium, but a bacterium associated with a most extraordinary alteration, 
viz. viscidity in an extreme degree, reminding me of that of the glutinous drops 
that bead the spider’s web. On introducing a needle into the top of the liquid, 
and raising it, I drew out a barely visible thread, which was a yard and two 
inches long before it broke. Such was the special fermentation that resulted 
from exposure to the air on that occasion even in a dairy ; it so happened that, 
if any particles of the lactic ferment were floating in the air at all, none fell into 
the glass. 

This particular fermentation, therefore, from the conspicuousness of its 
effects and the rarity of the ferment under ordinary circumstances, seemed 
a peculiarly favourable one for investigation. 

And now, before proceeding further, I desire to correct a mistake into 
which I fell when investigating this same fermentation some years ago; for, 
next to the promulgation of new truth, the best thing, I conceive, that a man 
can do, is the recantation of published error. In the year 1873, I gave, in the 


* These experiments were performed in the early part of the year 1875, and were briefly alluded to 
in a paper in the Lancet of that year (see Lancet, April 3, 1875, p.470). Reprinted in vol. ii, p. 226. 


AND ITS BEARINGS ON PATHOLOGY 367 


Microscopical Journal, an account of the behaviour, as I supposed, of the Bac- 
tertum lactis in different liquids. I stated that, having obtained souring milk 
from a dairy, I inoculated a glass of uncontaminated unboiled urine with a small 
drop, and the result was the development in that liquid of organisms with a 
very different appearance from the bacteria which I had seen in the souring 
milk. The latter had the characters of Bacterium lactis, as already described 
(Plate XIV, Fig. 9), viz. pairs or chains of small oval bodies, with lines of trans- 
verse segmentation. Those in the urine, on the other hand, were broad and 
extremely long, often coiled up like a spirillum, though motionless, like the 
Bacterium lactis. There were, however, what certainly looked like transitional 
forms between the two. From this urine I inoculated another glass of the same 
liquid, the result being a reproduction of the same large spirillum-like organism. 
I next inoculated from the second urine-glass one of Pasteur’s solution ; and 
now obtained appearances different from any before seen, viz. instead of either 
the motionless chains of Bacterium lactis of the milk, or the spirillum of the 
urine, an actively moving minute double bacterium. But on introducing a 
small drop of the Pasteur’s solution so peopled into a third urine-glass, I got 
back large coiled organisms resembling those of the former glasses of the same 
fluid, except that these exhibited languid motion. Yet the introduction of 
a small drop from this third urine-glass into one of pure boiled milk was followed 
by souring and curdling just as if the inoculation had been made with sour 
milk from the dairy. The apparently transitional forms in the first urine-glass 
made me suppose that the spirillum was the Bacteriwm lactis, modified by its 
new habitat. I also examined in a cultivating glass, under the microscope, 
a drop of a mixture of fresh urine with a small quantity of the Pasteur’s solution 
containing the moving bacteria, and found that the minute active organisms 
first seen gave place to larger languidly moving specimens, and thus I thought 
I had evidence of a transition from one to the other. And lastly the efficiency 
of the contents of the third urine-glass as a lactic ferment, in spite of the various 
forms assumed in the various media, confirmed my belief that I was observing 
one and the same organism in all the glasses. And if this was really the case, 
considering how thoroughly the organism must have been washed in the various 
media of all chemical material that might be supposed to be originally associated 
with it in the milk—particularly considering that the lactic fermentation does 
not occur at all in either urine or Pasteur’s solution—the chain of facts appeared 
a strong confirmation of the view that this particular bacterium was really the 
cause of the lactic fermentation. I was mentioning these facts a few months 
ago to an eminent physiologist, who took the view that after all bacteria might 


* See Quarterly Journal of Microscopical Science, October 1873 (p. 309 of this volume), 


368 ON THE LACTIC FERMENTATION 


be mere accidental concomitants of the fermentative changes ; and when I had 
finished my story he said, ‘ Well, I am convinced.’ I thought to myself, ‘ If 
I have convinced this eminent teacher by these facts, they are worth proving 
more rigorously ; I shall have a little time between giving up my surgeoncy 
in Edinburgh and going to London, and I will devote it to repeating the experi- 
ments ; but this time I will make continuous observations under the microscope, 
and trace, if I can, the actual process of transformation of the organism from 
one form to another.’ Accordingly, I got some souring milk from the same 
dairy as before, and proceeded, in the first place, to inoculate from it a glass 
of uncontaminated unboiled urine, and also a glass of pure Pasteur’s solution. 
The result in the case of the urine was that, instead of getting a large motionless 
spirillum as in the corresponding experiment of four years previously, I found 
an active double bacterium of moderate dimensions. In the Pasteur’s solution, 
on the other hand, instead of the minute very actively moving bacterium of my 
former experience, I obtained only motionless bacteria of various dimensions. 

Here then were the facts all wrong. What was the explanation? I had 
obviously got some accidental contamination of the Bacteriwm lactis with other 
forms, although in doing the inoculations I had only introduced a very minute 
portion with the point of a heated needle. So I determined to try if possible 
to get rid of concomitant bacteria of other kinds, and the way which occurred 
to me as a possible mode of doing this was to dilute the souring milk with so 
large a quantity of boiled and therefore pure water as to have on the average, 
so far as it could be estimated, only one bacterium of any kind to every one 
of the drops with which a set of glasses of boiled milk should be inoculated. 
If this could really be done, as the Bacterium lactis was certainly in much larger 
numbers than any other kind, I might hope that some at least of the drops of 
inoculation might contain it isolated from other species, and that thus I might 
have the Bactertwm lactis develop pure and unmixed in the inoculated milk. 
Accordingly having obtained some souring milk from the dairy, I inoculated 
a glass of boiled milk from it by dipping the point of a heated needle successively 
in the two liquids, and when the odour of souring milk was perceptible in the 
air under the glass shade, I found bacteria present on microscopic examination, 
and endeavoured to estimate their numbers in proportion to the liquid. 

This was done in the following manner. By means of the syringe already 
described (p. 364) one or more hundredths of a minim could be measured with 
precise accuracy ; and I found that 1-50th minim exactly occupied a circular 
plate of thin covering glass, half an inch in diameter, so that when such a drop 
was placed on a glass slide, and a covering glass of the size mentioned and quite 
flat was put down upon it, all air was expelled from under the latter, and the 


AND TITS BEAKINGS ON PATHOLOGY 369 


rim of fluid that formed round about its margin was so narrow as not to measure 
a quarter of the diameter of the field of the microscope even when the highest 
magnifying power was used. In other words, 1-50th minim was disposed in 
a thin uniform layer of the exact size of the covering glass. Hence the number 
of bacteria under the glass slip, that is to say in I-50th minim, was equal to 
the number of the bacteria in a field of the microscope multipled by the number 
of times the area of that field went into the area of the covering glass. The 
micrometer gave the diameter of the field in thousandths of an inch; and the 
covering glass measured 500-thousandths of an inch across: and the areas of 
the circles were of course proportioned to the squares of those diameters. All 
that was needful, therefore, in order to enable me to calculate the number of 
bacteria in 1-50th minim, was to form a fair estimate of the number of bacteria 
per field, and this was done by counting the organisms in a considerable number 
of fields and taking the average.* 

It so happened that two kinds of bacteria were seen under the microscope, 
one motionless, with the characters of Bacterium lactis, the other much less 
numerous, with longer segments and in active movement. Asa rule, on examin- 
ing milk which is undergoing the lactic fermentation but is still fluid, the 
Bacterium lactis is alone discoverable ; but in this instance we had ocular proof 
of the admixture of another sort, though in much smaller numbers. As the 
result of the estimate which I made of the number of bacteria present in every 
1-50th minim, I found it necessary to dilute the milk with no less than a million 
parts of boiled water in order that every 1-10o0th minim should contain on the 
average a single bacterium.? This having been done, 1-rooth minim of the 


* I found great advantage from placing the circular covering glass (with the liquid) on the under 
surface of a plate of thin glass, large enough to cover a chamber excavated in a thick glass plate. A 
drop of water sufficed to fix the edges of the thin plate of glass down upon the thick, and served also 
to prevent any evaporation taking place from the liquid to be examined into the air-chamber, so that 
the liquid was maintained of constant quantity. At the same time, the object being on the under side 
of the thin plate of glass, an immersion lens could be used for examining it to its extreme limits without 
the inconvenience of the liability of the drop of water under the object glass mingling with the liquid 
examined, as would have been the case had the object been on the upper side of the glass 
plate. 

* The dilution with this enormous proportion of water was readily done by dividing the process 
into two stages. First, by means of the small syringe (figured at p. 365) with purified nozzle, 1-100th 
minim of the milk was added to 200 minims of boiled water, which had been measured into a purified 
glass by means of a pure graduated pipette connected with a syringe, the end of the pipette adapted 
to the syringe, having been stuffed with cotton-wool before purification in the hot box, soas to filter air 
that passed into the pipette from the syringe. When the milk had become thoroughly diffused through 
the water, as indicated by uniform opalescence (the diffusion having been promoted by stirring rapidly 
with a pure glass rod), a minim of this first dilution was transferred by means of another and smaller 
pure syringe-pipette into a second purified glass, which had been charged with 50 minims of boiled water. 
I need hardly add that the utmost care was used to avoid more than momentary exposure of the 
liquids manipulated, and of the purified pipettes or other apparatus employed. 


LISTER I Bb 


370 ON THE LACTIC FERMENTATION 


infected water was added by means of the small syringe? (figured at p. 365) to 
each of five glasses of pure boiled milk. The result of this inoculation was 
that one only of the five glasses was affected at all. The contents of four 
remained permanently fluid and unchanged, and when examined with the 
microscope after the lapse of thirteen days, showed no bacteria of any kind. The 
milk of the fifth glass, however, was, in the course of the third day after inocula- 
tion, converted into a solid mass, and on examination was found to be sharply 
acid, and under the microscope there were seen among the granular masses of 
caseine countless motionless bacteria with the ordinary characters of Bacterium 
lactis, specimens of which were sketched and are reproduced in this diagram 
(Plate XIV, Fig. 9). No other bacteria, however, were to be discovered ; we 
had got rid of the moving species which was seen to be associated with it in 
the milk before dilution, and a fortiori it might be believed that other species, 
doubtless present in the original milk, but in too small numbers to be detected, 
had been avoided. 

Having therefore presumably obtained the Bacterium lactis pure and un- 
mixed, I proceeded to ascertain its behaviour in other media. I inoculated 
a glass of uncontaminated unboiled urine with it; and now, instead of either 
the moving bacterium which resulted from a corresponding inoculation with 
sour milk a few days before, or the large coiled organism of the experiments 
done four years previously, there appeared a motionless bacterium with identi- 
cally similar characters to those of the Bacterium lactis in the glass of milk, 
as will be seen from this diagram (Plate XIV, Fig. 10) made from a sketch taken 
two days after inoculation of the urine. Had either of the forms seen in the 
previous experiments been present, the insignificant motionless Bactertum lactis 
would probably have escaped notice altogether. In the course of the first 
twenty-four hours its growth was indicated by delicate white vertical streaks 
on the glass without any turbidity of the liquid. Next day, however, the fluid 
was decidedly nebulous, but after that period the growth was exceedingly slow, 
and very little effect was produced upon the urine as regards either odour or 
reaction. Nevertheless it still retained its power of acting as a lactic ferment 
when introduced into milk even after four days’ residence in the urine; for 
having inoculated at this period eight glasses of boiled milk with drops of the 
urine diluted with enough boiled water to provide about three bacteria on the 
average to each drop, all the glasses soured and curdled within three days.? 

On the day on which this fact was observed, and when the bacterium was 


* The nozzle of this syringe was purified by boiling it in water in the interval between its employ- 
ment referred to in the above note and the inoculation of the milk-glasses. 

* Even after seventeen days in the urine the organism still retained the power of causing lactic 
fermentation, though it was then not quite so energetic, requiring an additional day to produce curdling. 


AND ITS BEARINGS ON PATHOLOGY Sy jt 


therefore still in full activity, I introduced a small portion of the curd from 
one of the glasses into a glass of Pasteur’s solution, in order to study the 
behaviour of the organism in that fluid. In this experiment I made use of what 
I have called a ‘ separation-tube ’, a piece of glass tube bent at an angle of about 
45° (see Fig. 9), with one leg shorter than the other, the shorter leg closely 
packed with moist cotton-wool (e), which is purified together with the tube 
by boiling in water. The apparatus is then transferred to a pure liqueur-glass, 
in which it is arranged with the longer leg (/) placed vertically and kept in this 
position by a mounting of silver wire (g) applied to the tube before its purifica- 
tion. The liquid to be experimented on is now poured into the glass to a higher 
level than the mouth of the shorter leg of the separation tube, but not so high 
by a considerable interval as the top of the longer leg. 
The liquid finds its way slowly through the cotton and rises 
in the longer leg, and it is into the liquid in the longer leg 
of the separation tube that the material of inoculation is 
introduced. The cotton in the shorter leg is so closely 
rammed that it serves as an effectual filter to prevent the 
passage of any particles of ordinary solid matter; but if 
any organism capable of developing in the liquid is intro- 
duced into the longer leg, it will work its way through the 
cotton, and show itself in the general liquid in the glass. 
Even a motionless bacterium or a filamentous fungus will 
traverse the closely packed mass, at a rate corresponding 
with the rapidity of its development. Thus we have a 
simple means of separating things which are living and capable of developing in 
any particular liquid from particles which are not alive, or which, though 
living, are incapable of growing in that medium. It was into the longer leg 
of such a separation-tube in a glass of Pasteur’s solution that I introduced 
the morsel of curdled milk containing the actively growing Bacterium lactis. 
For a long time it appeared as if no growth whatever of the organism had 
taken place in its new habitat. But when nearly three weeks had elapsed, 
thinking that the little bit of curd looked somewhat swollen, I subjected 
it to microscopic examination, and found that the substance of the curd 
seemed to have disappeared, its place being occupied by small bacteria 
having the characters of Bacterium lactis, showing that the organism really 
had undergone some development. But it seemed to have grown only where 
it had the material of the curd to feed upon; for the outside liquid in the 
glass showed no trace of any organism either to the naked eye or under the 
microscope. Thus it appears that the Bacterium lactis, though not destroyed 
Bhi2 


372 ON THE LACTIC FERMENTATION 


by Pasteur’s solution, does not find in that fluid the materials requisite for its 
nutrition. I also imitated in another glass of Pasteur’s solution the experiment 
of four years before, by inoculating it with urine in which the Bacterium lactis 
was developing actively, but here again, although the specimen was kept twenty- 
one days, no sign whatever of bacteric growth appeared. It was therefore plain 
that the Bacterium lactis is really incapable of growing in pure Pasteur’s solution.t 

Thus I was forced to the conclusion that the appearances which I had 
described in my former communication as due to modifications of the Bacterium 
lactis in urine and Pasteur’s solution had been entirely deceptive, and had been 
occasioned by the accidental accompaniment of other species. And now that 
we know from the results of experiments like those with the little test-tube 
glasses how very numerous are the bacteria and other organisms which really 
infest milk, it is easy to understand how such a confusion may have arisen.” 

Now, however, having good reason to believe that I had got the Bacterium 
Jactis pure and unmixed, I proceeded to perform the experiment which con- 
stitutes the most important feature of this investigation. I have already 
described the mode of procedure when speaking of the means adopted for isolat- 
ing the Bacterium lactis. Its object now was to obtain, if possible, absolute 
proof, which would commend itself to the judgement of all, that the Bacterium 
lactis is really the cause of the lactic fermentation, and no mere accidental 
concomitant of the change. 


* It is right that I should state that the solution which I employed differed from that made accord- 
ing to Pasteur’s formula, in having only half the proportion of sugar, and in having its mineral salts 
derived from wood ashes instead of from the ashes of yeast. It was, however, with solution of precisely 
the same composition that I had worked in the experiments of four years previously. 

* It is not, indeed, altogether easy to see what the precise train of events may have been in the 
experiments of four yearsago. I may suggest the following as possible. First, along with the Bacterium 
/actis with which the first urine-glass was inoculated (see p. 367), was accidentally introduced another 
kind of bacterium, which produced the large spirillum-like appearances. This adventitious organism 
grew freely in the urine, along with the slowly growing and inconspicuous Bacterium lactis. It presented 
considerable varieties of form, some of them closely resembling chains of Bacterium lactis, but it was 
in reality a totally distinct species. Then when the Pasteur’s solution was inoculated from the urine, 
both organisms were again introduced together. Here the spirillum-like organism underwent a 
modification, assuming the characters of an actively moving double bacterium, a transition which was, 
I think, sufficiently traced under the microscope (see Microscopical Journal, loc. cit.). Meanwhile, the 
Bacterium lactis lay dormant in this medium, but retained its vitality, and by accident it happened 
that one or more of these still living individuals, lying perhaps at the surface of the liquid in the speck 
of scum that commonly results from inoculation, was transferred along with the other organism to the 
last urine-glass. Here the latter resumed the spirillum-like form which it had before shown in urine, 
though retaining now for a while in a limited degree the movement it had acquired in Pasteur’s solution. 
The individual or individuals of the Bacterium Jactis introduced into the urine along with it were here 
able to develop again, though slowly, and some of their progeny entered the glass of boiled milk inocu- 
lated from this urine-glass, and in that medium developed with their accustomed rapidity and with 
the usual fermentative effect. It may, perhaps, seem trivial to record this complicated hypothetical 
explanation, but I am induced to do so for the sake of illustrating the excessive care required in order 
to avoid deception when we are dealing with such extremely minute organisms. 


AND ITS BEARINGS ON PATHOLOGY 373 


On the 30th of August last, having provided sixteen pure glasses of boiled 
milk, and having estimated, in the manner already described, the number of 
bacteria present in every I-50th minim of a glass of boiled milk which had 
been inoculated the day before by touching it with a heated needle dipped in 
milk curdled under the influence of the pure ferment, I diluted a drop of this 
milk with boiled water to the requisite degree, and introduced into each of 
ten of the sixteen uncontaminated glasses a drop calculated to contain on the 
average a single bacterium, while five of the rest received each a drop supposed 
to contain two of the organisms, and the remaining glass was inoculated with 
a quantity in which, according to the estimate, there would be four bacteria. 
The result was that within three and a half days the glass into which four 
bacteria were supposed to have been introduced contained a curdled mass, 
and the five which had received the drops arranged for two bacteria each had 
all undergone a similar change. Of the ten inoculated with drops averaging 
one bacterium each, the majority were at this period still fluid ; but some assumed 
the solid condition in the course of the next twenty-four hours, though at 
different times. But of this series of ten exactly five, as it so happened, remained 
permanently fluid. 

This was just the sort of occurrence which might have been anticipated 
if we believed the bacteria to be really the cause of the fermentative change, 
and supposed that we had succeeded in forming a fair estimate of their numbers. 
It was to be expected that the bacteria would not be distributed with perfect 
uniformity in the water with which the milk was diluted; and hence, of the 
drops containing on the average one bacterium each, some would probably be 
destitute of the organisms, and the rest have more than one, and in differing 
numbers, involving slight differences of time in arriving at the stage of the 
fermentative process which induced coagulation. 

But not only were the results of this experiment in harmony with the view 
that the Bacterium lactis was the real fermentative agent: they would, as 
I believed, afford indisputable evidence of the truth of the theory, provided it 
should turn out, as former experience made me feel sure would be the case, 
that every glass which had curdled contained the bacterium, and that every 
one which remained fluid contained none. Though, as I have said, I did not 
doubt that this was the state of the case, yet I went through the laborious process 
of examining the contents of all the sixteen glasses just before leaving Edin- 
burgh, nine days after the time of the inoculation. All those which had coagu- 
lated still contained an unaltered white curd with a glistening upper surface, 
and nothing to indicate the supervention of any change secondary to that of 
the lactic fermentation. The air in the glass shade of each had the odour of 


374 ON THE LACTIC FERMENTATION 


souring, the taste of a little portion of the curd removed for investigation was 
sour and its reaction sharply acid, and under the microscope, in every instance, 
bacteria with the characters of Bacterium lactis were found, but no other organ- 
ism. And in the case of the remaining five glasses, where the milk was still 
fluid and unchanged in appearance, the air in the glass shade had merely the 
slight odour of suet, which Pasteur long since pointed out as resulting from 
oxidation ; the taste was that of fresh milk, and the reaction showed the peculiar 
form of neutrality which fresh milk exhibits, both blue and red litmus paper 
acquiring an intermediate purple tint." And on subjecting the contents of 
each to microscopic examination, I could discover under a protracted search 
no organisms of any kind. I have brought before the Society one of these last 
glasses (still under the protection of its glass cap and shade) to show that even 
after the lapse of nearly four months the milk remains fluid and unaltered. 
I need hardly say that it required considerable care to bring these glasses from 
Edinburgh without having their contents spilled. Nevertheless this is one 
which was successfully transported ; and I have placed under one of the micro- 
scopes a drop of its milk, in which it will be seen that there are no organisms 
present, and that the only alteration discoverable is that some of the milk 
globules have assumed an angular form as the result of evaporation. 

Here, again, is one of the glasses which underwent the lactic fermentation, 
and its appearance is in truth as remarkable as that of the other. We know 
that if curdled milk is kept under ordinary circumstances it soon loses its original 
characters. The Ozdiwm lactis grows upon its surface, the Penicillium glaucum 
or some other common mould probably shows itself, and the curd acquires first 
a cheesy and then a putrid smell, accompanied with great alterations of its 
aspect. Here, however, the lactic fermentation having occurred single and 
alone, we have a pure white curd to this hour, as if the milk had curdled yester- 
day, and any little smell which there is in the air of the glass shade is a slight 
sour odour.” 


* Neutral urine presents this same reaction. 

* For the sake of any one desiring to repeat this experiment, it may be well for me to add a few 
matters of important detail. The estimate of the number of bacteria present in the milk should be 
made within about twenty-four hours of the inoculation of the glass with a purified needle-point dipped 
into milk souring with the pure ferment, and then applied to the milk which is to be inoculated, close 
to the edge of the glass, as distinguished from the central part, from which the drop will be afterwards 
taken. At ordinary temperatures the bacteria will then be found about the period referred to of full 
size and isolated, and therefore easily counted ; whereas if too long a time is allowed to pass after inocu- 
lation, they will be found too numerous to be easily counted, and often of small size and in groups com- 
posed of an indefinite number. Further, if the bacteria are counted in one drop of the milk, and another 
drop is taken for dilution and inoculation, two great inconveniences will result. First, there will be 
no security that the two drops contained the same proportions of bacteria; and, in the second place, 
the knowledge that the bacteria are in process of multiplication with great speed (doubling their numbers 
in about an hour) leads to most undesirable hurry in the microscopic examination and the subsequent 


AND ITS BEARINGS ON PATHOLOGY a7 


And now let me dwell for a few minutes on the inference to be drawn from 
these facts. We have seen that boiled water rendered infective by the admixture 
of a small quantity of milk undergoing the lactic fermentation, having been 
introduced in drops of equal size into ten glasses of pure boiled milk, five of those 
glasses underwent the lactic fermentation, characterized by souring and curdling, 
while five remained altogether unaffected. This proves that the same truth 
holds regarding the lactic ferment which we have before established with respect 
to the various ferments that occur in ordinary water, viz. that it is not a material 
soluble in water, but consists of insoluble particles. For had it been dissolved 
in the water of inoculation, every equal-sized inoculating drop would have 
produced the same fermentative effect. Next we have to consider the bearing 
of our facts on the nature of those insoluble particles, the question being whether 
they were the bacteria or consisted of some so-called chemical ferment destitute 
of life, of which the bacteria were a mere accidental concomitant. Let us 
assume, for the sake of argument, that it is possible for insoluble particles to 
exist devoid of vitality, yet capable of multiplying lke the bacteria. Such 
a notion is unsupported, I believe, by a tittle of scientific evidence ; but, for 
the sake of argument, let us fora moment assume it. We should then be further 
obliged to suppose, in order to account for our facts, that these hypothetical 
particles, though merely accidental accompaniments of the bacteria, were 
present in precisely the same numbers, a thing which is utterly inconceivable. 
But we should have to go further and suppose, what is equally inconceivable, 
that these bodies of different natures, though mere accidental concomitants 
were not only exactly equally numerous, but invariably accompanied each 
other in pairs ; so that when a bacterium was introduced into one of the glasses, 
it was always associated with a particle of the hypothetical true ferment, and 
whenever the bacterium was excluded, the hypothetical ferment likewise failed 
to enter. Hence, as the only other possible interpretation of our facts involves 
what is utterly inconceivable, I venture to think that those facts will be admitted 


calculation, besides leaving uncertainty as to the estimate, in consequence of the development that is 
proceeding in the milk in the glass. But these difficulties are entirely got over by adding a minim of 
the milk to ten minims of boiled water in a purified glass, and using this first dilution both for the estima- 
tion of the bacteria and for furnishing the drop to be diluted for the purpose of inoculation. The milk 
having been well mixed with the water, the bacteria are pretty equally distributed through it, while 
the addition of so much water to the milk greatly retards the development of the bacteria and makes 
hurry unnecessary. Thus, I ascertained in one instance that the rate of increase in some milk so diluted 
and still kept protected in a pure glass appeared to have been only such as to treble the number ot 
bacteria in sixteen hours, whereas they would probably have been multiplied fourfold in two hours 
if the milk had remained undiluted. The dilution has the further advantage that it does away entirely 
with the difficulty caused by the milk globules and molecules in the recognition of the bacteria in un- 
diluted milk, even when in very thin layer. In counting the bacteria I found it convenient to take 
all the fields in succession both in the horizontal and in the vertical diameter of the covering glass, which 
with my microscope gave about a hundred fields from which to estimate the average. 


376 ON THE LACTIC FERMENTATION 


by all to afford a conclusive demonstration that the particular species of bacterium 
which we have been studying is really the cause of this special fermentation.’ 

It is true that this proof applies only to one particular kind of fermentative 
change. But the same method will, I believe, be found applicable in other 
instances for the purpose of ascertaining how far the rule is universal that 
a true fermentation, by which I mean one characterized by the faculty of self- 
multiplication of the ferment, is caused by the development of an organism. 
In the meantime, as a contribution of a definite character, so far as it goes, to 
the elucidation of the nature of fermentative changes, so fraught with interest 
at the present day alike to the physician and the surgeon, I trust it will be not 
considered unwelcome to the Pathological Society. 

There are some other points which came out in the course of this inquiry 
to which I should like to allude. One of these has reference to the cause of 
the odour of souring milk. In the lactic fermentation the sugar of milk is 
resolved into lactic acid by a mere rearrangement of its constituent atoms, 
one atom of sugar of milk going to form four atoms of lactic acid, without gain 
or loss. Now the chemist tells us that lactic acid is non-volatile, and accord- 
ingly this acid in the pure condition is absolutely odourless. Why, then, should 
souring milk have any odour? In fact this investigation has proved, as a result 
of isolating the true lactic ferment, that the smell of souring milk is principally 
due to the products of some other concomitant fermentation or fermentations. 
For when a glass of pure milk is made to sour under the influence of the Bacterium 
lactis pure and unmixed, the odour that results is extremely trifling. Neverthe- 
less the air in the glass shade over a vessel containing milk in such circumstances 
has a shght sharp odour ; and it seemed worth while to ferment a considerable 
quantity of milk in this way and subject it to distillation, so as to ascertain, 
if possible, the nature of the odorous ingredient. Having curdled boiled milk 
in a purified flask by means of pure Bacterium lactis, I mixed six ounces of the 
recently formed clot with five ounces of distilled water, and having introduced 
it into a retort, heated it for some hours in a bath of boiling water, the distillate 
being collected in a receiver kept cool with cloths over which cold water con- 


* Strictly speaking, the expression should be, not ‘ the cause’, but ‘ the cause under ordinary cir- 
cumstances’. For our facts do not of course exclude the possibility of the existence of some other 
ferment which might produce the same effect upon milk if the circumstances were favourable to its 
development, as, for example, by the exclusion of the Bacterium lactis. In truth, I once obtained as 
the result of taking milk directly from the cow into a purified vessel, a minute moving bacterium, which, 
though it developed very slowly in comparison with the Bacterium lactis, produced in time a sour curd, 
which I have little doubt was due to the change of milk-sugar into lactic acid. But thus interpreted, 
the terms in the text may be considered admissible ; just as we speak of the yeast plant as the cause 
of the alcoholic fermentation, although we know that the Mucor vacemosus, when growing unmixed in 
a saccharine solution, gives rise to the same fermentative change. 


AND ITS BEARINGS ON PATHOLOGY 377 


stantly streamed. The product, which by that time amounted to 54 drachms 
of clear watery liquid, had the sharp odour of the clot, but in a more concen- 
trated form. It was collected in three successive portions, the last of which 
had comparatively little of the sharp smell, and rather an odour like that of 
bread. That which first came off had such a sharply piercing smell that I felt 
no doubt that it was acid. To my surprise, however, I found it not only taste- 
less, but neutral to test-paper. I redistilled the product, and stopping the 
process when half had passed over, found the second distillate still more sharp 
in odour that the first, while the residue was almost odourless. But on distilling 
a third time I got a result less pungent than that of the second process, in con- 
sequence, I presume, of loss of some of the ingredient through extreme volatility. 
I kept the last distillate in a stoppered bottle for two days, at the end of which 
time it still retained its peculiar odour. What the nature of this substance 
is remains to be determined. It seems likely that it may be some ethereal 
product with the remarkable peculiarity of having an acid smell, though taste- 
less and neutral in reaction. 

It has been ascertained by Pasteur that the alcoholic fermentation, which, 
as we all know, consists in the main of the resolution of sugar into alcohol and 
carbonic acid without gain or loss of atoms, is attended with the appearance 
of other products in small quantity, such as glycerine and succinic acid, and 
the ethereal substance in souring milk may, perhaps, be related to the lactic 
fermentation in a similar manner. I cannot but think it likely that these 
apparently secondary products may, in reality, be of primary importance in 
the production of fermentative changes. Pasteur has shown that if yeast is 
added to a saccharine solution adapted for the nutrition of the Torula Cerevisiae, 
and the liquid is exposed in a thin layer in a shallow vessel to the atmosphere, 
the torula develops with peculiar rapidity, but little alcoholic fermentation 
results ; and, on the contrary, when the liquid is placed in a deep vessel in 
considerable mass, the torula develops comparatively slowly but gives rise to 
abundant fermentation. And he explains this remarkable result by supposing 
that the fungus requires oxygen for its nutrition, and when it cannot obtain 
it otherwise, abstracts it from the sugar, and so occasions the fermentation ; 
but when it can get the needful oxygen readily from the air, as it is able to do 
in the shallow vessel, it thrives peculiarly well, but, not having occasion to 
withdraw oxygen from the sugar, leaves it undisturbed, except the comparatively 
small portions of it which it assimilates for its own growth.? 


* Monsieur Pasteur expressed this view in 1861 in a Bulletin de la Societe Chimique, where, after 
relating the facts referred to in the text, he thus expresses himself :—‘ I] parait dés lors naturel d’ad- 
mettre que, lorsque la leviire est ferment, agissant a l’abri de lair, elle prend de l’oxygéne au sucre et 
que c’est la Vorigine de son caractére de ferment.’ In his recent work, Etudes sur la Biéve, 1876, M. 


378 ON THE LACTIC FERMENTATION 


The fact is certainly of extreme interest, because it seems to show that the 
breaking up of the sugar is not due to the mere presence of the growing organism 
in its vicinity ; otherwise the fermentation would be proportioned to the growth 
of the torula, and would therefore be more abundant in the shallow vessel. 
But the explanation of the difference of the results, as dependent on the necessity 
or otherwise of abstraction of oxygen from the sugar by the torula, seems to 
lack applicability without some addition to the hypothesis. For sugar does 
not lose any oxygen at all in being converted into alcohol and carbonic acid, 
and therefore the withdrawal of that element would be incompatible with the 
new arrangement of the atoms in a saccharine molecule. 

On the other hand, if we compare the formulae of glycerine and succinic 
acid with that of sugar, we see that the abstraction of an atom of oxygen from 
each of several atoms of grape-sugar might naturally lead to the simultaneous 
formation of the less complex atoms of the other substances out of the residual 
constituents of the sugar; the formation of the succinic acid involving the 
liberation of a certain amount of hydrogen, which again is required for the 
production of the glycerine: and further, that the relative proportions by 
weight in which the new compounds would be formed would be those in 
which they were actually found to present themselves by Pasteur in alcoholic 
fermentation." 

Thus the formation of the glycerine and succinic acid seems to be exactly 
explained by Pasteur’s theory of the deoxidizing agency of the torula upon 
sugar. But in order to account for the disruption at the same time of a very 


Pasteur quotes these first expressions of his theory, and adds that they ‘ n’ont rien perdu de leur rigueur ; 
bien au contraire, le temps les a consacrés ’ (op. cit., p. 257). When stating his present opinion he employs, 
it is true, terms which might seem capable of a different interpretation, viz.: ‘La fermentation par 
la levare s’est présentée 4 nous comme la conséquence directe d’un travail de nutrition, d’assimilation, 
de vie en un mot, effectuée sans gaz oxygéne libre. La chaleur consommeée par ce travail a da étre 
nécessairement empruntée de la matiére fermentescible, c’est-a-dire au corps sucré, qui, 4 la maniére 
des corps explosifs, dégage de la chaleur par sa décomposition.’ The latter of these sentences might 
seem to have no necessary reference to the question of abstraction of oxygen from sugar by the plant ; 
but it is immediately succeeded by the following: ‘La fermentation par la levire semble donc liée 
essentiellement a la propriété que posséde cette petite plante cellulaire de respirer, en quelque sorte, 
avec l’oxygéne combiné au sucre.’ Here the original theory is plainly restated, and we are led to infer 
that the decompositions of the sugar referred to in the former sentence as providing the necessary heat 
for the work of nutrition result from its deoxidation. 

* According to Miller’s Elements of Chemistry, the formulae of the three substances are—Glucose 
(i.e. grape-sugar), C,H,,O,; Glycerine, C,H,O,; Succinic acid, C,H,O,. Therefore, 5 atoms of glucose, 
less 5 of oxygen, are equal to 10 atoms of glycerine, less 10 of hydrogen ; and 2 atoms of glucose, less 
2 of oxygen, are equal to 3 of succinic acid, plus 10 of hydrogen. Therefore, 7 atoms of glucose, less 
7 of oxygen, leave the elements necessary for producing 10 atoms of glycerine and 3 of succinic acid. 
Now, the atomic weight of glycerine multiplied by 10 is 1860, and the atomic weight of succinic acid 
multiplied by 3 is 354, so that the weight of glycerine formed would be between five and six times the 
weight of succinic acid; and this is just about the proportion of the quantities of the two materials 
obtained by Pasteur from fermented sugar (see Miller’s Chemistry, vol. il, p. 161). 


AND ITS BEARINGS ON PATHOLOGY 379 


much larger number of other sugary particles into alcohol and carbonic acid, 
it would seem necessary to assume further that the decomposition of some 
atoms of glucose into glycerine and succinic acid, under the deoxidizing agency 
of the torula, exercises a disturbing influence upon neighbouring particles and 
leads to their becoming broken up into simpler compounds without loss of 
atoms. Such a theory of the alcoholic fermentation of sugar would be a com- 
bination of the views of Pasteur and of Liebig; and while assigning with the 
former authority the primary and essential place to the growing organism, 
would admit with the latter a catalytic influence exerted by decomposing organic 
substances upon unstable compounds in their vicinity. And if this be the true 
state of the case, it will be seen that the glycerine and succinic acid, though 
produced in comparatively small quantity, so far from being secondary and 
unimportant, are in fact the primary effect of the action of the torula upon 
the sugar, of which the formation of alcohol and carbonic acid is a secondary, 
though simultaneous, result. And it is considerations such as these which seem 
to me to invest with special interest the occurrence of the odoriferous ethereal 
product above referred to as an accompaniment of the pure lactic fermentation. 

This theory of the alcoholic fermentation has the advantage that its prin- 
ciple is applicable not only to cases in which the organisms concerned thrive, 
like the Torula Cerevisiae, in the presence of free oxygen, and may be therefore 
supposed to be ready to take that element from fermentable materials when they 
cannot get it in the free condition,’ but also to fermentations like the butyric, 
where, as M. Pasteur himself has shown, the long and actively moving bacteria 
which appear to constitute the ferment, instead of thriving in free oxygen, are 
rendered incapable of development by it, if not deprived of vitality altogether.? 
There seems no reason for supposing that an organism upon which oxygen in 
the uncombined condition operates as a poison, should be specially disposed to 
abstract that element from its combinations. We have in fact, here, the con- 
verse of the conditions of the Torula Cerevisiae. But nothing is more natural 
than that such a bacterium, when growing at the expense of an organic material, 
should take for the purposes of its nutrition some of the atoms composing that 
substance and leave the rest to form new combinations ; and the decomposi- 
tions arising in this manner may operate with catalytic effect upon neighbouring 

* Another well-known instance of this is presented by the common mould, Mucor vacemosus, which, 
when growing at the surface of a saccharine solution, produces little or no alcoholic fermentation, but 
brings about that change in very considerable amount when compelled to grow below the surface where 
but little free oxygen is at its disposal. M. Pasteur has also demonstrated that even Penicillium glaucum 
and Aspergillus glaucus have the same effect, though in a much more limited degree, when placed in 
similar circumstances. (Vide “tudes sur la Biére.) 


* To use M. Pasteur’s own words, the atmosphere acts upon them with ‘influence mortel/e’; the 
italics are the author’s (/:tudes sur la Biére, p. 293). 


380 ON THE LACTIC FERMENTATION 


particles, whether of the same body or of some other unstable compound present 
in the solution. For, according to this view, it by no means follows that the 
substance which is the main subject of a fermentation must be that on which 
the ferment primarily acts, or indeed, that it should contribute at all to the 
nutrition of the growing organism. Thus, so far as I am aware, it is, in the 
present state of our knowledge, an open question whether in the case of the 
lactic fermentation, as it occurs in milk, the Bacteriwm lactis may not derive 
its nourishment exclusively from the caseine, the decomposition of which may 
act catalytically upon the milk-sugar. In that case the old view of the caseine 
being the ferment would have so much of truth in it that, though not the primary 
fermenting agent, it would occupy the position of an intermediary between the 
organism and the material which undergoes fermentation. 

In the more typical fermentations, such as the alcoholic and the lactic, 
the most characteristic and striking phenomenon is the catalysis or breaking 
up of an organic substance into simpler compounds out of all proportion to 
what is required for the purposes of the nutrition of the fermentative organism : 
but it would surely be a great mistake to restrict the term fermentation to cases 
like these. The only safe ground for us to take is, I believe, to regard as 
fermentative all chemical changes brought about by growing organisms in 
the media which they inhabit, whether those changes correspond or not 
with the immediate necessities of the organism. Thus the mouldy smell 
produced by the growth of Penicillium glaucum in paste or preserve is proof of 
the formation of some volatile product at the expense of the material in which 
the fungus is growing. The chemical change thus indicated must, I conceive, 
be grouped with the true fermentations, whether the penicillium does or does 
not cause more organic particles to be decomposed than actually contribute 
to its nutrition. And in like manner I should regard putrefaction as a fer- 
mentation without reference to the question whether the amount of albumen 
decomposed is or is not more than is required for the growth of the putrefactive 
bacteria. It is nevertheless desirable to give some distinctive appellation to 
fermentations such as the alcoholic and the lactic, in which the breaking up of 
the fermentable material occurs out of all proportion to the requirements of the 
organism concerned ; and for such cases I would venture to suggest the designa- 
tion catalytic fermentations. For certain it is that catalysis, or breaking up of 
organic substances into simpler compounds, without loss or gain of atoms, does 
take place in those fermentations, whether in the manner above suggested or 
otherwise ;* so that the proposed term would express an ascertained truth, 
independently of any theory. 


* Liebig threw out the suggestion that the yeast plant may by its growth produce a material capable 


AND ITS BEARINGS ON PATHOLOGY 381 


The lactic fermentation, then, resembles the alcoholic in being a typical 
catalytic fermentation, the milk-sugar being broken up into lactic acid without 
loss or gain of atoms, while the simultaneous appearance of another product in 
small quantity presents another feature of similarity. A further point of 
apparent analogy between these two fermentations has been brought out by 
the investigation which forms the subject of this communication. In the 
experiment of inoculating ten glasses of pure boiled milk with drops calculated 
each to contain on the average a single Bacterium lactis * five of the glasses 
were capped liqueur-glasses such as have been above described, but the other 
five were in the form of test-tubes with suitable caps, employed in order 
that I might be able to transport them to London without spilling the milk. 
The milk was in about the same quantity in the two sets of vessels; but the 
test-tubes being narrower than the liqueur-glasses, the contained milk in the 
former had about twice the depth and a considerably smaller free surface, 
affording much less opportunity for the access of the atmosphere to the milk. 
The result was a very marked difference in the times of coagulation of the milk 
in the two sets of glasses; that in the test-tubes, where clotting took place at 
all, being solid within three and a half days of the time of inoculation ; whereas 
the milk remained fluid in all the liqueur-glasses till about twelve hours later, 
and in some of those glasses which ultimately curdled the change did not occur 
till nearly twenty-four hours after it had taken place in the test-tubes. Or in 
other words, assuming that the curdling of the milk implied the formation of 
a certain amount of lactic acid, it appeared that the more free exposure to the 
air in the liqueur-glasses had exercised a retarding influence upon the lactic 
fermentation in them. The facts, therefore, reminded me of Pasteur’s observa- 
tions as to the effect of atmospheric exposure in checking the alcoholic fermenta- 
tion. In the time that has passed between the delivery of this communication 
and its publication I have made an attempt to verify the observation, and also 
to ascertain whether the analogy with the corresponding fact in the alcoholic 
fermentation was real or only apparent. Tor oxygen might be conceived to retard 
the lactic fermentation in either of two ways : either on the same principle as in 
the alcoholic fermentation, by supplying an element necessary for the nutrition 
of the organism, and so preventing the operation of its deoxidizing agency, 
with attendant catalysis, or on the totally opposite principle of the free oxygen 


of acting upon sugar in the same manner as emulsin acts upon amygdalin, one of the most beautiful 
examples of pure catalysis known to chemists. Pasteur alludes to this suggestion in his work above 
referred to (Etudes sur la Biére, p. 315) as conceding the point for which Pasteur has always contended, 
viz. that the organism is the primary and essential fermentative agent. And though it seems hardly 
called for in the case of alcoholic fermentation in presence of Pasteur’s facts, yet it seems not at all 
improbable that the principle may be found to apply to some of the catalytic fermentations. 


TESee P1375; 


382 ON THE LACTIC FERMENTATION 


operating upon the Bactertwm lactis as a poison or sedative, as it has been shown 
to act on the bacterium of the butyric fermentation. The inquiry has assumed 
larger proportions than I had anticipated: but I may briefly mention here some 
of the facts ascertained. I found that when I imitated Pasteur’s experiment 
with the fermenting saccharine solution and exposed milk from a dairy in a thin 
layer to the atmosphere with arrangements for avoiding evaporation, the souring 
of the milk was retarded to a much greater degree than I had observed it in 
the comparatively thick layer in the liqueur-glasses of the former experiment. 
This effect became still more marked when oxygen was substituted for 
atmospheric air: but the unexpected fact was also elicited that carbonic-acid 
gas is still more potent than oxygen in retarding the lactic fermentation. The 
relations which these gases bear to the growth of the Bactertum lactis must be 
reserved for future consideration. 

I have introduced into this diagram a representation of the Torula Cerevisiae 
side by side with the Bacterium lactis, drawn on the same scale enlarged from 
camera-lucida sketches (the sketches are reproduced on their original scale in 
Plate XIV, Figs. a to 12). My object in so doing is to bring out the remarkable 
contrast between them in point of magnitude. This is especially striking if we 
compare the Torula Cerevisiae with the Bacter1um lactis as it was found after 
growing for three days in milk diluted with 1200 parts of boiled water (Fig. 11). 
Here they have assumed a condition so minute that the individuals of every 
pair do not equal in size the smaller granules of the torula. Being motionless, 
I could hardly have recognized them as bacteria except from their mode of 
grouping and the circumstances under which they occurred. Yet Bacteriwm 
lactis they undoubtedly were, and one such barely visible granule introduced 
into a gallon of uncontaminated milk would lead within three days to its con- 
version into a solid mass. It is a ferment just as potent as the torula in spite 
of its extreme minuteness ; and this circumstance, it seems to me, has an inter- 
esting bearing upon pathology. For it cannot be said to be an unlikely thing 
that other organisms may exist as much smaller than the Bacterrwm lactis as 
that bacterium is than the torula. But if this be the case, such organisms 
must be entirely beyond the range of human vision aided by the best micro- 
scopes that we possess. Seeing, then, that the hypothesis which I make cannot 
be regarded as extravagant, it will not do for us to say, because we cannot see 
under the microscope any organisms in a given infective liquid, that they cer- 
tainly do not exist, and that therefore we must abandon the idea to which 
analogy might otherwise lead us, that the virus concerned may be of the nature 
of an organism. We see, I say, from the comparison of these two sketches, 
that it is far from being impossible that there may exist ultra-microscopic 


AND ITS BEARINGS ON PATHOLOGY 383 


organisms as real, as distinct in structure, and as potent in their effects, as is 
the Bacterium lactis. 

But while we have thus reason to think it not unlikely that ultra-micro- 
scopic fermentative organisms may exist, we have no grounds whatever for 
believing that bacteria visible under the microscope have ultra-microscopic 
germs. The sole reason for the frequently expressed opinion, I may almost 
say axiomatic assumption, to that effect is, I believe, the fact that while ordinary 
water has been shown to cause the development of bacteria when introduced 
into organic liquids even in small quantity, yet no bacteria can be discovered 
in it by aid of the microscope. But we are apt to forget how extremely difficult 
it is, with the very high magnifying powers which it is needful to use, to discover 
such minute objects as bacteria unless they are present in large numbers. Now, 
if we recall the experiments above related of inoculating milk with very minute 
drops of water,’ we see that in the sample of ordinary tap-water examined there 
could not be more than about one particle capable of producing a bacterium 
in every I-100th minim. A drop of that size, small as it is, would, if placed 
between two flat plates of glass for microscopic examination, spread itself over 
a space about half a square inch in area, and we might search such a drop for 
an entire day without finding an individual bacterium contained in it. I once 
took the trouble to try whether I could find the Bacterrum lactis in some milk 
diluted with boiled water to the degree requisite to produce on the average 
one full-sized individual to every hundredth of a minim, but failed to do so 
with a protracted search. But the difficulty would have been immeasurably 
increased if the bacterium had resided for three days in the water and had 
acquired the characters represented in Plate XIV, Fig. 11, so minute and in- 
definite that an individual, if placed fairly in the field of the microscope, would 
probably not attract attention at all, or if it did so, would be passed over as of 
uncertain nature. In this connexion I may mention a hitherto unpublished 
observation which I made five years ago. I introduced some tap-water into 
three capped liqueur-glasses, purified by heat, and placed under glass shades. 
After a week had elapsed, on taking the glasses into a dark room and examining 
the water, with a candle placed on the other side of the vessel (a very good way 
of detecting the first appearances of nebulosity produced in a transparent fluid 
by bacteric development), I could just discern upon the free surface a delicate 
bluish film, which, on microscopic examination, proved to be composed of 
closely packed motionless bacteria of various forms, and for the most part of 
extreme minuteness. This explained an appearance which had before puzzled 
me, viz. that when water had been left undisturbed in a wine-glass for a day 


Wrelle [Sy sto 


384 ON THE LACTIC FERMENTATION 


or two, minute bacteria had shown themselves in a drop withdrawn from it, 
and applied between the immersion lens and the glass that covered the object. 
Along with the drop I had, no doubt, taken a portion of a bacteric film on the 
surface. Adult bacteria, therefore, do, as a matter of fact, exist, though it 
may be in a very minute condition, as a scum on still water, and there can, 
therefore, be no reasonable doubt that they exist also disseminated through 
moving water, but detached from one another by the motion of the liquid, 
so as no longer to present the recognizable characters which they have, even 
though extremely minute, when packed together in the form of a scum.t. And 
supposing them present, thus minute, motionless, and isolated, and as widely 
scattered as our experiments proved them to be in the water investigated, any 
attempt to search for them with the microscope would be, I do not hesitate to 
say, absolutely hopeless. 

Our morphological knowledge is also opposed to the idea that bacteria 
should have germs related in point of magnitude to the adult organism as the 
seeds of a poppy or the spores of a fern are to the full-grown plant. It is true 
that there are some species of bacteria in which appearances have been seen 
that appear to indicate the existence of spores, notably in the case of the Bacillus 
anthracis, which seems to constitute the virus of malignant pustule.2 But in 
all such cases the supposed spore or germ is not only conspicuous from its highly 


* The minute form in which the Bacterium lactis was found in milk much diluted with water is 
only an extreme degree of what was seen under other circumstances. It has been before mentioned 
(p. 374) that as the souring of milk proceeds the bacteria assume a smaller size. Also when growing 
in urine, though they presented in the early days the same dimensions as in milk, they were found much 
smaller at a later period, though still proved by experiment to retain the property of inducing the lactic 
fermentation in milk. Again, the Bacterium lactis which has been described as growing slowly in 
Pasteur’s solution at the expense of a little piece of curd, was almost as small as that in the milk diluted 
with water. The puny character of the progeny depends probably upon unsuitable or inadequate 
supply of nutritious material ; and in comparison with the media in which bacteria ordinarily thrive, 
the elements for their nutrition are extremely scanty in water. Again, as regards moving bacteria, 
it is a very common thing to see them become, not only of smaller size, but motionless as they continue to 
develop in one and the same medium. A good example of this in a bacterium of unusual form is given 
in the paper in the Microscopical Journal before referred to (p. 17 and Plate XIX; p. 321 and Plate XI 
of this volume). Itis, therefore, not surprising that moving bacteria should, asa rule, acquire motionless 
as well as minute characters in water. At the same time it is easy to understand that some particular 
bacteric species, like multitudes of algae and infusoria, may have water as their favourite habitat, and 
attain in it their largest dimensions. 

* See especially a memoir recently published in the Quarterly Microscopical Journal (vol. xvili, new 
ser.), by Dr. Ewart, who has observed that the highly refracting bodies which form in the threads that 
constitute the organism become free and afterwards multiply by segmentation, and that the individuals 
which result from this fissiparous proliferation again give origin to threads. M. Pasteur describes highly 
refracting spots, which he believes to be of the nature of germs, in some other bacteria (Etudes sur la 
Biére, p. 295); and I have myself seen what I have regarded as nuclei in the finely granular protoplasmic 
mass of some large bacteria, and I have sometimes observed the threads cleared of granular material, 
as if the nuclei were on the point of becoming free, appearances corresponding so far to those in the 
Bacillus anthracts. 


AND iS BEARINGS ON PATHOLOGY 385 


refracting character, but attains dimensions about equal to the transverse 
diameter of the thread in which it grows. 

Nor have we any right to assume that because some kinds of bacteria have 
germs, the same must necessarily be the case with all. A priovz there would 
seem to be no organisms known to us in nature with less necessity for such 
a provision. They constitute, in fact, in the adult form,a reproductive apparatus; 
perpetually multiplying with amazing rapidity by fissiparous generation. And 
further, it seems very likely that bacteria, differing widely as they do in their 
characters, may spring from various sources. I have, on several occasions, seen 
appearances which make me think that some bacteria take their origin as seg- 
ments of the threads of minute filamentous fungi. Certain it is that some such 
free segments or gemmae, as they are termed by the fungologist, have morpho- 
logical characters absolutely undistinguishable from some bacteria.’ And, 
supposing any bacteria to have such an origin, we may be pretty sure they 
would not possess germs, seeing that gemmae are themselves a form of germ 
of the fungi that produce them. In the same way there are ciliated monads 
which a few years ago would have been unhesitatingly regarded as definite 
species, but which are now well known to be the spores of various algae and 
fungi; while there are others which have been proved to be adult organisms 
with special reproductive arrangements.” 

The method of investigation which has been described in this communica- 
tion affords the opportunity of judging regarding any kind of bacterium con- 
tained in a particular liquid, whether in reality germs are present as well as 
the adult form. For if we find that the number of fermentative particles corre- 
sponds exactly with the number of adult bacteria which we have counted, we 
may infer that there were no free germs present in the liquid. Thus we may 
fairly suppose that the Bacteriwm lactis exists in souring milk only in the bacteric 
form in which we see it, although it is, of course, possible that it may form germs 
under other circumstances. Meanwhile the facts which I have adduced will, 
I hope, remove the mystery attendant on the notion that water teems with 
ultra-microscopic or invisible germs of the bacteria which we see of larger or 
smaller dimensions in organic liquids undergoing fermentative changes. 

1 See Trans. of Royal Soc. of Edinb., loc. cit., and Quarterly Journal of Microscopical Science, loc. cit. 
2 See the beautiful researches of Dallinger and Drysdale on the life-history of the Monads, Monthiy 


Microscopical Journal, August 1, and December 1, 1873; January 1, March 1, and December 1, 1874; 
and May 1, 1875. 


LISTER I Gc 


DESCRIPTION, OF PLALE 2ay 


Figs. 1 to 8 represent of natural size certain glasses of unboiled milk described in the text. They are 
examples of the alterations in appearance produced in milk by various different organisms other 
than the Bacterium lactis. From sketches taken October 1, 1877. 


Figs. 9 to 12, camera-lucida sketches, by Mr. Lister, of Bacterium lactis and Torula Cerevisiae on the 
same scale, viz. magnified 1125 diameters. 


For further description, see the plate and the text. 


Plate XIV 


BACTERIUM LACTIS 


& 
3 
2 8 
® 
xs 
id 


2S 


In eurdled Milk 
after 3 days 


In unboiled Urine 
after 2 days. 


In Milk diluted 
Fig ll. 


with 1200 parts of Water. 
after 3 days. 


e x ‘ 2) A> 
ie > £ 
fs ” ° ae « ¢ “aa 
ons Me , ~ " \ * 
Se2 Ft On? 
\ . 
‘ - 
es Ay 
Ss 1: 
%, ye" 
1% 
Ff 
ne 
Citi 4 4 Scale n Jen theusandihs of an rer. 


ON THE RELATIONS OF MICRO-ORGANISMS 
TO DISEASE 


An Address delivered before the Pathological Section of the British Medical Association 


at Cambridge, August 12, 1880. 


[Quarterly Journal of Microscopical Science, April 1881.] 


THE relation of micro-organisms to disease is a subject of vast extent and 
importance. If we compare the present state of knowledge regarding it with 
that of twenty years ago, we are astonished at the progress which has been 
made in the interval. At that time bacteria were little more than scientific 
curiosities ; whether they were animal or vegetable few people knew or cared, 
but most regarded them as animals on account of the active movements which 
they often exhibited. That they were causes of putrefaction, or other fermenta- 
tive changes, was a thing scarcely thought of; and the notion that they had 
special relations to disease would have been regarded as the wildest of specula- 
tions.._ Now, however, a mass of information has been accumulated regarding 
all these points, of which it would be hopeless for me to attempt to give even 
a brief sketch in the time at my disposal, and all that I can do is to present 
to the pathological section a few examples illustrating the progress which is 
being made in this department of research. 

First, I will mention some examples of the labours of Dr. Koch, of Woll- 
stein, in Germany. Though a hard-worked general practitioner, Koch has 
contrived to devote an immense amount of time and energy to his investiga- 
tions ; and by a combination of well-planned experiments, ingenious methods 
of staining bacteria out of proportion to the tissues among which they lie, 
a beautiful adaptation of optical principles to render the coloured objects dis- 
cernible by the human eye, and, further, by a most successful application of 
micro-photography, he has succeeded in demonstrating the presence of these 
minute organisms in a manner never before attained. 

The Bacillus anthracis is now universally recognized among pathologists as the 
cause of splenic fever, so fatal among cattle in this and other countries and capable 
of being communicated to various other animals, and, among the rest, to the 

’ The bacterium of splenic fever (anthrax) was seen and described by Rayer and Davaine as early 
as 1850; but little was done during the next ten years towards establishing the true relations between 
the micro-organism and the disease. See Recherches expevimentales sur la Maladie Charbonneuse, par 
H. Toussaint. Paris: Asselin & Cie. 

Cee 


388 ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 


human species, as has been lately illustrated by the so-called ‘ woolsorters’ 
disease’, in the North of England. The Bacillus anthracis is a large form of 
bacterium, as is shown in the accompanying woodcut, a. It is there repre- 
sented magnified 700 diameters, along with the outlines of some red blood- 
corpuscles of a mouse, and the rods of which it is composed are seen to be in 
diameter nearly one fourth of that of the red corpuscles. Koch’s method of 
staining sections shows in the most beautiful manner that these bacilli are not 
only present in the spleen and some other organs, but that they people the 
blood in the minute vessels of all parts. Koch has thus added to our conviction 
that the bacillus is the cause of the symptoms, seeing that, as he remarks, it is 


S80 


impossible to suppose that an organism can develop in such enormous numbers 
at the expense of the vital fluid without exerting a serious influence upon the 
system. . 

But the most striking and important results of Koch’s methods of investiga- 
tion are those which relate to organisms of much smaller dimensions. He found 
that, if putrid liquid is injected under the skin of a mouse, the animal may 
die in the course of a short time, as the result of the chemically toxic effects of 
the products of putrefaction absorbed into the circulation ; but, if it survive 
this primary disorder, it may succumb in the course of about two days to blood 
disease. If the point of a lancet be dipped into the blood of the heart of a mouse 


which has died in this way, and a scratch be made in the skin of a healthy mouse 
with the envenomed instrument, the second mouse dies with similar symptoms 
to those of the first, the poison being absolutely certain in its virulent operation ; 
and the same thing may be continued indefinitely through any series of animals. 
If now sections of the tissues be made and stained and examined by Koch’s pro- 
cedures, it is found that the entire blood of the diseased animal is peopled with 
bacteria, resembling those of the Bacillus anthracis in the enormous multitudes in 
which they are produced, and also in their rod-like form, but differing from them 
in being exquisitely minute and delicate, as is shown in } (drawn on the same 


ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 389 


scale as a, as is indicated by the accompanying outlines of red corpuscles), 
where it is seen that the diameter can only be represented by a slender streak 
not one-eighth of the diameter of the Bacillus anthracis, and such as, before 
the introduction of Koch’s method, would have escaped notice altogether. 
Now, this disease is totally distinct from pyaemia, being not accompanied with 
multiple abscesses or embolism; and thus it has been shown by Koch that 
septicaemia may exist as a deadly blood disease, caused by the development 
of micro-organisms, equally distinct from pyaemia and from the chemically 
toxic effects of septie products. 

On some occasions, as the result of the introduction of putrid fluid under 
the mouse’s skin, Koch found, besides septicaemia, a local affection of the seat 
of inoculation, in the form of spreading gangrene ; and, on investigating the part, 
he discovered in it, exactly corresponding with the extent of the local affection, 
another organism very differently formed from that of the septicaemia, viz. a 
micrococcus, consisting of minute spherical granules arranged in linear series, 
like strings of exquisitely minute beads, as represented at c, which is magnified 


hike a and 6 700 diameters. Believing that this locally developing organism 
must be the cause of the gangrene, he tried to separate it from the bacillus of 
the septicaemia, and succeeded through an accidental observation of great 
interest. Having till that time employed the house mouse in his experiments, 
he happened to try the inoculation of a field mouse. This animal, though so 
closely allied, proved not susceptible of the septicaemia. The bacillus of that 
disease was unable to grow in the blood of the field mouse; but the micro- 
coccus of the gangrene could develop among its tissues. The new organism 
was thus obtained in an isolated form, and, when now inoculated into the house 
mouse, produced in that animal gangrene pure and simple, extending for an 
indefinite period among its tissues. 

Thus the animal body, which had previously been an obscure field of labour 
in this department, in which the pathologist did little more than grope in the 
dark, was converted by Koch into a pure cultivating apparatus, in which the 
growth and effects of the micro-organisms of various infective diseases could be 
studied with the utmost simplicity and precision. 

One more example I must take from Koch’s work. On one occasion, as 
the result of inoculating putrid liquid into a rabbit, he observed a spreading 


390 ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 


inflammation having all the clinical characters of erysipelas ; and, on examining 
stained sections of the part, he discovered another exquisitely delicate bacillus 
resembling the micrococcus of the gangrene in being local in its development, 
while its exact correspondence in extent with that of the disease led fairly to the 
conclusion that it constituted the materies morbi.* 

I will next refer to a disease occasioned by a micro-organism discovered 
by the eminent pathologist, Professor Toussaint, of Toulouse, whom I am proud 
to see present in this Section to-day. This disease has been somewhat inappro- 
priately termed Choléva des poules, or fowl-cholera, for it is not attended with 
diarrhoea or any other of the symptoms of cholera; but, as it happened to be 
extremely destructive among the poultry-yards of Paris at the same time that 
an epidemic of cholera was raging in the city, the disorder which prevailed 
among the fowls was also given the name of cholera. The lesions by which 
it is chiefly characterized are great swelling of the chains of lymphatic glands 
in the vicinity of the trachea, pericarditis accompanied with great effusion, 
and congestion, and it may be ulceration, of the mucous membrane of the 
duodenum. It is a blood disease, and highly infectious. If some of the blood 
of a chicken that has died of it be mixed with the oats with which healthy 
chickens are fed, a considerable proportion, perhaps four out of six, are affected 
and die; and similar results are produced by mixing the intestinal excreta of 
diseased fowls with the food. It is an interesting question how the virus thus 
administered enters the circulation. The invariable affection of the lymphatic 
glands of the throat suggests to M. Toussaint the idea that some accidental 
abrasion of the epithelium in the mouth or pharynx is probably the channel ; 
and this view is confirmed by the fact that a similar affection of the lymphatic 
glands, together with other symptoms of the disease, is produced by inoculating 
the chicken in the mouth ; and further, by the circumstance that such chickens 
as fail to take the disease when fed with the infected food are lable to it when 
inoculated, implying that it was merely some accidental circumstance which 
secured their previous immunity. This disease has been made the subject of 
special investigation by M. Pasteur. He found that the micro-organism could 
be readily cultivated outside the body of the fowl. It was, indeed, somewhat 
particular as regards the fluid in which it would grow; thus yeast-water, in 
which the Bacillus anthracis grows readily, proved an unsuitable medium for 
this organism, but it grew luxuriantly in chicken broth, and, indeed, in infusion 
of other kinds of meat; but chicken broth proved peculiarly convenient for 
the purpose. M. Pasteur has been so kind as to send me some tubes in which 


1 See Untersuchungen tiber die Astiologie der Wundinfectionskvankheiten, von Dr. Robert Koch 
Leipzig, 1878. A translation of this work has been issued by the Sydenham Society. 


ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 301 


the organism has been cultivated, and a drop of the liquid has been placed under 
a microscope on the table. It will be seen that the organism is a minute form 
of bacterium, oval-shaped, tending to multiplication by transverse constriction, 
and very frequently seen in pairs, and occasionally in chains. Its transverse 
diameter is from I-50,oooth to I-25,oooth of an inch, so that it resembles very 
closely the Bactertum lactis. The woodcut d represents a camera-lucida sketch 
of the organism sent by M. Pasteur. It is drawn on the same scale as the other 
illustrations of this paper. So far as I am aware, this is the first time this 
bacterium has been shown in this country. Now, it was found by Pasteur 
that the organism could be produced in chicken broth in any number of suc- 
cessive cultivations, and to the last retained its full virulence, so that, if a healthy 
chicken was inoculated with it, the fatal disease was produced as surely as by 
inoculation with the blood of a fowl that had died of the complaint. This was 
pretty conclusive evidence that the organism was the cause of the disease, and 
that it constituted the true infective element ; because any other material that 


might be supposed to accompany it in the blood of the diseased animal must 
have been got rid of by the successive cultivations in chicken broth. 

The growth of the organism occasions no putrefaction in the liquid; so 
that this is a good example of a bacterium which is most destructive as a disease, 
but which is at the same time entirely destitute of septic property, in the primi- 
tive sense of that term as equivalent to putrefactive. After the bacterium 
has grown for a certain time in a given portion of chicken broth, it ceases to 
develop further ; and when this is the case, although the broth has lost only 
a very small proportion of its substance by weight, and although, as aforesaid, 
it has not undergone putrefaction, and still constitutes an excellent pabulum 
for ordinary forms of bacteria, the bacterium of the fowl-cholera, though intro- 
duced from some new source, is incapable of growing in it. This fact seems 
highly suggestive of an analogy with the effects of vaccination, or those of an 
attack of measles or scarlatina, in securing immunity from the disease for the 
future. Here we have a certain medium invaded by a virus capable of self- 
multiplication, as is the case with those diseases in the animal body ; the medium 
itself little affected chemically by the growth of the virus within it, but never- 
theless rendered unfit for the development of that virus for the future. But 
something more than the suggestion of analogy with vaccination has been 


392 ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 


effected by M. Pasteur. By cultivating this bacterium in a particular manner, 
which he has not yet published,’ he enfeebles the organism, as he believes, and 
produces such an alteration in it that, when inoculated into a healthy fowl, 
it produces only a modified, and no longer fatal form of the complaint ; but 
the bird is thereby rendered secure against taking the ordinary form of the 
disease. It has been really vaccinated, if we adopt M. Pasteur’s extension of 
the term vaccination to other similar cases; for just as we speak of an iron 
milestone, we may, if we please, apply the term vaccination to the use of a virus 
other than the vaccine obtained from a heifer. But though the vaccination 
with the modified bacteria of the fowl-cholera does not occasion the fatal disease, 
it produces pretty severe local effects. If inoculated on the breast of the fowl, 
it causes a limited gangrene of the pectoral muscle, the affected part falling 
off in due time as a dry slough. Through the great kindness of M. Pasteur, 
I have now the opportunity of showing to the Section a hen which has been 
treated in this way. You observe a slough on the breast of the bird about as 
Yarge as a penny piece; it is dry, and obviously old. The fowl has been some 
days in my possession subsequently to its journey from Paris; but though 
more than enough time has elapsed since the inoculation to have caused its 
death, had the disease been in the ordinary form, it is, you see, in good health, 
bright and active, and it both eats and sleeps well.” 

I will now return to the Bacillus anthracis, with regard to which I shall 
have again to refer to the labours of M. Toussaint. First, however, I must 
allude to the work of some of my own countrymen. In March 1878, an experi- 
ment was made at the Brown Institution, at the suggestion of Dr. Burdon 
Sanderson, of inoculating a calf with the blood of a guinea-pig which had died 
of splenic fever, which is exceedingly fatal to rodentia. The result was that the 
calf took the disease, but in a mild form, and recovered from it; and a similar 
fact was observed in two heifers treated in the same way.?* 

This line of inquiry has since been followed up by Dr. Sanderson’s successor 
at the Brown Institution, Dr. Greenfield, with a view of ascertaining whether 
the milder form of the disease in cattle, resulting from inoculation with the 
blood of rodentia affected with it, confers upon the cattle immunity from the 
complaint in its fatal form; or, to use again M. Pasteur’s expression, whether 
the cattle have been vaccinated with reference to anthrax. And I have great 
pleasure in being able to inform the Section, by Dr. Greenfield’s permission, 


* For an account of M. Pasteur’s method of procedure see the notes at the end of this address. 

* M. Pasteur’s researches on this subject are related in the Comptes Rendus de l’ Academie des Sciences, 
February, April, and May, 1880. 

* See ‘ Report on Experiments on Anthrax’, by Dr. Sanderson (Journal of the Royal Agricultural 
Society of England, vol. xvi, s.s., part i). 


ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 303 


that the question has been answered in the affirmative ; and that one bovine 
animal, inoculated seven months ago with virus from a rodent, has proved itself, 
on repeated inoculations, entirely incapable of contracting splenic fever, remain- 
ing free from either constitutional or local manifestations of it. 

And now to return to M. Toussaint, who has made observations with regard 
to this same subject of vaccination against anthrax fraught with the very 
deepest interest. The question arises with regard to effective vaccination, 
using the term in Pasteur’s general sense: Is it essential that micro-organisms 
should develop in the blood of the animal in which immunity from further 
attacks of the disease is to be secured? Or is it possible that the necessary 
influence upon the system may be exerted by merely chemical products of the 
growth of that organism in some other medium ? With the view of approaching 
the solution of this question, M. Toussaint has performed experiments of inject- 
ing into the blood of healthy sheep blood taken from an animal affected with 
splenic fever, but deprived of the Bacillus anthracis. Taking blood from a 
sheep just on the point of death, when the bacillus has presumably produced 
all its possible effect upon the vital fluid, M. Toussaint proceeds to deprive it 
of the living bacillus in either of two ways—by filtration, or by destroying the 
vitality of the organism. The former he effects by mixing the blood with three 
or four parts of water, and then passing it through about twelve layers of ordinary 
filter-paper. The bacillus, in consequence of its large dimensions, is entirely 
retained by this form of filter, as is proved by the fact that the filtrate no longer 
gives rise to the organism in a cultivating liquid or in a living animal. Never- 
theless, if injected in considerable quantity into the circulation of a healthy 
sheep, it produces a true vaccinating influence, that is to say, secures immunity 
from splenic fever. But, what is further extremely interesting, in order that 
this change in the constitution of the sheep may be brought about, the lapse 
of a certain time is essential. If a vaccinated sheep be inoculated with anthrax 
within a few days of the operation, it will die of splenic fever; but if from 
twelve to fifteen days be allowed to elapse, complete immunity is found to have 
been produced. Similar results followed from the injection of anthrax blood 
treated by M. Toussaint’s other method, which consists of maintaining it for 
a considerable time at a temperature of 55° C. (131° Fahr.), which has the effect 
of killing the bacillus ; after which one-half per cent. of carbolic acid is added, 
to prevent putrefaction of the liquid. The blood treated in this way having 
been proved to be free from living bacilli by negative results of an experiment 
upon a rodent, about four cubic centimetres are injected into the venous system 
of a sheep, with the effect of producing the same protective influence against 
splenic fever as is ensured by the filtered blood. These experiments are still 


394 ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 


in progress; but M. Toussaint informs me that he has already ascertained the 
existence of immunity against anthrax for three months and a half in both the 
sheep and the dog treated in this way. 

I need hardly remark on the surpassing importance of researches such as 
these. No one can say but that, if the British Medical Association should 
meet at Cambridge again ten years hence, some one may be able to record the 
discovery of the appropriate vaccine for measles, scarlet fever, and other acute 
specific diseases of the human subject. But even should nothing more be 
effected than what seems to be already on the point of attainment—the means 
of securing poultry from death by fowl-cholera, and cattle from the terribly 
destructive splenic fever—it must be admitted that we have here an instance of 
a most valuable result from the much-reviled vivisection. 

I have yet one more example to give of researches in this domain of patho- 
logy ; and this also has reference to the Bacillus anthracis. The investigator 
in this instance is Dr. Buchner, assistant physician in Munich. It is well known 
that the Bacillus anthracis is morphologically identical with an organism fre- 
quently met with in infusion of hay, which may be termed hay-bacillus. Such 
being the case, it occurred to Dr. Buchner that they might be merely one and 
the same organism modified by circumstances. For my own part, I am quite 
prepared to hear of such modifying influence being exerted upon bacteria, 
having made the observation several years ago that, when the Bacterium lactis 
had been cultivated for some time in unboiled urine, it proved but a feeble 
lactic ferment when introduced again into milk. Its power of producing the 
lactic fermentation had been impaired by residence in the new medium. In the 
case before us, indeed, the physiological difference between the two organisms 
seems, at first sight, so great as to forbid the idea of anything other than a 
specific difference. The Bacillus anthracis refuses to grow in hay-infusion, in 
which the hay-bacillus thrives with the utmost luxuriance; and conversely, 
the hay-bacillus is utterly incapable of growing in the blood of a living animal, 
whether introduced in small or in large quantities. The hay-bacillus is remark- 
able for its power of resistance to high temperatures, which is not the case with 
the Bacillus anthracis. The latter is destroyed by a very slight acidity of the 
liquid of cultivation, or by any considerable degree of alkalinity, whereas the 
former survives under such conditions. Both will grow in diluted extract of 
meat, but their mode of growth differs greatly. The hay-bacillus multiplies 
rapidly, and forms a dry and wrinkled skin upon the surface, while the Bacillus 
anthyacis produces a delicate cloud at the bottom of the vessel, increasing slowly. 
Nothing daunted by these apparently essential differences, Dr. Buchner has 
laboured with indomitable perseverance, by means of experiments carried on 


ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 395 


in Professor Nageli’s laboratory, to solve the double problem of changing the 
Bacillus anthracis into hay-bacillus, and the converse. Having devised an 
ingenious apparatus by which a large reservoir of pure cultivating liquid was 
placed in communication with a cultivating vessel, so that any cultivation could 
be drawn off by simply turning a stop-cock, and further cultivating liquid 
supplied to the organisms remaining in the vessel by a mere inclination of the 
apparatus, Buchner proceeded to cultivate the isolated Bacillus anthracis in 
extract of meat for several hundred successive generations. As an early result 
of these experiments, he found that the bacillus lost its power of producing 
disease in an animal inoculated with it. Up to this point he is confirmed by 
Dr. Greenfield, who has found that, when the Bacillus anthracis is cultivated in 
aqeous humour, after about six generations it loses its infective property. Then 
as Buchner’s experiments proceeded, the appearance of the growing organism 
was found to undergo gradual modification. Instead of a cloud at the bottom 
of the vessel, a scum began to make its appearance—at first greasy-looking and 
easily broken up—constituting, so far as appearances went, an intermediate 
form between the two organisms ; and in course of time the scum became drier 
and firmer, and at length the modified Bacillus anthracis was found to be capable 
of growing in an acid hay-infusion, and to present in every respect the characters 
of the hay-bacillus. The converse feat of changing the hay-bacillus into the 
Bacillus anthracis proved very much more difficult. A great number of 
ingenious devices were adopted by Buchner, who was, nevertheless, continually 
baffled, till at last he attained success in the following manner: Having obtained 
the blood of a healthy animal under antiseptic precautions, and defibrinated it 
also antiseptically, and having arranged his apparatus so that the pure defibri- 
nated blood, which was to be the cultivating medium, should be kept in constant 
movement, continually breaking up the scum, and also keeping the red corpuscles 
in perpetual motion so as to convey oxygen to all parts of the liquid—in this 
way imitating, to a certain extent, the conditions of growth of the Bacillus 
anthracis outside the animal body, within which the hay-bacillus could not be 
got by any means to develop—he proceeded to cultivate through numerous 
successive generations. A transitional form soon made its appearance; but 
the change advanced only to a limited degree, so that further progress by this 
method became hopeless. The modified form hitherto obtained failed entirely 
to grow when injected into the blood of an animal. On the contrary, it was 
in a short time completely eliminated from the system, just like the ordinary 
hay-bacillus. It had, however, been observed by Buchner that spores had 
never been formed by the bacillus growing in the defibrinated blood ; and it 
occurred to him that, perhaps, if it were transferred to extract of meat, and 


396 ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 


induced to form spores there, the modified organism might yet grow in the 
blood of a living animal. The carrying out of this idea was crowned with 
success ; and, by injecting various different quantities of the liquid containing 
the organism into different individuals, Buchner at length succeeded, both in the 
mouse and in the rabbit, in developing true Bacillus anthracis out of the progeny 
of the hay-bacillus. When large quantities were introduced, the animals died 
rapidly from the merely chemical toxic effects of the injected liquid; but in 
some instances in which a smaller amount was injected, after the period for 
these primary effects had passed, a fatal disease supervened—attended, as in 
anthrax, with great swelling of the spleen, the blood of which was found peopled, 
as in that affection, with newly formed bacilli; and the spleens affected in this 
way were found to communicate anthrax to healthy animals, just like those of 
animals which have died of ordinary splenic fever.* 

Supposing these results to be trustworthy (and the record of them bears 
the stamp of authenticity), I need scarcely point out to a meeting like the present 
their transcendent importance as bearing upon the origin of infective diseases, 
and their modifications as exhibited in epidemics. 

I trust that these examples may suffice to convey some idea of the work 
now going on with reference to the relations of micro-organisms to disease. 


Since the above address was delivered, M. Pasteur has published the method 
by which he produces the ‘attenuation’ of the virus, or, in other words, the 
enfeeblement of the organism of fowl-cholera which fits it for securing immunity 
from the fatal form of the disease. This method consists in cultivating the 
organism, pure and unmixed, in chicken broth, to which access of air is permitted 
while dust is excluded, and simply allowing some months to elapse before it is 
employed. If the period does not amount to more than about two months, 
the organism retains its virulence little abated, but if the period is extended 
to three or four months it is found that animals inoculated with the organism 
take the disease, but have it in a milder form, and a considerable proportion 
recover ; and if the time is made still greater, as, for example, eight months, 
the organism has so far lost its potency that though chickens inoculated with 
it still go through an attack of the disease, allrecover. If the period is sufficiently 
prolonged, there comes a time when the organism is found to have lost its vitality 
altogether, so that it will no longer give rise to new development when intro- 
duced into fresh cultivating liquid. 

In considering by what agency this enfeeblement of the organism and 
ultimate extinction of its vitality was brought about under the circumstances 


* See Ueber die experimentelle Erzeugung des Milzbrandcontagiums aus den Heupilzen, von Hans 
Buchner, Munchen, 1880. 


ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 397 


referred to, it occurred to M. Pasteur that it might perhaps be the oxygen of 
the air admitted to the vessels. Oxygen is essential to the growth of the organ- 
ism, but it might, as M. Pasteur thought, be, nevertheless, in long-continued 
action upon it, a cause of weakness. With a view of testing this idea he insti- 
tuted cultivations of the bacterium in broth contained in tubes partially filled 
with the liquid, that is to say, containing a certain proportion of their volume 
of air, but sealed hermetically. The result was a growth of the organism, indi- 
cated by turbidity of the clear fluid, attaining a degree proportioned to the 
amount of air present in the tube, but coming to an end when that air was 
exhausted, so that the little organism, no longer growing throughout the liquid, 
fell to the bottom of the vessel, leaving the fluid again clear. The organism 
having now exhausted all the free oxygen, was from this time forth presumably 
protected from the influence of that element, and, in exact accordance with 
M. Pasteur’s theory, it was found that no matter how long these closed tubes 
were kept, the organism retained not only its vitality, but its full virulence, as 
tested by inoculation of healthy chickens.’ 

There can be no question as to the great importance of these facts; and 
the medical world must for ever remain deeply indebted to M. Pasteur for 
eliciting them. Doubts may, however, be entertained regarding the inter- 
pretation of the phenomena. Thus Dr. Greenfield, whose own researches have 
had special reference to the modifying influence exerted upon bacteria by the 
medium in which they grow, has thrown out the suggestion that the enfeeble- 
ment of the organism of fowl-cholera growing with free access of air may be 
due to alterations in the fluid which they inhabit rather than to the effect of 
oxygen upon them. When free access of oxygen is permitted, the organism, he 
contends, will continue to grow till all the material suitable for its nutrition is 
exhausted, and as the nutriment becomes defective the progeny will be feeble. 
At the same time this exhaustive development of the organism will be attended 
by the full measure of possible alteration in the quality of the liquid which the 
srowth of the organism can effect, and this alteration will naturally involve the 
production of substances which may exert a prejudicial influence upon the 
organism itself. On the other hand, the bacterium, when growing in a sealed 
tube with limited supply of oxygen, has its development brought to a stand 
by the exhaustion of that gas, while the organism is in full vigour and in a fluid 
but slightly changed from its original wholesome condition. It thus remains 
like a vigorous seed, ready to start into energetic growth when the conditions 
for its germination are supplied.2, The essential difference between the two 


1 See Comptes Rendus, October 26, 1880. 
2 See ‘ The Brown Lectures’, by W. S. Greenfield, M.D., &c. ; Lecture II, Lancet, January 1, 1881. 


398 ON THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 


views may be stated shortly thus: M. Pasteur regards oxygen as a slow poison 
of the bacterium; Dr. Greenfield seeks for the slow poison in the products of 
the fermentative agency of the organism. 

The time which has passed since the delivery of this address has brought 
out facts which have led M. Toussaint to take a different view of the nature 
of the liquid used in his ‘ vaccinations’ against anthrax above referred to. In 
a letter which he has had the kindness to write to me on the subject, he informs 
me that on two different occasions injections of anthrax blood treated by one 
of his methods has led to the death of the animal from anthrax; and in one 
instance, a similar injection induced a local affection which appeared to have the 
characters of malignant pustule. He has hence been led to the conclusion that 
the diseased blood treated by his methods, instead of being (as he at first believed) 
free from the living bacillus, contained the organism in an ‘ attenuated’ form. 

Thus it would appear that the observations of Pasteur, Toussaint, and 
Greenfield agree in ascribing the ‘ vaccinating’ influence to a modified form of 
the micro-organism concerned. 

Nevertheless some other observations have been made which tend to justify 
the original line of inquiry pursued by Toussaint. Chauveau has found that if 
ewes inoculated with anthrax in the last months of gestation recover from the 
disease, not only are the mothers no longer susceptible, but the lambs enjoy 
similar immunity.t’ Further, it has been ascertained by others, including Dr. 
Greenfield, that the blood and tissues of the foetus of an animal dying of anthrax 
contain no bacilli, while those of the mother swarm with them. Putting these 
two observations together we are led to the inference that while the integrity 
of the placental vessels prevents the bacilli from entering the foetal circulation, 
the foetus is so dosed with soluble products of the development of the bacilli in 
the maternal blood as to be rendered proof against the disease. 


? See Dr. Greenfield’s First ‘ Brown Lecture’, Lancet, December 18, 1880. 


AN ADDRESS ON THE RELATIONS OF MINUTE 
ORGANISMS TO INFLAMMATION 


Delivered in the Pathological Section of the International Medical Congress, August 5, 1881. 


[Tvansactions of the International Medical Congress, London, 1881.] 


Mr. PRESIDENT AND GENTLEMEN.—In opening a discussion on the subject 
of the relations of micro-organisms to disease in general at the meeting of the 
British Medical Association at Cambridge last year,’ I brought forward what 
seemed to be some established facts illustrating the connexion between minute 
organisms and certain specific disorders, both constitutional and local. I dwelt 
especially upon the admirable investigations of M. Pasteur into the Cholera 
des poules, and those of Toussaint and others into malignant pustule or anthrax, 
and the exceedingly beautiful results obtained by the experiments and methods 
of Dr. Koch. This morning we have to discuss a more limited portion of this 
great subject—namely, the relations of micro-organisms to unhealthy processes 
arising in wounds. I have the great satisfaction, gentlemen, of knowing that 
Dr. Koch is present among us, and also that, with infinite kindness, and very 
great trouble to himself, he is about to exhibit at King’s College, to a limited 
number, his methods of procedure in actual operation. It is but to a limited 
number that these demonstrations can be made, because only a very few at 
a time can see them to advantage; but I have also the great satisfaction of 
knowing that Dr. Koch will exhibit this afternoon in this room, by the magic 
lantern, photographs of sections made by himself of various diseased tissues, 
illustrating the effects of micro-organisms. These photographs will be as con- 
vincing and as satisfactory as the actual demonstration of Dr. Koch’s processes, 
because the pictures drawn by light are entirely free from those errors which 
can hardly fail to creep in as a consequence of mental bias when a sketch of 
these minute objects is made by the human hand. Permit me to return to 
Dr. Koch the thanks of this Section for his great kindness in this matter. Thus 
the Congress will have an opportunity of seeing confirmed, and indeed extended, 
the kind of evidence which I brought before the British Medical Association 
last year. 

But while I am more than ever convinced of the importance of the relations 
of micro-organisms to diseased processes in wounds, I propose this morning to 
utter what seems to me a needed note of warning against a tendency to exaggera- 
tion in this direction. This exaggeration, if such there be, is largely due to the 


PDEE Ds) 307. 


400 AN ADDRESS ON THE RELATIONS OF 


success of antiseptic treatment. If we treat our wounds by means expressly 
calculated to exclude altogether the entrance into them from first to last of 
minute organisms, not only are the specific diseases got rid of, not only do 
hospital gangrene and pyaemia, those scourges of former surgery, fly away as 
at the touch of the enchanter’s wand, to trouble us no more for ever, while 
septicaemia also vanishes, and erysipelas, though more stubborn, is robbed of 
its terrors—not only, I say, do these diseases, recognized as specific, disappear, 
but, if the treatment is properly conducted, we get rid of inflammation altogether ; 
and we see wounds that are left with their edges widely gaping, and become 
occupied by a substantial blood-clot, heal, it may be, without a particle of pus, 
a cicatrix forming beneath the superficial layers of the coagulum. Such results, 
proceeding from a mode of treatment designed especially to exclude bacteria, 
may suggest the idea that all inflammation is caused by micro-organisms, and 
that suppuration, whether acute or chronic, is always due to similar agencies. 
Gentlemen, this I believe to be a very exaggerated view of the matter, and 
a view which may tend to have a serious influence upon our practice. For 
example, if we believe that inflammations are due only to an invasion of micro- 
scopic parasites—if that is the sole cause of inflammation in every case, to 
what purpose is it to employ counter-irritation ? Counter-irritation would seem 
an absurdity under such circumstances ; and accordingly I lately read in a work 
by a most able surgeon the statement that counter-irritation may be regarded 
as a thing of the past, as something exploded. Again, in the case of those 
important diseases which we term strumous, the languid degeneration of tissue 
which we see in feeble constitutions, there is at the present time a tendency 
to look upon this as altogether of an infective nature. This also I believe to 
be an exaggerated view, and one which may injuriously affect our practice. 
If, for example, I really believe that the degenerated tissue is infected with 
an invading parasite which is the essence of the disorder, the natural inference 
will be, that if I am to resect a joint affected with strumous disease I ought to 
cut out the whole of the diseased structures ; I should not be satisfied without 
cutting away all the degenerated textures, a practice which I believe would 
often be exceedingly disadvantageous to our patients. 

Let me say a few words in the first place with regard to acute inflammation. 
Acute inflammation is certainly very often caused by the products of decom- 
position, the results of fermentation induced by the development of minute 
organisms. Of that we have abundant proof; but we have also sufficient 
evidence, as it appears to me, that inflammation is often caused otherwise— 
viz. through the nervous system ; that, in fact, the ancient principles of John 
Hunter with regard to sympathy were true principles. Let us take, for example, 


MINUTE ORGANISMS TO INFLAMMATION 401 


the case of irritation of the urethra leading to disturbance of the kidney without 
any affection of the intermediate parts: the irritation applied to the urethra, 
the effect produced upon the kidney. This I conceive can only be explained 
through the nervous system. For instance, I have seen a strong and apparently 
healthy patient on whom lithotomy had been performed go on perfectly well 
until the first occasion of the passing of urine through the urethra as the wound 
healed. He then had a violent rigor, and from that moment there was com- 
plete suppression of urine. Death occurred from uraemic poisoning, and upon 
post mortem examination I found what had apparently been previously per- 
fectly healthy kidneys affected throughout with most intense inflammatory 
congestion. That I can only explain as occurring through the nervous system, 
by virtue of nervous sympathy existing specially between one part of the urinary 
tract and another. Again, I have known a medical man affected with stricture 
pass, after an interval of many years, a bougie upon himself. The first time 
he passed water after this had taken place he felt a cutting sensation in the 
urethra, and had a violent fit of shivering. He had all the appearance of being 
likely to follow the same course as the other patient—viz. that death would 
result from uraemia. He sent for me when suppression of urine had already 
fully declared itself. I had a piece of thin macintosh cloth put under his 
back, and on this piece of macintosh cloth, between it and the loins, I had 
placed a large mass of flannel wrung out of boiling water as hot as it could be 
applied, and the macintosh cloth drawn rapidly round the body and _ fixed 
in position with a sheet pinned over it. He, a medical man, accustomed to 
observe, told me afterwards that the effect of this seemed to be like the operation 
of a charm. He experienced an immediate sense of relief, and in a very short 
time he passed water again, the kidneys resuming their functions. Inflamma- 
tory congestion, caused sympathetically by irritation in the urethra, had been 
got rid of, and that by virtue of something acting on the principle of counter- 
irritation—an irritant applied to the skin of the loins, the part of the surface 
which is most in sympathy with the kidneys. It is the same sort of sympathy 
by virtue of which the accoucheur can induce the contraction of a relaxed 
uterus by applying a cold wet towel to the hypogastrium and the vulva—the 
special sympathy which, as John Hunter pointed out, exists between an internal 
organ and the integument nearest to that organ. 

Then, to take a very simple case, let me refer to the result of tight stitches. 
I once saw in a patient, about three days after removal of the mamma, where 
the edges of the wound had been brought together by interrupted sutures 
unusually tightly applied, an inflammatory blush extending up to the collar- 
bone. I took out the stitches and watched the result ; the fiery redness faded 


LISTER I pd 


402 AN ADDRESS ON THE RELATIONS OF 


away before my eyes, and in a few minutes was almost entirely gone. That 
redness was indubitably brought about by sympathy ; the stitches acted upon 
certain nerves, and through the nervous system the inflammatory disorder was 
produced. I imagine that all physiologists will admit that determination of 
blood might be induced through the nervous system. But it is not only this 
effect that we see from tight stitches ; we see also in time oedema, and we may 
even see death of tissue from the violence of inflammatory disturbance in the 
more immediate vicinity of the stitch, though the stitch only acts directly upon 
a microscopically small portion of the tissue. 

Counter-irritation seems to be based upon a law in physiology, which 
I may take the liberty of illustrating by some simple examples. Suppose 
a fly settles upon the skin of the face: we experience an intolerable sense of 
itching ; we rub the part with the finger, and the itching disappears—a fact 
familiar to all the world. But now I find that the same effect of removing 
the sense of itching takes place if, instead of rubbing the actual spot on which 
the fly settled, I rub in a ring round it, without touching the spot at all. What 
is the interpretation of those facts? In the first place, I suppose the sense 
of itching depends upon an abnormal action of the sensory nerves of that 
particular spot on which the fly settled. By rubbing a ring in the vicinity 
I callinto play a strong action of the sensory nerves of a neighbouring part of 
the skin which is in sympathy with that part on which the fly settled, by virtue 
of the same nervous connexion through which the skin of the chest blushed 
as the result of a tight stitch. And this new nervous action occurring leads 
to the cessation of the abnormal action which was previously going on; as if 
the attention, so to speak, of the nervous system were distracted from the 
affected part. That may seem a very homely illustration; but if the inter- 
pretation is correct, it serves the purpose none the worse on that account. 
Suppose, again, we feel a sense of irritation in the Schneiderian membrane— 
a sense of irritation which, if it goes on, will relieve itself by the violent action 
of the expiratory muscles which we term sneezing; and supposing we are 
desirous that this act should not take place—it would be inconvenient, perhaps, 
that we should sneeze—if with the hand we violently rub the tip of the nose so 
as to produce a considerable sense of uneasiness there, the sneeze is prevented. 
I do not touch the part affected with the abnormal sensation, but I call into 
play a strong action of the nerves in a part which is in sympathy with it—a part 
of the same nasal organ—and by so doing I cause the previous action to cease. 
That is another simple but instructive example of physiological counter-irritation. 

Take one more instance. I was once asked to see a young woman, pre- 
viously in perfect health, who, taking her broth—‘ kail’, as the Scotch call it— 


MINUTE ORGANISMS TO INFLAMMATION 403 


very voraciously, swallowed the bud of the kail plant, and this became impacted 
in the upper part of the oesophagus. Of course she could not swallow, and 
she came to my house surgeon to be relieved. He made certain attempts, 
which were not successful, and three days after the accident I was asked to 
see her. During these three days she had remained in apparently perfect 
general health ; she had her usual florid complexion, the pulse was absolutely 
undisturbed ; the tongue, too, it so happened, was perfectly clean. But, what 
was very remarkable, she had had no sense of hunger for those three days ; 
but she had had a curious yearning sort of uneasiness in the epigastrium, induced 
by the presence of the foreign body in the oesophagus, and this abnormal sensa- 
tion, caused by the object in the oesophagus, had taken the place of hunger. 
By virtue of the sympathy existing between the oesophagus and the stomach, 
the sensation, or nervous action, which constitutes hunger had been prevented 
from occurring. I extracted the bud which was plugging her oesophagus, and 
the normal sensation of hunger soon returned. Here, then, was another example 
of physiological counter-irritation—a term which I have ventured to apply to 
cases in which the excited nervous action which the counter-irritation removes 
has not overstepped the limits (indefinite though they be) which separate health 
from disease. 

It appears, then, that it is a law of physiology that when two parts are 
nervously in sympathy with each other, if we excite a great action in the nerves 
of one we may distract action from the nerves of the other. Now this will serve to 
throw great light upon the nature of inflammation itself if we find that counter- 
irritation is really a valuable means for the treatment of inflammation. That 
such it is I will only give one or two illustrations. I once fell upon the ice with 
my knee bent, striking the knee and producing at once a severe strain and 
a severe contusion. The knee became violently inflamed, the inflammation 
being characterized by intense pain and effusion into the knee-joint. I treated 
myself by a splint to ensure rest, and hot fomentations. Every time a fresh 
hot fomentation was applied, though the heat was so great as to be painful 
to the skin of the knee, I rejoiced in it on account of the removal of the pain 
from the interior which always attended it. I remember once having a severe 
attack of sore-throat, and a mustard poultice was put on of pure mustard and 
water. The mustard, of course, caused a burning sense of uneasiness in the 
skin of the throat; but it was a delightful sensation to me, because I felt that 
while this burning uneasiness was caused to the skin, the sharp cutting pain 
of the interior of the throat was at once attacked, and gradually disappeared 
under the influence of the counter-irritant. Experiences like these in one’s 
own person have a more convincing effect than reports from the lips of patients. 


404 AN ADDRESS ON THE RELATIONS OF 


Let me give one more example, and that is the effect of the actual cautery in 
certain forms of articular disease. When I went first to Edinburgh, the thing 
that struck me most was the effect of the cautery as applied by Mr. Syme in 
certain cases of joint disease. The first instance of this which I saw was a young 
woman with an exceedingly painful affection of the shoulder-joint. It was not 
hysteria, for there was atrophy of the deltoid muscle from instinctive disuse, 
and the disease was marked by intense pain, extending to the finger-tips, instead 
of being limited to the joint, as it would be in hysteria. The pain was, at the 
same time, worse at night, depriving her almost entirely of sleep, and it was 
accompanied by other abnormal sensations. Mr. Syme applied the actual 
cautery of red-hot iron before and behind the joint, and when the patient woke 
up from the chloroform sleep the pain was gone, and never returned ; and the 
disease, which had been going on and gradually progressing for months, was 
cut short from that time, and before long she left the hospital with a well- 
developed deltoid muscle. Several cases of a similar nature happened to occur 
about that time. One was that of a young man with ‘ ulceration of cartilage’ 
in the articulations between the occiput and the atlas, and between the atlas 
and the axis. The disease caused exquisite agony, shooting down to the 
shoulders and up into the head. The patient could not raise his head from the 
pillow without supporting it with his hand ; he could not look up to the ceiling 
or turn his head at all to one side without moving his whole body Here, again, 
the pain was worse at night, and that the disease had already produced great 
effects was evident from the fact that on examining the throat with the finger 
we felt an irregular prominence of the bodies of the vertebrae in the posterior 
wall of the pharynx. Mr. Syme applied the cautery to the skin of the back of 
the neck over the upper cervical vertebrae, and though in this instance the 
abolition of pain was not immediate, but took place more gradually, this most 
formidable inflammatory disorder, which had long resisted other forms of treat- 
ment, went on steadily to complete cure; and that the cure was permanent was 
proved by his coming to the hospital some time after to introduce his bride to us.? 
Now if it be true that counter-irritation is a powerful means of treating 
inflammation, and if the explanation which I have given of the mode of the 
action of counter-irritation, as illustrated by the physiological cases, is correct, 
then I say the effect of counter-irritation in the treatment of inflammation 
throws great light upon the nature of inflammation itself, and upon the relation 
of the nervous system to it. If counter-irritation cures an inflammation by 
withdrawing nervous action from the affected part, it follows that the inflamma- 
tion so cured was maintained by an abnormal action of the nerves of the part. 


+ See also vol a; ps 373: 


—— 


a a se ee a or ee a 


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MINUTE ORGANISMS TO INFLAMMATION 405 


This conclusion is confirmed by the fact that it is in harmony with and 
elucidates the mode of operation of the most frequent cause of inflammatory 
attacks—exposure to cold. How does a chill of the surface lead to an internal 
organ becoming inflamed ? Why should a draught of cold air upon the chest 
lead to an attack of inflammation of the lungs? First, it seems clear that in 
some way or other the effect is brought about through the nervous system ; for 
the integument only is chilled, and the deeply seated internal organ suffers, 
while the same law of sympathy or nervous connexion which we have seen in 
counter-irritation applies equally here; it is the cooling of the skin nearest 
the internal organ that is most likely to cause its inflammation. And further, 
the cold sometimes ‘strikes in’ with a suddenness that conveys the idea of 
a nervous shock, and seems to preclude the hypothesis of any other agency 
than that of the nervous system. Next we have to ask what immediate effect 
does cold produce upon the nerves of the surface on which it acts? One effect 
which cold certainly does produce is to lower the activity of the nerves on which 
it operates. In this respect it is the converse of heat. It therefore seems 
natural to suppose that cold acts in causing inflammation exactly on the con- 
verse principle that heat may act in curing it ; a diminution of the action of the 
nerves of a part of the surface leading to an increased action of the nerves of 
an internal organ in sympathy with that part. And this view of the matter is 
confirmed by familiar experience. Suppose a man is liable to inflammatory 
disorder of the bowels, what is the time when he must be most careful to keep 
his coat buttoned up when he walks out into the cold air? It is immediately 
after taking a hearty dinner ; it is just at the time when there is the greatest 
amount of physiological activity of the organs liable to inflammation. When 
the nerves of the internal organ are already doing their utmost consistently 
with health, then it is that it is most likely to suffer from additional nervous 
action thrown upon it in consequence of depression of nervous activity in the 
chilled integument with which it sympathizes—exactly the contrary effect, as 
it appears to me, to that of the actual cautery, the mustard poultice, or the 
hot fomentation. 

Let me now give a single example of the influence of the nervous system 
in producing or maintaining chronic inflammation. Suppose a patient comes 
to us with chronic inflammation of the synovial bursa situated over the patella 
and its ligament—chronic housemaid’s knee. This, as we all know, is a very 
obstinate complaint, and may have resisted perfect rest, blistering, and a variety 
of other treatment. If it has existed any length of time, we find that there is 
not only effusion of fluid into the synovial sac, but inflammatory thickening 
of the surrounding tissues. Now, I find that if we make a puncture in the sac 


LISTER I Dd 5 


406 AN ADDRESS ON THE RELATIONS OF 


through the skin with a tenotome and introduce a little drainage-tube not 
bigger in calibre than a crowquill, at the same time doing this in such a way 
as to prevent the entrance of putrefaction and employing an efficient antiseptic 
dressing, we may reckon on it as a matter of certainty that the disease which 
has been previously so obstinate rapidly becomes cured. We change the dressing 
in the course of a day or two in order to shorten the tube, and at the next dress- 
ing we probably find the serous oozing has been so slight as to permit us to 
dispense with the tube altogether, and within a week or ten days the little 
puncture is healed. Meanwhile, not only is there no reaccumulation of fluid, 
but the thickening of the surrounding tissues disappears rapidly, and before 
long vanishes altogether. Let us look at the interpretation of this fact. And 
first let me remark that the treatment which so rapidly causes subsidence of 
the obstinate inflammatory disorder does not act directly upon the diseased 
synovial membrane at all. For we do not inject the antiseptic into the sac: 
all that we do is to let out the fluid and provide against reaccumulation during 
the next few days while preventing the entrance of septic material. It is, 
therefore, plain that the presence of the fluid in some way or other maintained 
the chronic inflammation. How did it do this? Not by means of micro- 
organisms, for it was clear and transparent, and contained none. Not by 
chemical irritation, as would have been the case had it contained the acrid 
products of putrefaction. Had the fluid been pus, it might have been contended 
that it might possess some slight chemically irritating property. But it was 
the bland and wholly unstimulating liquor sanguinis. We are therefore led 
safely another step, and infer that the mere mechanical presence of the fluid, 
or, in other words, the tension which it occasioned, was the efficient agent. Yet 
it is inconceivable that the inflammatory phenomena could be caused directly 
by pressure of the fluid upon the synovial surface. Synovial effusion is not as 
a matter of fact induced by mere pressure, though carried to a far greater degree 
thau the often slack collection of fluid could occasion. Or, if there be felt any 
doubt on this point, there can certainly be none with regard to the impossibility 
of the surrounding thickening being the direct effect of the pressure. We are 
therefore compelled to have recourse to the nervous system; and it is not 
difficult to understand how it is called into play, the sac being stretched by the 
accumulated fluid, and its nerves thus sufficiently stimulated to maintain the 
chronic inflammation. 

I have next to say a few words regarding suppuration. Here we have not 
only the results of antiseptic treatment favouring the idea of micro-organisms 
being its cause, but we have actual observations of such organisms present in the 
pus. Dr. Ogston, of Aberdeen, has lately made some very remarkable observa- 


MINUTE ORGANISMS TO INFLAMMATION 407 


tions to this effect.1 He has investigated by Koch’s methods a very large 
number of abscesses, and in every acute abscess which he has examined he has 
found the pus loaded with micrococci. Not only so, but, if he has an oppor- 
tunity of observing it, he finds the pyogenic membrane infiltrated with such 
organisms. There you have direct observation which seems at first sight to 
imply that the micro-organisms are the cause of the suppuration. But this 
same accurate observer has also investigated chronic abscesses in large numbers, 
and he has not found micrococci present in any; and therefore this same 
authority himself teaches us that micrococci are certainly not the sole cause 
of suppuration. And when we turn to the acute abscess, it seems to me that 
Dr. Ogston leaves us entirely without any explanation as to the origin of the 
infection in the part in which the abscess occurs. If we are to suppose that the 
micrococci are really the cause of the suppuration, we must also suppose them 
to be the cause of the inflammation which precedes it. But the inflammation 
that precedes the suppuration may be induced by some altogether accidental 
circumstance. For instance, a woman during lactation, with the mammary 
gland in a state of high physiological activity, corresponding with that of the 
digestive apparatus of a person after a hearty dinner, as before referred to, 
is disposed to ‘ take cold’ in the part; and as the result of an accidental chill 
an acute attack of inflammation may occur, threatening milk abscess. If we 
get such a case to treat in the early stages, the inflammation may never go on 
to suppuration at all; it may terminate by resolution. But if left to run its 
course it causes abscess. We can hardly suppose that the accident of exposure 
to cold could lead directly to the development of micrococci in the part. Nor, 
even if this were admitted, can we readily understand how any treatment that 
we can adopt could lead to their dispersion if they were the essential cause of 
the inflammation. And, further, there is this to be added, that if we treat 
such an abscess antiseptically, we find exactly the same results as in a chronic 
abscess. I had a case under my care lately in King’s College Hospital of a 
woman with a milk abscess of this kind, essentially acute. I opened it, and 
introduced a drainage-tube antiseptically, and there was not another drop of 
pus after the evacuation of the thick original contents—merely a serous oozing, 
and this rapidly subsided. Why did not the suppuration continue if the micro- 
cocci were the essential cause of it? I examined, along with Mr. Cheyne, some 
preparations which he was good enough to make for me, by Koch’s method, 
of the serum that came from this abscess three days after it had been opened, 
and we had to make a long search before we could discover a single group of 
micrococci. The main mass of those which, from Ogston’s observations, I 


* See British Medical Journal, March 12, 1881. 


408 AN ADDRESS ON THE RELATIONS OF 


cannot doubt were originally present, had been already almost entirely got 
rid of. No sooner had the abscess been relieved of the tension occasioned by 
the pus pent up within it (while at the same time the entrance of septic ferments 
was prevented) than the inflammation, following the natural bent of all inflam- 
mations when all causes of irritation are withdrawn, proceeded rapidly to subside, 
and the tissues of the pyogenic membrane and surrounding parts, regaining 
their normal vigour, were then able to dispose of the micrococci with which 
they were infiltrated, just as the organism disposes of ordinary bacteria of 
various kinds after they have been injected into the circulation. Surely the 
natural, if not the inevitable, interpretation of this course of events is that the 
essential cause that kept up the acute inflammation of the abscess and pre- 
vented it from subsiding, like that which maintained the chronic inflammation 
of the bursa patellae, was the tension of the accumulated fluid, and that the 
presence of the micrococci was of entirely insignificant importance. Hence 
I am disposed to regard the view which has been taken of this matter by Mr. 
Cheyne as the one most consistent with the present state of our knowledge— 
viz. that the micrococci are, so to speak, a mere accident of these acute abscesses, 
and that their introduction depends upon the system being disordered. It has 
been now abundantly established by the observations of Mr. Cheyne himself, 
as well as by those of Dr. Koch and other observers, that in the healthy state 
of the animal body there are no micro-organisms present among the tissues. 
It is certainly a marvellous thing that the animal body is able so to fence itself 
against the introduction of these minute living beings so disposed to diffuse 
themselves in organic liquids, considering the innumerable channels which seem 
so well adapted for their reception: the respiratory passages and the alimentary 
canal, with the openings of the countless ducts, cutaneous and mucous. But so 
itis. It is only in a state of unhealthiness that the ordinary forms of bacteria 
can enter the circulation and establish themselves in the organism. It would 
appear that in the healthy body even pathogenic bacteria must enter in certain 
numbers to be able to survive ; even the most virulent forms of micro-organisms 
must be introduced in a certain amount. If they are very much diluted, even 
they cannot survive in the animal body; but with regard to these ordinary 
micrococci of which we are speaking, they do not survive among our tissues 
except in a state of disorder of the system, local or general. Mr. Cheyne will, 
[I hope, have the opportunity of bringing before us some fresh facts in elucidation 
of this subject. From what he has already published! we know that by lower- 
ing the system of an animal, such as a rabbit, by the administration of phosphorus, 
he has brought about a condition in which micrococci do enter the system and 


* Tyvansactions of the Pathological Society of London, vol. xxx, p. 557- 


ee 


MINUTE ORGANISMS TO INFLAMMATION 409 


are found in multitudes in the internal organs. Mr. Cheyne’s idea, therefore, 
is that when an inflammatory attack is sufficiently severe to produce serious 
febrile disturbance, these micrococci get in, and, finding in the pus of an abscess 
a congenial soil, develop in it in abundance. 

It remains for me to say a word as to those most chronic and languid forms 
of inflammation which we term strumous. And first I have this to say, that 
chronic abscesses connected with strumous caries of the vertebrae heal com- 
pletely, as we know by experience, if we do but keep the spine sufficiently long 
at rest, and patiently persevere with thorough antiseptic care. The situation 
of the diseased part prevents the possibility of attempting its extirpation by 
operation ; but happily such treatment is not called for. The languid strumous 
abscess recovers of itself, like the acute, though much more slowly, when simi- 
larly treated, while the degenerated osseous tissue acquires again the characters 
of healthy bone. 

And, lastly, as regards strumous disease of joints, I hope to show at King’s 
College Hospital to-day the hand of a young woman who is under my treatment 
there, and illustrates the point to which I am anxious to direct your attention. 
She is a highly strumous person, who has had Pott’s disease of the spine when 
a child, and whose wrist I excised about two years ago on account of caries 
of the carpus with sinuses. She came to us this time with great swelling of the 
other wrist and drooping of the hand from its normal position with regard to 
the bones of the forearm, implying that the disease had caused considerable 
softening of the ligaments. She also suffered great pain. It was a matter of 
the utmost importance for her that I should avoid, if possible, the excision 
of this wrist also; and as the skin was unbroken I determined to try the effect 
of free antiseptic incision. On doing this I found, to my great satisfaction, 
that suppuration had not yet occurred in the degenerated tissues ; but on intro- 
ducing a sharp spoon I observed that it passed readily into the articulation 
between the carpus and the forearm and brought out granulation tissue. Already 
were the tissues of the joint in a highly disorganized state, but the languid 
inflammation had not yet induced suppuration. That night the patient slept, 
having lost the uneasiness which previously deprived her of her night’s rest, 
and we have now got the wound almost absolutely healed, while by the careful 
use of splints the position of the hand has been rectified. The swelling, too, 
has disappeared, and she bids fair to be soon added to the list of those in whom 
the hand has been rescued from excision by an early and free antiseptic incision, 
acting apparently on the same highly important principle of relief of tension. 
Here, too, you will observe, no attempt was made to extirpate all the degene- 
rated tissues. 


410 THE RELATIONS OF MINUTE ORGANISMS TO INFLAMMATION 


Two days ago we sent home a little boy who came to us with an exceedingly 
severe condition of ‘ white swelling’: gelatinous degeneration of the synovial 
membrane of the knee-joint. Sympathetically the bones also had become 
affected, and the ends of both the tibia and the femur were greatly enlarged. 
Suppuration, however, had not yet occurred. I cut down antiseptically into 
the joint on each side with great freedom, and also gouged extensively into 
the substance of the femur and tibia on the same principle as we trephine or 
gouge a chronic ostitis in the shaft of the tibia: and I have the satisfaction 
of sending that boy home with two minute superficial sores alone remaining 
unhealed, exposed in the windows of a water-glass case, with instructions to 
come once a week to be dressed till healing shall be complete. The swelling 
meanwhile is almost gone, and we may now look upon that case as one of a knee 
rescued from excision, and in a far better condition as to promise of future 
usefulness than excision could have afforded. Such a result I should not have 
thought of aiming at had I been possessed with the idea that complete extirpa- 
tion of the tissues which had suffered degeneration was essential to the cure 
of strumous disease. 

I feel, gentlemen, that pressed as we are for time, I have dealt very inade- 
quately with one branch only of the subject of our discussion. I can only hope 
that the facts which I have adduced may serve to remind some who have been 
led to entertain doubts upon the question, that, whether as regards the etiology 
or the treatment of inflammation, it would be a great mistake to disregard the 
influence of the nervous system. 


Poi TO von UME: I 


PREFACE, v. 

EDITORIAL COMMITTEE, vi. 
CHRONOLOGICAL NOTE, x. 
INTRODUCTION, xi-xliv. 


Abscess: inflammation in, kept up by tension ot | 


fluid, 408. 
Abscess, psoas: discharge from, altered by fermen- 
tative organism, 3006. 
Abscesses, acute: micrococci in (Ogston), 407. 
presence of micrococci an accident in, 408. 
Abscesses, chronic : no micrococci in(Ogston), 407. 
connected with strumous caries of vertebrae, 
heal by rest and antiseptic cure, 409. 
Acari: as carriers of Penicillium glaucum into 
covered glasses (Godlee, footnote), 354. 
Acetic acid: action of, on involuntary muscular 
THISSUG, I. 21. 
Acid, acetic. See Acetic. 
Aggregation of blood corpuscles in mammalia, 212 ; 
in frog, 213. 
not a vital process, 213. 
Air: exposure to, has no effect on coagulation of 
blood, 79, 80 (footnote). 
and growth of bacteria, 277. 
Albuminous fluid may be affected with fermenta- 
tive changes without smell, 306. 
Alcoholic fermentation. See Fermentation. 
Ammonia theory of blood coagulation: (B. W. 
Richardson’s theory), 70, 71, 72, 73, 82, 105, 
TOO; 108, ITI; 116, 132, 241. 
does not explain influence of temperature, 108. 
fallaciousness of, 108, 132. 


Anaesthesia, general (continued): 
produced by nitrous oxide followed up by ether, 
174. 
Anaesthesia, local: produced by freezing mixture 
(James Arnott), 155. 
by ether spray (B. W. Richardson), 155. 
Anaesthesia, partial: danger of (Kirk), 166. 
Anaesthetic: danger of fitful administration of 
different atmospheres, 165. 


| ANAESTHETICS (from Holmes’s System of Surgery. 


Third edition, 1883). PartI (written 1861), 135. 


| ANAESTHETICS. Part II (written 1870), 149. 


ANAESTHETICS. Part III (written 1882), 155. 
Anaesthetics: historical sketch, 135. 
H. Davy’s suggestion as to nitrous oxide gas, 135. 
use of nitrous oxide gas by H. Wells, 135. 
Morton’s introduction of ether, 135. 
Simpson’s introduction of chloroform, 136. 
Anasarcous liquid: coagulation of after emission, 
132. 
Aneurysm: coagulation of blood in, 72. 
causes of coagulation of blood in, 78. 
Aneurysm, traumatic: coagulation in wounded 
artery, 197. 
deposition of fibrine in sac, 197. 


' Aneurysm, varicose: no deposition of fibrine in 197. 


not proved by effect of vacuum in its promotion, | 


110. 
author’s experiments, 116, 117, 118, 119, 120, 
I2%s 
and effects of temperature (Richardson), 116. 
Amygdalin: action of emulsion on, 339. 
Amy] nitrite: in collapse under chloroform, 174. 
‘Anaemia of brain’ produced by unwonted eleva- 
tion of head, 173. 
Anaesthesia, discovery of, 135. 
Anaesthesia, general: by nitrous oxide gas, 135. 
by sulphuric ether, 135; Morton’s first exhibi- 
tion of method, 135. 
by chloroform, 136. 
LESt Ol, 142: 


cold water to face removes laryngeal obstruction | 


ans Sle 
idiosyncrasy as cause of death in, 152. 
discovery of, confused with that of chloroform, 
53. 
risks of vomiting under, 166. 
“zones” of (P. Bert), 170. 
LISTER I 


Anthrax: vaccination against, 392; (Burdon San- 
derson), 392; (Greenfield), 393; (Toussaint), 393. 

Antiseptic atmosphere: and treatment of wounds, 
277s 

Antiseptic treatment of wounds: based on Pas- 
teur’s germ theory, 276, 277. 

results of, 400. 

Apparatus for inoculation of boiled milk with 
water, 364 (and footnote). 

Apparatus, local: coordinating circulation in frog’s 
limb, 40, 41. 

Aqueous humour: makes dropsical effusion coagu- 
late (Schmidt), 131. 

Areola mammae: arrangement of muscular tissue 
in, TO; 

Arnott, James: freezing by mixture of ice and 
salt as local anaesthetic, 155. 

‘ Arrectores pili’, 10, 16. 

Arterial constriction: produced by position of limb, 
177, 178. ; ; a 

Arterial pressure: effect of respiration not greater 
than that of heart, 187. 

Arterial relaxation: caused by constricting band- 
age, 183. 

ARTERIES: Parts OF NERVOUS SYSTEM REGU- 
LATING CONTRACTIONS OF, 27. 

Arteries: dilatation of, after section of nerves 
from one side of spinal cord, 30; recovery of 
contractility of, after section of sciatic nerve, 


Ee 


412 


Arteries (continued) : 
30; contraction of, on irritation of cerebro- 
spinal centre, 31; method of demonstrating, 
in web of frog’s foot on irritation of spinal 
cord, 32; temporary constriction of, in frog, 
consequent on removal of brain, 33; con- 
striction of, caused by irritation of posterior 
half of cord isolated from rest, 36 ; contraction 
of, from irritation of anterior part of cord, 37 ; 
permanent dilatation of, from remov al of part 
of posterior cord supplying branches to pos- 
terior extremities, 38; permanent dilatation 
of arteries after removal of the brain and cord, 
38; contraction of, on irritation of posterior 
half of brain or anterior half of cord, 44; con- 
traction of, effected by muscular fibres of 
circular coat, 46; dilatation of, and feebleness 
of heart, 46; dilatation of, a passive phe- 
nomenon as regards parietes of vessels, 46; 
regulation of contractions of, bynervous system: 
summary of conclusions, 47 ; reflex contraction 
of pain induced by gravity, 177 ; removed from 
body, A. W. V olkmann’ s ee on, 179 
(footnote); effect of elevation of limb on, 184; 
constriction of, in web of frog’s foot causing 
pallor, 223 ; caused by application of hot water, 
224; impairment of activity of, in web of 
frog’s foot caused by irritation, 259. 
Arteritis: spontaneous gangrene from, 69. 
coagulation of blood in, 73. 
experiments on, 73, 74. 
Artery, brachial : ligature of, illustrating persistent 
vitality of tissues, 85. 
ligature for wound of (Burgess’ s case), 85. 
successful ligature of, in apparently ead limb, 
124. 
Artery, femoral: 
of, 184. 
Artery, ligatured : 
Articular disease : 
* Artificial milk.’ 
Artificial respiration. 
Arytaeno-epiglottidean folds: 
stertor, 145. 
Ascomycetous forms of fungi, 334. 
Aspergillus glaucus in milk, 363 (footnote). 
and alcoholic fermentation, 379 (footnote). 
Asphyxia: congestion of lungs in, produced by 
carbonic acid gas, 257. 
Atheromatous degeneration of vessels: 
tion of blood in, 78. 
Atmosphere: negative influence of, on coagulation 
of blood, 79, 80 (footnote). 
organic germs in, 312. 
Atmospheric air: ‘danger of prevention of access 
of, in chloroform administration, 141. 
Atmospheric dust. See Dust. 
* Attenuation’: of virus of fowl cholera: Pasteur’s 
method of, 396. 
of Bacillus anthracis (Toussaint), 398. 
Axial cylinder: of sciatic nerve, Io1. 
composition different in chemical from medullary 
sheath, Io1. 
difference in structure between cylinder and 
sheath, 102, 103. 


phenomena following ligature 


clotting of blood in, 198. 
effects of cautery on, 404. 
See Milk. 
See Respiration. 
vibration of, in 


coagula- 


Bacillus: causing inflammation having characters 
of ery sipelas ; in rabbit, 389. 
Bacillus anthracis : spores of, 384. 


INDEX TO VOLUME I 


Bacillus anthracis (continued) : 

description, 388 

causes splenic fever in animals, 388. 

causes wool-sorter’s disease in human beings, 
388. ° 

Koch’ s method of staining, 388. 

Toussaint’s researches on, 392. 

loses infective property after cultivation in 
aqueous humour, 395. 

attenuation of (Toussaint), 398. 

not found in foetus of animal dying of anthrax, 
308. 

Bacillus, hay: development of B. anthracis from 
(Buchner), 394. 

BACTERIA, NATURAL HISTORY OF, AND 
THE GERM THEORY OF FERMENTA- 
TIVE CHANGES (1873), 300. 

Bacteria: natural history of, 275, 300. 

cannot grow on mucus of healthy urethra, 275. 

Burdon Sanderson’s experiments on, 276. 

causes of putrefaction, 277. 

exposure to air and evolution of (Burdon 
Sanderson), 277. 

growth of, in urine exposed to air, 278 et seq. 

growth of, in Pasteur’s solution, 286 et seq., 326, 
330- 

originating from filamentous fungi, 288. 

of similar morphological characters may differ 
in fermentative change to which they give 
rise, 293. 

origin of, from conidia of hyphomycetous fungi, 
300. 

untrustworthiness of classification of, based on 
absolute morphological characters, 310. 

growth of, in milk, 320, 345. 

origin of, 320. 

growth of, in turnip infusion, 322. 

production of viscous fermentation in milk by, 
22%. 

modifications of, under different conditions of 
same medium, 323. 

yellow colour produced in that medium by, 323. 

variations in growth of, in turnip infusion and 
in urine, 325. 

different modes of development of, in urine, 326. 

dark pigment produced in milk by, 329; in Pas- 
teur’s solution by, 330. 

in putrefying blood, 338. 

and lactic acid fermentation, 342. 

different kinds of, 342. 

estimation of number of, in milk, 348. 

grouped into masses, more resistant to heat than 
when isolated, 358. 

numerous varieties of, 360. 

almost all thrive in milk, 360. 

fermentative changes in milk associated with, 
365. 

experiments, 365. 

two-thirds in lactic acid fermentation, 369. 

in butyric fermentation, 379. 

microscopic : no reason for believing they have 
ultra-microscopic germs, 383. 

exist as scum on still, and disseminate in moving, 
water, 384. 

changes in character, 384 (footnote). 

originating from filamentous fungi, 385. 

and toxic infection with products of putrefaction. 
Koch’s researches on, 388 

septicaemia caused by, 389. 


INDEX. TO VOLUME’! 


Bacteria (continued) : 
modifying influence of medium on (Greenfield), 


397- 
self-protective power of healthy body against, 
408. 
Bacteria, schizomycetous, 326. 
Bacterium: different behaviour of same, in milk 
and in Pasteur’s solution, 322. 
same, produces different fermentative changes 
in same medium, 333. 
and lactic acid fermentation, 347. 
author has seen only one that would not live in 
milk, 360. 
causing viscidity in milk, 366. 
Bacterium of fowl cholera: 
properties, 391. 
development of, 391. 
enfeebled by cultivation (Pasteur), 392. 
local effects of inoculation of, 392. 
Bacterium lactis, 333. 
modifications of, in milk, 310. 
in Pasteur’s solution, 315, 320, 342. 
in turnip infusion, 315, 322. 
in ‘artificial milk’, 315, 320. 
im Urine, 317, 325. 
kills other organisms, 346. 
correction of statement previously made as to 
behaviour of, in different liquids, 366. 
does not live in Pasteur’s solution, 342. 
a rare ferment as far as boiled milk is concerned, 


no putrefactive 


343: 
the cause of lactic acid fermentation in milk, 350. 
has no spores, 351. 
universal in dairies but scarce elsewhere, 361. 
characters of, 361. 
development of, in milk—boiled and unboiled, 
362. 
accidental contamination with other 
causing error in experiments, 368. 
procedure to get rid of concomitant bacteria of 
other kinds, 368. 
pure and unmixed, its behaviour in uncon- 
taminated unboiled urine, 370. 
incapable of growing in Pasteur’s solution, 371. 
suggested explanation of error in previous 
experiments as to behaviour in various liquids, 
372 (footnote). 
experimental proof that it is cause of lactic 
fermentation, 373. 
in ordinary circumstances the cause of lactic 
acid fermentation, 376. 
much smaller than Torula cerevisiae, 382. 
becomes smaller as milk sours, 384; and in urine, 
384 (footnote). 
modification of, 
urine, 394. 
Bacterium of splenic fever (anthrax) described by 
Rayer and Davaine, 387 (footnote). 
Bandage, elastic: Esmarch’s, 177, 183. 
has no effect on sensation or motor power, 183. 
Bat: dilatation of small vessels in wing of, after 
destruction of lower cervical and upper dorsal 
regions of spinal cord, 28. 
Beck, Marcus: reference to introductory lecture 
by, 186. 
Bell, C.: explanation of slight bleeding from 
contused wounds, 78. 
Berkeley: his view on derivation of yeast plant 
from filamentous form, 292. 


forms 


by cultivation in unboiled 


E.€ 


| Bernard, Claude: 


413 


effects of divisions of sympa- 
thetic nerve in neck, on blood vessels of ear 
and side of face, 27. 

his view that increased action of intestine after 
death is due to failure of circulation, 80. 
author’s experimental confirmation of this, go. 

Bert, Paul: experiments on dosage of anaesthetics, 
162; his three ‘ zones ’ and law of percentages, 
162. 

author’s control experiments on mice, 162. 

Bichloride of methylene: Paul Bert’s experiments 

on, 162; his law of percentages, 162. 
compared with chloroform, 175. 

Bickersteth: stoppage of pulse in three cases of 
amputation of thigh under anaesthesia, 138 
(footnote). 

Bladder: sometimes stimulated through cerebro- 
spinal axis, 97; paralysed by its more powerful 
action, 97. 

Blood: instance of difference between natural 
receptacles of, and ordinary matter in relation 
to, 105. 

‘determination’, and transition’ to inflamma- 
tory congestion, 231. 

Blood, asphyxial: coagulates more slowly than 
ordinary, 118. 

Blood, circulation of. See Circulation. 

Blood clot: slight tendency of, to induce coagula- 
tion, 128. 

regarded by author as living tissue with regard 
to blood, 128. 

in relation to coagulation, 193. 

extension of, outside bodies, 
footnote). 

non-extension of, in living vessels, 195. 

observations on, in horse, 195. 

shrinkage of, caused by micro-organisms, 196; 
caused by extension, 196. 

undisturbed, within healthy body will not spread, 


195 (Freund in 


197. 

disturbed, acts like wound tissue in inducing 
coagulation, 197. 

limitation of, to immediate vicinity of a wound 
in veins of stump after amputation, 197. 

Blood, coagulation of: causes of, in diseases ot 

blood-vessels, 69. 

Richardson’s theory, 70, 71, 82, 115, 132, 2413 
discussed, 132. See also Ammonia. 

in aneurysm, 72. 

in arteritis, 73. 

in phlebitis, 73. 

effects of chemical irritation of vessels on, 77. 

effects of mechanical violence on, 80 (foot- 
note). 

produced by inflammation, 83, 133. 

FURTHER RESEARCHES ON, 105. 

its non-coagulability below 40° Fahr. outside 
vessels, 106. 

rapid coagulation at high temperatures, 106. 

CROONIAN LECTURE on, 109. 

John Hunter ON, 110. 

Hewson on, 110. 

Gulliver on, I10. 

experiments on, by churning with wire, 113. 

effect of exposure to foreign solid on, I15, I19, 
P90. 22: 

effect of vacuum in promoting (Scudamore), I15 ; 
(Richardson), 115. 

experiments on, 115, 116, 117, 118. 


414 


Blood, coagulation of (continued) : 
effect of temperature on, 116. 
vital theory of, 121; experiment demonstrating, 
I2I. 
influence of contact with ordinary solids on, 127, 
128, 191; experiments on this point, 125, 126, 
128. 
neither oxygen nor rest has any influence, 132. 
summary of process, 132, 133. ; 
and inflammation, 133; experiment on this point, 
133- 
in its practical aspects, 180. 
AUTHOR’S EXPERIMENTS, IQI. 
relation of tissues to, 242. 
in vein of amputated sheep’s foot produced by 
foreign solid substances, 241. : 
takes place more slowly the later it is examined 
after death or amputation, 241 (footnote). 
See also Coagulation. 
Blood, constitution of, 109. 
Blood corpuscles. See Corpuscle. 
Blood fibrine: nature of, 1009. 
Blood, fluidity of : after death, 75; J. Hunter’s ob- 
servations on, 75. 
phenomena due to residual activity in tissues, 
70. 
continues longer in small vessels than in large, 
80, 82. 
in senile gangrene (Gillespie’s case), 80. 
in meningitis (Gairdner’s case), 80. 
in complication of medical and surgical com- 
plaints, 80; observations showing this, 80. 
persistence of, in vessels of amputated limb, 86. 
E. Briicke’s observations on, 108. 
in air-tight receptacles, 113. 
not due to active operation of living vessels, 
198. 
persists in amputated healthy limb, 241. 
Blood, healthy: no spontaneous coagulation of, 


192. 

Blood of horse: rapid subsidence of red corpuscles 
in plasma, 107; ‘sizy’ layer in, 107; experi- 
ment on coagulation of, 108, 189. 

Blood, inflammatory : buffy coat in, 216. 

Blood : influence of living vessels on, 79. 

Blood pressure : untrustworthiness of haemodyna- 
mometric tracings of, 180. 

author’s method of making blood stream write 
its own record, 180, 188. 

Leonard Landois’s method, 181 (footnote). 

systolic and diastolic, relative amounts of, 180, 
181. 

Stephen Hales’s manometrical experiment on, 
181. 

Blood: putrefactive fermentation of, 337 

no inherent tendency in, to putrefy, 33 

Blood, putrefying: organisms in, 338. 

Blood serum. See Serum. 

Blood, stagnation of: produced by local appli- 
cation of chloroform, 226; caused by local 
application of heat, 230; by mechanical irri- 
tation, 230. 

Blood in vessels has no spontaneous tendency to 
coagulate, 127; action of living membrane of 
vessels on, 127. 

Blood vessels: influence of nervous system on, 27. 

dilatation of, by stimulus due to effect on 
_ hhervous centres for arteries, 97. 
injury of, and coagulation, 122. 


> 
O 


8. 


INDEX TO 


VOLUME 7 


Blood vessels (continued) : 
walls of, deprived of vital properties cause co- 
agulation, 123. 
structures and functions of, 218. 
loss of vitality of walls of, in inflammation, 269. 

Blood-vessels of face : Waller and Budge on regula- 
tion of, by spinal cord, 28. 

Blood-vessels, large: lose vital properties sooner 
than others, 123. 

Bloodless method : Esmarch’s, 177 ; bleeding follow- 
ing itsapplication, 183; no effect on sensation 
or motor power, 183. 

Bloodlessness: production of, in arm, 176; pro- 
duced in limb by position and elastic bandage, 
177; experiment on horse, 177. 

Bowman: on contractile fibres of iris, 1; on me- 
chanism of contraction of pupil, 4; criticism 
of his views, 6. 

Brachial artery. See Artery. 

Brain: temporary constriction of arteries conse- 
quent on removal of, in frog, 33. 

Brain, ‘anaemia ’ of: caused by unwonted eleva- 
tion of head, 173. 

Brain, posterior part of : mechanical irritation of, 
followed by improvement in circulation, 93. 

galvanization of, inhibits heart (Weber), 93. 

Brain and spinal cord: permanent dilatation of 
arteries after removal of, 38. 

Bramah press: application of principle of, to 
treatment of wound of palmar arch, 186. 

Breast, abscess of: following local chill, 407. 

Breathing, obstruction of: during chloroform 
administration, 143. 

not caused by ‘falling back’ of tongue, 144. 
treatment of, 148; by dashing of cold water on 
face and chest, 148; by galvanism, 148. 

Breathing, stertorous: in chloroform anaesthesia, 
143: impossible when the tongue is pulled 
forward, 144; of two kinds: palatine and 
laryngeal, 144; vibration of arytaenic-epiglot- 
tidean folds in, 145. 

British Medical Association: experiments of Chloro- 
form Committee, 158; ethidene recommended 
by, asa substitute for chloroform, 175. 

Brown-Séquard : on elevation of local temperature 
after division of sympathetic nerve in neck, 
27. 

on increase of temperature in paralysed parts 
after transverse section of spinal cord in birds 
and mammals, 28. 

Bricke, E.: observations on the variations in 

colour of the skin of the frog, 48. 

holds that fluidity of blood in living body 
depends on action of vessels, 108 (footnote). 

his experiments on turtles, 108 (footnote). 

his experiments on coagulation of blood in 
turtles and frogs, IIT. 

inquiry into conditions determining coagulation, 
191; author’s investigations, I9I. 

Buchanan, Andrew: coagulation of hydrocele 
fluid by addition of serum of coagulated 
blood, 129, 189. 

Buchner: experimental development of Bacillus 
anthracis out of progeny of hay bacillus, 394. 

Buffy coat in inflammatory blood, Wharton Jones’s 
explanation of, 216. 

in healthy horse’s blood, 217. 

Bullae: occurring after contusion, 271; mistaken 

for gangrene, 271. 


INDEX TO VOLUME I 


Bursa patellae: chronic inflammation caused by 
introduction of drainage tube into sac, 405. 
influence of nervous system in production of in- 
flammationin, 406. 
inflammation of, kept up by tension of fluid, 406, 
408. 


Butyric fermentation. See Fermentation. 


Cadge: reduction of mortality after lithotomy 
following introduction of chloroform, 148 
(footnote). 


Capillaries: transudation of fluid from, in inflam- 
mation, 133. 
circulation in, 219. 
Capillaries of dermis: effects of irritants on, 260. 
Capillary system: agencies in, counteracting 
tendency to clotting, 199. 
Carbolic acid : efficacy of strong watery solution of, 
in destroying organisms, 278, 286 (footnote), 311. 
Carbonic acid: effect of, in producing inflamma- 
tory congestion of tissues, 257. 
congestion of lungs caused by, 271. 
Carbonic acid gas: and lactic acid fermentation, 382. 
Carbuncle: report of case in Syme’s practice 
(1854), 206. 
treatment of, 207. 
essentially a disease of true skin, 207. 
Cardiac movements: effects of irritation of vagus 
on, 92, 93+ 
See also Heart. 
Cat: contraction of pupil in, from exposure of iris 
to light after death, 8. 
Catalytic fermentation. See Fermentation. 
Cattle: production of immunity against anthrax 
in, 392. 
Cautery, actual: use of, in joint disease, 404. 
Cells, muscular fibre, 3, 15. 

Centre in cerebro-spinal axis for regulating con- 
tractions of arteries of frog’s foot, 32. 
Cerebral hemispheres: seem to play no part in 
regulating arterial contractions in feet, 44. 
Cerebro-spinal axis: nervous centre in, for regu- 

lating contraction of arteries in frog’s foot, 32, 36. 
regulates functions of cutaneous pigment cells 
in frog, 62. 
Cerebro-spinal centre: effect of irritation of, on 
arteries of frog’s foot, 31. 
effects of chloroform on, 136. 
Cervical vertebrae, upper: pain in, 
actual cautery, 404. 
Chameleon, changes in tint due to heat rays, 61 
(footnote). 
Chauveau : immunity against anthrax produced in 
ewes by inoculation transmitted to lambs, 398. 
Cheyne, Watson: fatal case of chloroform adminis- 
tration, 161. 
examination of serum from milk abscess, 407. 
micrococci an accident in acute abscesses, 408. 
no micro-organisms in healthy tissues, 408. 
lowering of system in rabbits by administration 
of phosphorus enables micrococci to enter, 408. 
inflammation producing serious febrile disturb- 
ance enables micrococci to develop in pus of 
abscess, 409. 
Chill: inflammation due_ to, 
nervous system, 405. 
inflammation of breast produced by, during 
lactation, 407. 
Chloric ether. See Chloroform. 


cured by 


caused through 


415 


Chloroform: impairs function of spinal cord in 
regulation of calibre of vessels, 224 (footnote). 
locally applied, produces stagnation of blood, 226. 
formation of rouleaux caused by application of, 
to shed blood, 215. 
increased adhesiveness of red blood corpuscles 
in body caused by local application of, 229. 
effect of local application of, on pigment cells in 
web of frog’s foot, 255. 
effect of, on cilia, 261. 
Chloroform administration : 
in, 143. 
obstruction of breathing in, 143. 
danger signals in, 143. 
necessity of attention to breathing rather than 
to pulse, 146. 
safest in horizontal position, 147, 150. 
preliminary examination of chest unnecessary 
before, 147. ; 
preparation for, 148, 171; 
longed fasting, 171. 
sickness after, 148. 
summary of rules for, 149 
mode of, in Edinburgh and Glasgow, 149. 
no special skill required, 149. 
entrusted to ‘clerks’ in Edinburgh Royal In- 
firmary, 149. 
necessity of watchfulness some time after dis- 
continuance, I5I. 
Chloroform as an anaesthetic: mechanism of its 
effects, 136. 
prevention of shock, 136. 
Chloroform (1861): Morton’s first experiment on 
himself with, 135. 
used in St. Bartholomew’s Hospital by Lawrence 
in summer of 1847, 1306. 
Simpson’s use of, 136. 
suggested as an anaesthetic to Simpson by 
Waldie, 136. 
effects of, 136. 
prevention of shock by, 136. 
not inflammable, and therefore better than ether 
in operations by artificial light, 136 (footnote). 
effect of, on pulse, 137. 
prevention of faintness during operations, 137. 
lessens chance of secondary haemorrhage, 137. 
mental tranquillity induced in patient by pros- 
pects of immunity from suffering, 137. 
still (1861) not used in many parts of Europe, 
and even of United Kingdom, 137. 
fatal cases from use of, 137. 
given about 5,000 times by Syme without a 
death, 137. 
extensively used by J. Y. Simpson without 
accident, 137. 
heart disease supposed to be a common cause of 
death under, 137. 
death from imperfect administration, 138; stop- 
page of pulse in incomplete administration of 
(Bickersteth in footnote), 138. 
death during operation in first case in which it 
was intended to use it in Edinburgh Royal 
Infirmary, 138. 
its safety in diseased heart, 1309. 
regulation of percentage in inspired air, 140. 
Snow, John, his inhaler, 140; his statistics of 
deaths under, during ten years, 142. 
administration of, with folded cloth in Edin- 
burgh, 140. 


stertorous breathing 


collapse after pro- 


416 INDEX TO 


Chloroform (continued): : 
difference of susceptibility of different animals 
to, 140 (footnote). 
overdose from too long administration cause of 
most deaths under, 142. 
careless administration accountable for deaths 
during trivial operations, 142; requisites for 
safety in giving, 142. 
author’s method of administering, 143. 
test of anaesthetic effect, 143. 
case of insusceptibility to, 143 (footnote). 
suspension of reflex action under, 143. | 
most safely given in horizontal position, 147 
(footnote). : ; , 
not applicable when assistance of patient 1s 
required, 148. 
in operations involving copious haemorrhage 
into mouth, 148. 
does not increase risk of pyaemia, 148 (footnote). 
diminished mortality after lithotomy following 
introduction of, 148 (Cadge quoted 1n footnote). 
summary of rules for its administration, 149. 
Chloroform (1870): safety of, author’s experience, 
149; Syme’s experience, 149 ; no death from, in 
Edinburgh or Glasgow Royal Infirmaries, 1861— 
70, 149. 
obstructed respiration from falling back of 
tongue under, 151. 
varieties of its effects on cerebral and spinal 
centres, 152. 
differences in relation of sensation to conscious- 
ness under, 152. 
abolition of reflex action under, 152. 
occasional cessation of thoracic movements 
under, 152. 
idiosyncrasies in relation to, 152. 
different behaviour of patients under, 152. 
eyeball reflex not unvarying indication of 
anaesthesia, 152. 
relaxation of sphincters of bowel and bladder 
under, 152. 
sighing respiration under, 152. 
failure of cardiac ganglia extremely rare, 153. 
discovery of, confused with discovery of anaes- 
thesia, 153. 
Chloroform (1882): largely superseded by ether in 
Great Britain, 155. 
action of, on heart, 157. 
effects of, on heart according to dosage (Snow), 158 
effect of, on heart and respiration, 159. 
administration still (1882) entrusted by author 
to senior students, 160. 
operations under, on patients with diseased 
hearts, 160. 
case of death under, in author’s practice, 160. 
Paul Bert’s law of percentages, 162. 
zone maniable (Paul Bert), 162. 
varying susceptibility to chloroform in different 
animals, and in the same animals at different 
times, 163. 
importance of mild but constant atmosphere in 
administration of, 165. 
danger of allowing recovery from time to time 
(Kirk), 166. 
causes after-sickness more than ether, 166. 
administration of, by means of drop bottle and 
flannel bag, 167. 
experiments as to amount and time required for 
production of anaesthesia, 170. 


VOLUME I 


Chloroform (continued) : 
applicable whenever an anaesthetic is wanted, 172. 
mixture of, with ether and alcohol, 174. 
collapse under, treated by inversion, 172. 
treated by artificial respiration, 173. 
mixture of, with ether and alcohol as a preventive, 
174. 
inhalation of nitrite of amyl, 174. 
preliminary hypodermic injection of morphia as 
a preventive of collapse, 174. 
Chloroform Committee of the British Medical 
Association : experiments of, 158. 
Chloroform and ether: their respective advantages, 


154. 
Chloroform fright: fatal case of, 161. 
Chloroform-giver: special appointment of, not 
only unnecessary but dangerous, 150. 
Chloroform mask: devised by author, 168. 
details of administration by this means, 169. 
advantages of, 171. 
Chromatoporous cells in frog’s skin, 50, 51. 
arrangement of pigment granules in, 52, 53. 
action of galvanic shock on granules, 55. 
movements of granules, 55, 56. 
physiological interest of these movements as 
instances of vital action, 56. 

functions of, under control of nervous system, 56. 

author’s experiments, 57, 58, 59. 

tendency to diffusion after liberation from con- 
trol of nervous centre, 59. 

accommodation of tint of skin to that of sur- 
rounding objects, 59. 

experiments showing this accommodation to be 
due to reflex action of light through optic 
nerves, 59, 60. 
concentration of, invariable result of action of 
nerves upon, 254. 

action of chloroform on, 255. 

effect of mechanical violence on, 255. 

effects of nervous influence on, 260. 

See also Pigmentary. 

Chyle : flow of, in mesenteric lacteals of mouse, 25. 
solid matter not absorbed by, 25. 

Cilia: effects of irritants on, 260. 
effect of chloroform on, 261. 
effects of galvanism on, 262. 
effects of heat on, 262. 

Circulation: effect on, of position of part, 176. 
stoppage of, by position and elastic bandage, 

177 ; experiment on horse, 177. 
effect of position not explained by simple 
hydraulic principles, 187. 
influence of position on, explained by vasomotor 
system, 188. 
effects of irritants on, in web of frog’s foot, 211, 
224. 
observation on cause of, 220. 
causes of, 240. 
Clarke, Lockhart: 
cord, 99. 
Clot, blood. See Blood. 
Cloth, folded: administration of chloroform with, 
140. 

Clover: ‘close’ method of administering ether, 156. 
his smaller ether inhaler, 157. 

COAGULATION OF BLOOD, FURTHER RE- 

SEARCHES ON (1859), 105. 

COAGULATION OF THE BLOOD (Croonian 

Lecture, 1863), 109. 


method of preparing spinal 


INDEX TO 


COAGULATION OF BLOOD IN ITS PRACTI- 
CAL ASPECTS (£801)5 180: 
Coagulation of blood: causes of, on diseases of 
blood-vessels, 69. 
Richardson’s theory of, 70. See also Ammonia. 
author’s observations on, 71, 72. 
experiments on, 72, 80 (footnote), 115. 
in decomposition, 81; observations on this, 
(footnote). 
in neighbourhood of tied artery, 78. 
in contused wound, 78. 
in atheromatous degeneration of arteries, 78. 
negative influence of atmosphere on, 79. 
effect of chemical irritation of vessels on, 77. 
effect of mechanical irritation on, 80. 
produced by inflammation, 83. 
induced by introduction of solid matter into 
living vessels, 106. 
John Hunter on, 110. 
Hewson on, I10. 
Gulliver on, 110. 
theories of: mechanical (rest), 110; chemical 
(exposure to air or oxygen; escape of carbonic 
acid gas; evolution of ammonia), 110, III; 
vital: influence of living vessels in preventing 
(Astley Cooper, Thackrah, Brtcke), 111. 
vital theory and ammonia theory not neces- 
sarily inconsistent, III. 
experiments with view to corroborate ammonia 
theory as applied to b'ood outside body, 
Li2. 
experiments on, by churning with wire, 113. 
effect of exposure to foreign solid on, 115. 
effect of vacuum in promoting (Scudamore), 115, 
(Richardson), 115; experiments on, 115; effect 
of temperature on, 116. 
experiments on, 116, 117, I18. 
experiment demonstrating vital theory of, 121. 
at seat of injury of blood-vessels, 122. 
caused by walls of vessels deprived of vital 
preperties, 123. 
influence of contact with solids on, 125. 
neither oxygen nor rest has any influence on, 
1323 
summary of process, 132, 133. 
and inflammation, 133 ; experiments on this point, 
133; relation of neutral liquids (Berry Hay- 
craft’s experiments), 192. 
Freund’s observations, 192. 
uninfluenced by active living tissue, 192. 
vessels injured or impaired in vitality act like 
solid, 192. 
observations on, in feet of sheep removed by 
butcher, 192. 
blood-clot in relation to, 194. 
relation of tissues to, 242. 
in veins of amputated sheep’s foot produced by 
foreign solid substances, 241. 
takes place more slowly the later it is examined 
after death or amputation, 241 (footnote). 
See also Blood. 
Coagulation of blood in horse: 
author, 108, 180. 
Coagulation of hydrocele fluid: Buchanan’s ob- 
servations on, 129, 189; author’s experiments, 
129. 
Coagulation of lymph. See Lymph. 
Coagulation of milk, 323, 349. 
Coagulum. See Blood-clot. 


SI 


experiment by 


VOLUME I 417 


Cohn, F.: his classification of bacteria, 310. 
his statement as to non-branching of certain 
organisms, 323. 
his ‘ pigment bacterium ’, 320. 
Cold: influence of, in causing inflammation, 258. 
inflammation due to, caused through nervous 
system, 405. 
effects of, on nerves of surface exposed to it, 405; 
how it acts, 405. 
need of protecting of parts in greatest physio- 
logical activity from, 405. 
inflammation of breast produced by, during 
lactation, 407. 

‘Colloidal’ matter. See Matter. 

Congestion, inflammatory. See Inflammatory. 

Congestion of lungs in asphyxia, 257. 

produced by carbonic acid gas, 271. 

Congestions, post mortem: simulating inflamma- 
tion, 84 (and footnote), 232. 

Constriction, arterial, produced by position of 
limb, 177, 178. 

Contractile tissue of iris, observations on, I. 

Cooper, Sir Astley: experiments on effect of 
mechanical injury on coagulation of blood, 
77 (footnote). 

influence of living vessels in preventing coagula- 
tion of blood, iit. 

influence of living vessels on coagulation of blood, 
LOL: 

Cord, spinal. See Spinal. 

Corpuscles, blood: adhesiveness of, in inflamed 
parts, 83. 

influence of, on coagulation, 130. 

addition of, promotes coagulability of dropsical 
effusions, 130. 

do not act as living cells in coagulation of blood 
but by virtue of chemical material which they 
contain (Schmidt), 131. 

presence of, makes liquor sanguinis spontaneously 
coagulable, 131. 

aggregation of, in inflamed part, 212. 

agglutination of, in mammals, 212. 

in frog, 213. 

in bat, 213. 

adhesiveness of, increased by gum arabic, 215. 

diminished by acetic acid, tincture of cantha- 
rides, croton oil, almond or olive oil, 215. 

unaffected by temperature, 216 (footnote). 

no effect produced by galvanic current on, 
216; 

Corpuscles, blood, red: subsidence of, producing 
pellucid appearance in vessels before coagula- 
tion, 83. 

agglutination of, in mammals, 212. 

in frog, 213. 

in bat, 213, 230. 

aggregation caused by application of salt solution 
(Wharton Jones), 226; (Fr. Schuler in 
footnote). 

increase of adhesiveness caused by 
of mustard, 228. 

caused by chloroform, 220. 

aggregation of, produced in amputated limb by 
application of mustard, 235. 

show no adhesiveness in healthy part, 236. 

adhesiveness in inflammatory congestion never 
greater than healthy blood withdrawn from 
body, 236. 

remarkable adhesiveness of, in bat, 230. 


297 


22] 


application 


418 


Corpuscles, blood, white: aggregation of, 214. 
appearance of, in irritated part, 237. 
free from adhesiveness in healthy part, 238. 
Cotton wool: sterilization of, 236 (footnote). 
Counter-irritation: erroneously regarded as ex- 
ploded, 400. 
applied to loins in suppression of urine, 401. 
physiological, 402 ; examples of, 402, 403. 
as a means of treating inflammation, 403. 
examples of its action, 403. 
in inflammation, explanation of its action, 403. 
Counting bacteria: method of, 348. j 
Crico-thyroid membrane: opening of, in respira- 
tory obstruction during chloroform adminis- 
tration, 148. 
Croonian Lecture on Coagulation of the Blood, 109. 
Curare. See Urari. 
Cutaneous pigmentary system of the frog, 48. 
Cutis anserina: KGlliker’s explanation of, 9. 
induced by artificial excitation of cutis, 12. 


Davaine: described bacterium of splenic fever, 
387 (footnote). 

Davey: observations on coagulation of blood, 75. 

Davy, Humphry: his suggestion of nitrous oxide 
gas as an anaesthetic, 135. 

Death in Edinburgh Royal Infirmary at beginning 
of first operation at which it was intended to 
use chloroform, 138. 

Death from fright when mere profession was made 
of administering chloroform (Snow), 139. 
Death under chloroform: how caused, 137; only 

case of, witnessed by author, 137; result in 
this case attributed by him to shock, 138; 
from mental emotion, 139. 
Decomposition: coagulation of blood in, 81; ob- 
servations on this, 81 (footnote). 
caused by lifeless agents, 339. 
Dentists : chloroform given by, in sitting position, 
147 (footnote). 
Dematium fuscisporum: in milk, 321. 
its bacteric nature, 321. 
a fungus allied to Dematium pullulans, 331. 
different modes of germination, 331. 
Dematium pullulans (de Bary), 321. 
Determination of blood: different from inflamma- 
tory congestion, 231. 
Detrusor: temporary paralysis of, in man, as result 
of injury, 97. 
Dichloride of ethidene more fatal than chloroform, 
175. 
Disease: relations of micro-organisms to, 387. 
Diseases of blood-vessels: causes of coagulation 
of blood in, 69. 
Diseases, zymotic, 335. 
Dropsical effusions: c 
of blood, 130. 
indistinguishable from pure liquor sanguinis, 
130. 
congealed by aqueous humour and by material 
from non-vascular part of cornea (Schmidt), 
bSi 
Dust, atmospheric: filamentous fungi and torulae 
In, 253. 
method of filtration, 354. 
prevention of entrance into glasses, 357. 
Dust: organic germs in, 312. 


oagulability of, on addition 


Ecchymosis, post mortem, 84. 


INDEX TO 


VOLUME I 


EFFECTS OF THE POSITION OF A PART ON 
THE CIRCULATION THROUGH IT (1879), 


176. 
Effusions, dropsical. See Dropsical. Fi 
Ehrenberg: reference to his classification of 


bacteria, 309. 
Ellis, G. V.: on involuntary muscular fibre, 16. 
Emulsin: action of, on amygdalin, 339. 
Epidermis: exfoliation of, after injury, 269. 
Epigastrium: examples of sympathy of oeso- 
phagus and, 403. 
Epiglottis: vibrations of, in stertor, 145. 
traction on tongue does not pull it forward, 145. 
Epiphysis, ossifying, of bone of calf’s leg, 204. 
Epes raising arms as means of stopping, 
188. 
Epithelium cells: 
268. 
Esmarch’s bloodless method in operations, 177. 
bleeding following, 183. 
Ether, chloric. See Chloroform. 
Ether (1882): chloroform largely superseded by, 
in Great Britain, 155. 
change in mode of administration, 156. 
action of, on heart, 157. 
special risks of, 157. 
close method of administering, 156. 
death caused by, from congestion of the lungs 
(Parsons), 156; from acute bronchitis, 156. 
death from failure of heart under, 158. 
death from fright, at commencement of inhala- 
tion of (Lowe, referred to in footnote), 160. 
Paul Bert’s experiments on, 162; law of per- 
centages, 162. 
causes sickness during administration more than 
chloroform, 166; deaths owing to this, 166. 
causes after-sickness less than chloroform, 166. 
administration of, preceded by nitrous oxide, 174. 
Ether and chloroform: their respective advan- 
tages, 154. 
Ether, sulphuric: Morton’s painless extraction of 
tooth under, 135. 
greater safety of, as anaesthetic (Mason Warren), 


sensitiveness of, to irritation, 


r5 3: 
Ethidene dichloride : recommended as anaesthetic 
by Chloroform Committee of British Medical 
Association, 159. 
more fatal than chloroform, 175. 
Excision of wrist: operation for, 176. 
Ewart: spores in Bacillus anthracis, 384 (footnote). 
Exostosis from os humeri removed from a young 
lady: notes of examination of, 201. 
Exudation, acute inflammatory: distinguished 
from that of dropsy by coagulability, 199. 
of liquor sanguinis in inflammation, 269. 
Eylandt: author of name ‘arrectores pili’, Io. 


Fainting fit: effect of lowering head in, 188. 

Femoral artery. See Artery. 

Ferment: self-multiplication of, the essence of 
fermentation, 339. 

Ferment, lactic: rarity of, in air, 363; scarce in 
ordinary water, 364; experimental proof of 
this, 364. 

Ferment, vesical mucus: the special ferment of, 
358. 

Fermentation, lactic acid, 341. 

FERMENTATION, THE NATURE OF (1877); 


eo 
IIDI° 


INDEX TO 


Fermentation, alcoholic: caused by yeast plant, 
339. 
of sugar, Pasteur’s explanation, 377; Liebig’s 
view, 379; theory of, 378, 379; a catalytic 
process, 381; checked by atmospheric exposure 
(Pasteur), 381. 
Fermentation, butyric: 341. 
action of bacteria in, 379. 
Fermentation, lactic acid: produced by organisms 
in milk, 324. 
in milk not produced by exposure to atmosphere, 
324. 
Miller on, 341. 
bacteria and, 342. 
produced only by Bacterium lactis, 343. 
unboiled milk not spontaneously prone to, 344. 
and Bacillus lactis, 347. 
two kinds of bacteria in, 369. 
experimental proof that it is caused by Bac- 
terium lactis, 373, 375- 
oxygen and carbonic acid gas in, 382. 
See also Lactic acid. 
Fermentation of organic liquids: due to develop- 
ment of organisms, 353. 
Fermentation, putrefactive: in wounds, 335. 
of blood, 337. 
not caused by oxygen of air, 337. 
Fermentation, viscous: produced in milk by 
bacteria, 321. 
Fermentation, catalytic, 380. 
Fermentative agency in water consists of insoluble 
particles (Burdon Sanderson), 365. 
Fermentative changes: germ theory of, 275. 
changes of putrefactive character produced in 
urine by oidium, 296. 
different, produced in same medium by same 
bacterium, 333. 
in water, associated with bacteria, 365. 
Fermentative organisms: ultra-microscopic, pos- 
sible existence of, 382. 
Ferments: prevent growth of organisms in milk, 
346. 
Ferments, chemical : 
Liebig, 339. 
Fibre, involuntary muscular. See Muscular. 
Fibre cells, muscle: in web of frog’s foot, 18. 
in intestine of pig, 18. 
measurement of, 22. 
in stomach of rabbit, 23. 
Fibrine : composition of (Schmidt), 131. 
does not exist in solution in the plasma, 189. 
composed of fibrinogen and fibrinoplastic sub- 
stance, 189. 
influence of shrinking of, on blood corpuscles, 
195. 
deposition of, in sac of traumatic aneurysm, 197. 
not deposited in varicose aneurysm, 197. 
agencies in capillary system capable of dissolving 
clotting, 199. 
Fibrinogen in liquor sanguinis, 189. 
Fibrinoplastic substance in blood corpuscles, 189. 
Filamentous fungi. See Fungi. 
Fissiparous generation in organisms, 281. 
Fluidity of blood. See Blood. 
Foster, Michael: length of period of inspiration, 
169. 
Fowl cholera: clinical characters of, 390. 
Toussaint’s observations, 390. 
Pasteur’s researches, 390. 


doctrine of, advocated by 


VOLUME I 419 


Fowl cholera (continued) : 
description of micro-organism causing, 391. 
bacterium of, has no putrefactive properties, 391. 
vaccination against, 393. 
‘attenuation ’ of virus of (Pasteur), 396. 

Freezing as a local anaesthetic: by mixture of ice 
and salt (James Arnott), 155; by ether spray 
(B. W. Richardson), 155. 

Freund (of Vienna): relation of meat liquids to 
coagulation, 192. 

Fright, death from. See Death. 

FROG, CUTANEOUS PIGMENTARY SYSTEM 
OF (1858), 48. 

Frog: increase of temperature in paralysed parts 
after transverse section of spinal cord, 28. 

effect of division of nerves on one side of spinal 
cord on arteries of lower limb, 30. 

method of demonstrating constriction of arteries 
on irritation of web of foot, 32. 

effects on vessels of removal of brain, 33. 

effects on vessels of removal of different parts 
of spinal cord, 33, 35. 

variations of calibre of vessels in web of foot on 
removal of brain, 33, 35; on removal of 
spinal cord at different levels, 34 ; on division 
of spinal cord, 35. 

nerve cells in leg producing irregular contrac- 
tions of arteries after division of brain from 
spinal cord, and amputation, 38, 39, 40, 41. 

Frog’s foot: muscular fibres in minute vessels in 
web of, 18. 

inflammatory congestion in web of, induced by 
mechanical irritation, 193. 

FUNCTIONS OF VISCERAL NERVES WITH 
SPECIAL REFERENCE TO THE S5S0O- 
CALLED ‘INHIBITORY SYSTEM’ (1858), 87 

Fungi, filamentous: in urine exposed to air, 280. 

in atmospheric dust, 283. 

bacteria in urine originating from, 288. 

development of, in milk, 363. 

different fermentative changes produced by, 363. 

most frequently found in milk kept for a con- 
siderable time (footnote), 363. 

bacteria originating from, 385. 

Fungi, hyphomecetous: different ways of germina- 
tion of, 309. 

Galvanization: of intestine (rabbit’s), effects of, 
88, 89. 

of vagus, effects on cardiac movements, 92, 93. 

effect of, on cutaneous pigmentary system, 247, 
251. 

effect of, on cilia, 262. 

Gamgee, John (New Veterinary College, Edinburgh): 
mention of, 81, 107. 

Ganglia, intrinsic: contractions of heart 
peristalsis of intestines regulated by, 97. 

Ganglionic apparatus in submucous tissue of intes- 
tine, 91. 

Gangrene, hospital: development of, 
dressings if left long unchanged, 333. 

no special virus in, 333. 
Gangrene, spontaneous : from arteritis, 69. 
Gangrene, spreading: Koch’s researches on, 389. 
micrococcus Of, 389. 

GERM THEORY OF PUTREFACTION AND 
OTHER FERMENTATIVE CHANGES AND 
THE NATURAL HISTORY OF TORULAE 
AND BACTERIA (1873), 275. 


and 


beneath 


420 INDEX TO 


Germ theory, Pasteur’s: the basis of antiseptic 
treatment of wounds, 276. 

Germ theory of putrefaction and other fermenta- 
tive changes, 275. 

Germs of bacteria, 383, 384 (footnote). 

Germs, organic: in atmosphere, 312. 

Gland, mammary. See Breast. 

‘ Glass garden’: stocking of, with filamentous fungi, 
299. 

stocking of, with bacteria, 327. 

Godlee: suggestion as to heating of milk for 
experimental purposes, 312. 

Penicillium glaucum carried by acari into covered 
glasses, 354 (footnote). 

Goodsir : demonstration of effect of heat on colour 
of chameleon, 61 (footnote). 

Graham: observations on changes from fluid to 
insoluble condition of ‘colloidal’ forms of 
matter, 120. 

diffusion of liquids a slow process, 197. 

Granuligera: cause of putrefaction in urine, 282. 
in unboiled milk, 344. 
in milk, 363. 

Greenfield, W. S.: vaccination against anthrax, 392. 
modifying influence of media upon bacteria, 397. 
blood and tissues of foetus of animal dying of 

anthrax contain no bacillus, 398. 

Gulliver: on coagulation of blood, 110. 


Hair follicles: muscles of, 11. 

Hales, Stephen: manometrical experiment on 
blood-pressure, 181. 

his experiment on force of blood-pressure in 
carotid of a horse, 187. 

Hall, Marshall: his explanation of accumulation 
of blood corpuscles in capillaries by abnormal 
adhesiveness of vascular parietes, 234. 

Harless, E.: observations on the variations in 
colour of the skin of the frog, 48. 

Hay bacillus. See Bacillus. 

Haycraft, Berry: experiments on coagulation of 
blood, 192. 

Head: depression of, in collapse under chloroform, 
172. 

Heart: feebleness of, and dilatation of arteries, 46. 

movements of, experiments on, 88. 

effects of galvanization of vagus on movements 
of" 92, 93. 

increased action of, in mammals, said to be 
caused by division of vagus (Pfliiger), 93; 
this not confirmed by author’s experiments, 93. 

action of, increased by struggling, 93. 

increased by feeble galvanic currents after 
division of both vagi, 93. 

diminished by more powerful currents, 93. 

contraction of ventricles caused by mechanical 
or chemical irritation of vagus in neck soon 
after death (Valentin), 95. 

revival of action under very powerful galvanism, 
95- 

failure of action from emotion or pain, 96. 

contractions of, regulated by independent opera- 
tion of intrinsic ganglia, 97. 

loses vital properties sooner than smaller vessels 
of viscera and superficial vessels of whatever 
size, 123; cause of this, 123, 124. 

paralysis of, causing death under chloroform 
(Snow), 140. 

action of chloroform and ether on, 157. 


VOLUME I 


Heart (continued): 
effects of chloroform on, according to dosage 
(Snow), 158. 
labour of, influenced by large varicose veins, 187. 

Heart disease: supposed to be common cause of 

death under chloroform, 137. 
safety of chloroform in, 139. 
operations under chloroform in cases of, 160. 
Heat: blood stagnation caused by local applica- 
tion of, 230. 
effect of, on cilia, 262. 
effect of, on pigment cells in web of frog’s foot, 266. 
as a means of purifying liquid contaminated with 
organisms, 358. 

Hen: vaccinated against fowl cholera by Pasteur, 

se) 

Henle: statement as to existence of muscular 
tissue in hairless parts unconfirmed, 14. 

Hernia, strangulated omental: constipation at- 
tending, 96. 

Hewson: on coagulation of blood, rio. 

Hodges (of Leicester): death from bronchitis 
caused by ether, 156. 

Hodgkin: formation of rouleaux of red blood cor- 
puscles,.212. 

Horripilation, 10. 

Hospital, old: unhealthiness not caused by new 
organisms, but by modification of those com- 
mon to it and new institutions, 333. 

Housemaid’s knee. See Knee. 

Humerus, exostosis of, removed by Syme, 201. 

Hunter, John: on coagulation of blood, 75, 110. 

observation that blood which had lain several 
days in a hydrocele coagulated spontaneously 
when let out, 132. 

his view of inflammation, 209. 

process of vesication, 269. 

inflammation caused through nervous system, 
400. ; 

sympathy between internal organ and integu- 
ment nearest to it, 401. 

Hydrocele fluid: observations on coagulation of 
(A. Buchanan), 129, 189; author’s observa- 
tions on, 120. 

indistinguishable from pure liquor sanguinis, I 30. 

Hydraulics: and practical medicine, 186. 

HYDROSTATICS, AND, HYDRAULICS, (AP- 
PLICATION OF A KNOWLEDGE OF, TO 
PRACTICAL MEDICINE (1882), 186. 

‘ Hydrostatic paradox ’, 186. 

Hyphomycetous fungi: inferior varieties of asco- 
mycetous forms, 334. 


Immunity: experimental production of, against 
anthrax (Toussaint), 393. 
against anthrax produced in ewes by inoculation 
transmitted to lambs, 398. 
Indigo: not absorbed by mesenteric lacteals in 
mouse, 25. 
INFLAMMATION, EARLY STAGES OF (1857), 
209. 
Introduction, 209. 
Section I : aggregation of corpuscles in blood, 212. 
Section II: structure and functions of blood 
vessels, 218. 
Section III : effectsof irritants on circulation, 224. 
Section IV: effects of irritants upon the tissues, 
246. 
Conclusion, 270. 


ENDEX TO’ VOLUME I 


Inflammation: nature of, elucidated by pig- 
mentary changes in frog’s skin, 65. 
an impairment of vital energies of tissues of part, 
GAS 
and coagulation of blood, 77, 133. 
coagulation of blood produced by, in vessels, 83. 
post-mortem congestion simulating, 84, 270 
(footnote). 
capillaries choked with blood corpuscles in, 133 ; 
experiments on this point, 133. 
from action of irritants on tissues, 134. 
characterized in early stage by obstruction to 
blood-flow through minute vessels, 210. 
John Hunter’s view of, 200. 
aggregation of blood corpuscles in, 212. 
influence of cold in production of, 259. 
post-mortem appearances, 270. 
distinction between result of direct irritation 
and that indirectly produced through nervous 
system, 272. 
having characters of erysipelas, caused by in- 
oculating putrid fluid into rabbit, 389. 
relation of minute organism to, 399. 
not always due to organisms, 400. 
caused through nervous system, instances of, 
401, 402. 
explanation of effect of counter irritation on, 403. 
due to cold, caused through nervous system, 405. 
Inflammation, acute: caused by products of 
decomposition, 400. 
caused through nervous system, 400. 
Inflammation, chronic: influence of nervous 
system in production or maintenance of, 405. 
Inflammation, of skin: produced by tight stitches, 
40l. 
Inflammatory congestion: cause of, 134. 
induced in web of frog’s foot by mechanical 
violence, 193. 
different from determination of blood, 231. 
post mortem, 231 (footnote). 
independent of central nervous system, 234. 
adhesiveness of blood corpuscles in, 236; never 
greater than in healthy blood withdrawn from 
body, 236. 
an instance of suspension of vital properties 
by irritants, 269. 
caused by pressure, 271. 
Inflammatory disorder of bowels, 
greatest after dinner, 405. 
Inflammatory oedema: from bites or stings, 271. 
Inflammatory process: summary of, 270. 
causes of in man, 271. 

Inhibitory action on heart of sympathetic branches 
connecting cord with cardiac ganglion, 96. 
Inhibitory influence: on intestine acts through 

mesenteric nerves, 9I. 
depends on strength of operation of some 
afferent nerve, 98. 
“Inhibitory system’ 
nerves, 87. 
Inoculation of ewes with anthrax produces im- 
munity which is transmitted to lambs, 380. 
Internal organ: sympathy between it and integu- 
ment nearest to organ, 401. 
Intestine : experiments on movements of, 88. 
inhibitory influence of galvanism acts not on 
muscular tissue but on nervous apparatus, 89. 
peristaltic action (in rabbit) increased by spinal 
galvanization, 89. 


liability to 


and functions of visceral 


A2I 


Intestine (continued) : 
peristaltic action of, continuing after death, 89. 
author’s experiments showing increased peri- 
stalsis after death to be due to failure of circula- 
tion through medium of nervous apparatus, 90. 
muscular irritability outlives co-ordinating power 
of nervous apparatus in, after death, go. 
muscular contractions of, regulated by gan- 
glionic apparatus in submucous tissues, 91. 
co-ordinating power lasts longer than inhibitory 
property in spinal system, OI. 
persistence of vermicular movement after com- 
plete division of mesenteric nerves, 91. 
increased movement of, caused by mechanical 
irritation of cord, 92. 
peristalsis of, regulated by action of intrinsic 
ganglia, 97. 
Intestine, mammalian: nerve cells in (Meissner), 
at. 
Inversion: in collapse during chloroform ad- 
ministration, 172; cases illustrating its utility, 


173. 
IRIS: OBSERVATIONS ON CONTRACTILE 
TISSUE. OF (9552); t 
KO6lliker on cellular constitution of plain muscular 
TISSUE; 1; 
structure of, in horse, 6. 
contraction of, from exposure to light, in cat 
and rabbit after death, 8. 
nerves of, 8. 
Irritant: meaning of the word, 268. 
Irritants: effects of, on tissues, 246. 
application of, produces dilatation of arteries, 
245. 
produces adhesiveness and 
corpuscles, 246. 
impairs functional activity of tissues, 248. 
effects of, on pigmentary tissue, 249. 
paralysis of nerves caused by, 250. 
temporarily impair functions of tissues, 268. 
used in gentle form act on some tissues as 
stimulants, 268. 
action of, on tissues, 269. 
Irritation: inherent power of recovery from, in 
tissues, 257. 
reaction of tissues after, 268. 
Irritation of vessels, chemical : 
coagulation of blood, 77, 82. 
illustrative specimens, 82 (footnote). 
Irritation of vessels, mechanical: effect of, on 
coagulation of blood, 80 (footnote). 
Itching: stopped by rubbing in ring around the 
part, 402. 


accumulation of 


effect of, on 


Joint disease: use of cautery in, 404. 
Joints, strumous disease of : treatment of, 400. 
Jones, Wharton: cellular structure of muscle, I. 
observations on dilatation of arteries after section 
of sciatic nerve, 28. 
effect of section of sciatic nerve in thigh of frog, 


47- ; 
effects of irritants on circulation in bat’s wing, 
2TT. 


adhesiveness of red blood corpuscles increased 
by addition of solution of gum arabic, 214. 

explanation of buffy coat in inflammatory blood, 
216. 

reference to 
(footnote). 


structure of blood vessels, 218 


422 INDEX TO 


Jones, Wharton (continued) : 
contractility of veins in mouse and bat, 222 
(footnote). : 
effect of arterial contraction in producing 
accumulation and stagnation of corpuscles in 
capillaries, 225 (footnote). og he 
adhesion of red corpuscles after application of 
salt solution, 226. 
increased adhesiveness of white corpuscles 
resulting from irritation, 237 (footnote). _ 
aggregation of red discs in vessels of bat’s wing, 
239 (footnote). 
Jugular vein. See Vein. at 
Junker’s inhaler: for chloroform administration, 
106, 167. 


Keith, Thomas: on ether as compared with chloro- 
form in ovariotomy, 154. 

Kidney: disturbance of, caused by irritation of 
urethra, 401. 

Kidneys: good effect of heat applied to back in 
inflammatory congestion of, 401. 

Kirk, of Glasgow: danger of partial anaesthesia, 166. 

Knee: inflammation of, relieved by hot fomenta- 
tions, 403. 

Knee, housemaid’s: cured by introduction of 
drainage tube into, 405. 

caused by stimulation of nervous system by 
fluid, 406. 

Knee-joint: gelatinous degeneration of synovial 
membrane of, treated by free antiseptic in- 
cision and gouging, 410. 

Koch, Robert : his work on minute organisms, 387. 
method of staining Bacillus anthracis, 388. 
experiments on toxic infection with products of 

putrefaction and diphtheria, 388. 
demonstrations of effects of organisms 
diseased tissues, 399. 

KXOlliker: his discovery of cellular constitution of 

plain muscular tissue, I. 

on muscular fibre-cells, 3, 15. 

on sphincter and dilator of pupil, 4. 

on muscular apparatus of skin, 9. 

his explanation of cutis anserina, 9. 

‘knotty swellings’ in muscular fibre-cells, 19. 

his measurements of muscular fibres in pig’s 
intestine, 21. 

his statement that fibres of nerve roots become 
smaller in passing inwards through columnar 
region, 104. 

Kupfer and Ludwig: observations that splanch- 
nic nerves lose inhibitory action some time 
after death, and acquire a motor power over 
intestine, 95. 


on 


LACTEAL FLUID, FLOW OF, IN MESENTERY 
OF MOUSE (1857), 25. 
Lacteals: experiments as to absorption of solid 
particles by, 25. 
Lactic ferment: killed by bacterium lactis and other 
ferments, 346. 
author’s method of experimenting on, 354. 
eilects produced by, in milk, 361. 
rarity of, in air, 363. 
scarce in ordinary water, 364; 
proof of this, 364. 
actic acid fermentation, in milk: produced by 
organisms, 324. 
process of, 341. 


experimental 


VOLUME I 


Lactic acid fermentation, in milk (continued) : 
Miller on, 341. 
bacteria and, 342. 
produced only by Bacterium lactis, 343. 
unboiled milk not spontaneously prone to, 344. 
and Bacterium lactis, 347. 
two kinds of bacteria in, 369. 
oxygen and, 382. 
See also Fermentation. 
LACTIC FERMENTATION AND ITS BEAR- 
INGS ON PATHOLOGY (1878), 353. 
consists of insoluble particles, 375. 
experimental proof that it is caused by Bacterium 
lactis, 373. 
caused in ordinary circumstances by Bacterium 
lactis, 370. 
caused in one instance by a different bacterium, 
376 (footnote). 
a catalytic process, 381. 
Landois, Leonard: tracing of blood stream on 
paper, 181 (footnote). 
Laryngeal obstruction in chloroform administra- 
tion, 150. 
Laryngeal stertorous breathing, 144. 
caused by vibration of mucous membrane on 
orifices of arytaenoid cartilages, 145. 
Larynx: closure of, different ways in which it may 
be caused, 146 (footnote). 
Leptothrix: filaments in urine exposed to air, 280, 
282. 
Liebig : crystallization of supersaturated solution 
of sulphate of soda, 196. 
action of emulsin on amygdalin, 339. 
advocate of doctrine of chemical ferments, 339. 
alcoholic fermentation of sugar, 379. 
catalysis in fermentation, 380 (footnote). 
LIGATURE OF BRACHIAL ARTERY ILLUS- 
TRATING PERSISTENT ViIbAbiTye On 
TISSUES (1858), 85. 
Liquor sanguinis: does not coagulate, per se 
under influence of ordinary matter, 129. 
pure, indistinguishable from dropsical effusions 
and hydrocele fluid, 130. 
its relation to inflamed tissues, 244. 
exudation of, in inflammation, 269. 
Lister, Joseph Jackson: formation of rouleaux of 
red blood corpuscles, 212. 
Lithotomy: cause of rigor on passage of urine 
through urethra, 401. 
Living tissues. See Tissues. 
Lungs, congestion of: produced by carbonic acid 
gas in asphyxia, 257, 271. 

Lymph, coagulation of: in inflamed parts, 83, 244. 
Lymph, exudation of, resulting from post-mortem 
inflammation (produced by ammonia), 83. 
Lymph: (fibrine of effused liquor sanguinis) 

coagulation of, 78, 79. 


Mackenzie, Richard: case of death after putting 
up of fractured radius without chloroform, 139. 

Malignant pustule. See Pustule. 

Mammae: arrangement of muscular tissue in 
areola of, 10. 

Mammalian circulation: effects of irritants on, 211. 

Mammary gland. See Breast. 

Marey, I. J.: his experiment on secondary arterial 
contraction, 233. 

Matter, ‘colloidal’: changes of, from soluble to 
insoluble state (Graham), 129. 


INDEX TO VOLUME I 


Matter, solid: influence of, in promoting coagula- 
tion of blood, 128. 
Mazonn, J. F.: on muscular fibre-cells, 16. 
Medico-Chirurgical Society Committee : percentage 
of chloroform by volume recommended for 
anaesthesia, 170. 
Medullary sheath: of sciatic nerve, 100. 
of spinal cord, 100. 
different in chemical composition from axial 
cylinder, IOI. 
difference in structure between sheath and 
cylinder, 102, 103. 
fibroid arrangement of, 103. 
fatty matter in, 103. 
diminution in size in fibres of nerve roots as they 
pass inwards through columnar regions, 104. 
Meissner (of Bale): nerve cells in mammalian 
intestine, 41. 
demonstration of ganglionic apparatus in sub- 
mucous tissue of intestine, 91; verified by 
author, 91. 
Membranes, serous. See Serous. 
Mental emotion: a cause of death under chloro- 
form, 139; instances (Snow; R. Mackenzie), 


130. 
Meredith : avoids vomiting from chloroform during 
ovariotomy and after-sickness by using Jun- 
ker’s inhaler, 166. 
Mesenteric nerves. See Nerves. 
Mesentery: flow of lacteal in mouse’s, 25. 
Methylene bichloride: Paul Bert’s experiments 
on, 162; his law of percentages, 162. 
compared with chloroform, 175. 
Mice, young: more tolerant of chloroform than 
adults (Snow and author), 162. 
Micrococci: in acute abscesses, 407. 
presence of, in acute abscesses in accident, 408. 
enter system in rabbits lowered by phosphorus, 
408. 
develop in pus of abscess when inflammation 
produces serious febrile disturbance, 409. 
Micrococci of suppuration: do not survive unless 
local or general disorder exists, 408. 
Micrococcus of septicaemia, 380. 
MICRO-ORGANISMS, RELATIONS OF, TO 
DISEASE (1881), 387. 
Micro-organisms: cause shrinkage of blood-clot, 
196. 
relations of, to diseased processes in wounds, 399. 
neither inflammation nor suppuration always due 
to, 400. 
importance of, in regard to inflammation and 
suppuration exaggerated, 400. 
not present in healthy tissues, 408. 
do not survive in healthy body unless introduced 
in certain amount, 408. 
Microzymes: exposure to air and evolution of 
(Burdon Sanderson), 277. 
Milk: prevention of fermentative changes in, 310. 
production of viscous fermentation in, by 
bacteria, 321. 
lactic acid fermentation not produced by 
exposure of milk to atmosphere, 324. 
different actions of organisms on, 324. 
leptothrix filaments in, 325. 
coagulation of, 323. See also Coagulation. 
souring of, in summer weather, 324. 
dark pigment formed in, by growth of organism, 


329. 


423 


Milk (continued) : 

black deposit not caused by distinct ‘ pigment 
bacterium ’, 332. 

putrefaction of, 341. 

no inherent tendency to souring in, 342. 

no lactic acid fermentations in, when boiled 
and protected, 342. 

boiling of, does not prevent souring, 342. 

fermentations of other kinds in, caused by 
inoculation with unboiled water, 343. : 

estimation of number of bacteria in, 348. 

experimental production of lactic acid fermenta- 
tion in, 349. 

purification by heat, 358; difficulty of purifying, 
358 (footnote), 359; method of overcoming 
the difficulty, 360. 

almost all kinds of bacteria thrive in, 360. 

development of Bacterium lactis in, 362. 

as it comes from healthy cow contains no 
material. causing fermentative changes nor 
organisms, 364. 

Milk abscess: case of, treated antiseptically, 407. 

Milk, artificial: for experiment with organisms, 
216, 

preparation of, 316. 

Milk, boiled: process of charging, for experiment, 
313- 

Milk, curdled : growth of mould on surface, 374. 

Milk, souring: organisms in (Pasteur), 342. 

caused by lactic acid ferment, 366. 
cause of odour in, 376. 
bacteria become smaller in, 374. 

Milk, unboiled : not spontaneously prone to lactic 

acid fermentation, 344. 
organisms in, 344. 
contains no organism or ferment, 347. 

Miller: on lactic acid fermentation, 341. 

Minute organism. See Organism. 

Morphia: followed by administration of chloro- 
form produces insensibility to pain, leaving 
patient conscious, 174. 

hypodermic injection of, as a preliminary to 
chloroform administration, 174. 

Morton, W. T. G.: experiments on himself and on 

animals to discover anaesthesia, 135. 

painless extraction of tooth under sulphuric ether, 
135; demonstration of its use in Massachusetts 
General Hospital, 135. 


| Mould, blue, in milk, 363 (footnote). 


Mould, green, in milk, 363 (footnote). 
Mouse: flow of lacteal fluid in mesentery of, 25. 
Movements of heart. See Heart. 
Mucor mucedo in milk, 363 (footnote). 
Mucor vacemosus: in milk, 363 (footnote). 
and alcoholic fermentation, 379 (footnot/e). 
Mucus, vesical: the special ferment of urine, 358. 
Miller: disposition to coagulate in liquor san- 
guinis of frog filtered from corpuscles, 133. 
MUSCULAR FIBRE: INVOLUNTARY, 
NUTE STRUCTURE OF (1856), 15. 
Muscular fibre, involuntary : K6lliker’s views on, 15. 
J. F. Mazonn on, 106. 
G. V. Ellis on, 16. 
structure of, 218. 
Muscular tissue: in web of frog’s foot, 18. 
in intestine of pig, measurement of, 22. 
longitudinal striae in, 23. 
in stomach of rabbit, 23. 
‘ dots’ in, 


MI- 


23. 


424 


Muscular tissue, plain: Ko6lliker’s discovery of 
cellular constitution of, 1. 
Wharton Jones on muscular fibre-cells, 1. 
J. F. Mazonn on, 16. 
G. V. Ellis on, 16. 
Muscular tissue of skin: observations on, 9. 
not present in hairless parts, I4. 


Nélaton: his method of inversion in collapse 
during chloroform administration, 172; case 
illustrating the utility of this method, 173. _ 

Nerve-cells: in amputated limb of frog, producing 
irregular contractions after division of brain 
from cord, 39, 40, 41. 

Nerve-fibres : structure of, 99. 

Nerve of nerve-fibres (in collaboration with 
W. Turner): supplementary observations by 
author, 102. 

Nerve, sciatic: Wharton Jones’s observation on 
dilatation of arteries after division of, 28. 

Pfliiger’s observations on effects of galvanization 
and division of, within spinal cord, 29. 

effects of ligature of, on arteries, 209. 

recovery of contractility of arteries after section 
of, 30. 

effect of section of, in thigh of frog (Wharton 
Jones), 47. 

author’s observations on, 47. 

medullary sheath of, 100. 

axial cylinder of, 101. 

Nerve, sympathetic: Augustus Waller on effect on 
vessels and pupils of galvanization . above 
point of cutting or tying, 27. 

action on heart of branches connecting cord 
with cardiac ganglion, 93, 94, 95, 96. 

Nerves: of iris, 8. 

Nerves, mesenteric : 
testine, 9I. 

Nerves: paralysed by irritants, 259. 

Nerves, vaso-motor: experiments showing action 
of, 30, 31, 45, 46. 

Nerves, visceral: account of inquiry into their 
functions with special reference to so-called 
‘inhibitory ’ system, 87. 

function of, 232. 

Nervous action, excessive: producing inactivity 
of gland cells and other tissues, 273. 

Nervous activity: depression of, by chill, 405. 

Nervous apparatus : and post-mortem peristalsis, 90. 

Nervous centres for arteries: and dilatation of 
blood-vessels, 97. 

Nervous exhaustion: not cause of inhibitory 
influence of vagus, 97. 

Nervous shock, caused by cold, 405. 

Nervous sympathy: law of, 402. 

Nervous system: parts of, regulating contractions 
of arteries, 27. 

control of pigment cells by, 45. 

inflammation caused through, 400. 

its action in production of chronic housemaid’s 
knee, 406. 

Nitrite of amyl: as a cardiac stimulant in collapse 
under chloroform, 174. 

Nitrous oxide gas: as an anaesthetic (H. Davy), 
1357. (HH. Wells),°135. 

effects of, 154. 

mode of administration, 154. 

its uses in dentistry (Evans), 154. 
administration of, followed by ether, 174. 


inhibitory action of, in in- 


INDEX TO VOLUME I 


NoTES OF THE EXAMINATION OF AN EXoOSTOSIS, 
removed by Mr. Syme on October 2, 1853, 
from the os humeri of a young lady aged about 
twenty years (1854), 201. 


OBSERVATIONS ON THE STRUCTURE OF 
NERVE FIBRES (in collaboration with 
William Turner 1859), 99. 

Oedema, inflammatory: from bites or stings, 271. 

Oesophagus: bud of kail plant impacted in, 
causing uneasiness in epigastrium, 403. 

Ogston : micrococci in acute abscesses, 406. 

none in chronic abscesses, 407. 
Oidium: growth of, in unboiled and uncon- 
taminated urine, 294. 
in Pasteur’s solution, 295. 
Oidium lactis, 341. 
in milk, 363 (footnote). 
growth on curdled milk, 374. 

Oidium toruloides, a putrefactive ferment in urine, 

304. 
in Pasteur’s solution, 304. 
in albuminous liquid, 305. 

Organism : variation of, under influence of different 

media, 306. 

in putrefying blood, 338. 

Organism, spirilliform: growth of, in urine, 326. 
Organisms: fermentative agency of, 276. 

fissiparous generation in, 281. 

not present in urine drawn off after antiseptic 
treatment of skin around meatus, 278, 284. 

modification of, in urine and Pasteur’s solution, 
328. 

modification of function of, in different media, 331. 

assume specific properties in putrefying dis- 
charges, 333- 

in unboiled milk, 344. 

the cause of all true fermentations in organic 
liquids, 353. 

do not occur in liquids contained in pure covered 
glasses, 354. 

growth of, in milk, 363. 

different fermentative changes produced by, 363. 

development of rare kinds of, in milk in absence 
of ferments, 364. 

Organisms, minute: destroyed by strong watery 

solution of carbolic acid, 311. 

in Pasteur’s solution, identical with large ones in 
urine, 328. 

relation of, to inflammation, 399. 

Organisms, ultra-microscopic fermentative : 
sible existence of, 382. 

Ormsby: ‘close’ method of administering ether, 156. 

Os humeri. See Humerus. 

Oxygen: has no influence on coagulability of 
blood, 132. 

not cause of putrefaction, 283. 
and lactic acid fermentation, 382. 
and growth of organism in fowl cholera, 397. 


pos- 


Paget, James: statement as to use of chloric ether 
in St. Bartholomew’s Hospital in summer of 
1847, 136 (footnote). 

effects of irritants on circulation in bat’s wing, 
2 TT, 

reference to structure of blood-vessels, 218 (foo- 
note). 

degenerations of tissue resulting from inflamma- 
tion, 270. 


INDEX: TO VOLUME I 


Palatine stertorous breathing, 144. 

Pallor in web of frog’s foot caused by construction 
of arteries, 223. 

Palmar arch: treatment of wound of, 186. 

Palmer: reference to Astley Cooper’s experiments 
as to effects of injury of vessels on coagulation 
of blood, 77 (footnote). 

Parsons (of New York): death from congestion of 
lungs caused by ether inhalation, 156. 

BAR: le PAN SIO OGY, 1. 

PART . Il; PATHOLOGY 
LOGY.;201- 

Pasteur: his germ theory, 276. 

lactic acid fermentation produced 
organisms, 324. 

organisms in souring milk, 342. 

development of yeast plant in saccharine solu- 
tion, 350. 

his researches on fermentation, 353. 

his explanation of alcoholic fermentation in 
sugar, 377. 

action of bacteria in butyric fermentation, 379. 

fermentative action of Penicillium glaucum, 379 
(footnote). 

fermentative action of Aspergillus glaucus, 379 
(footnote). 

alcoholic fermentation checked by atmospheric 
exposure, 381. 

germs of bacteria, 384 (footnote). 

researches on fowl cholera, 390. 

method of attenuation of virus of fowl cholera, 
390. 

Pasteur’s solution: for growth of organisms, 2706. 

author’s modifications of, 286 (footnote), 315, 
372- 

bacteria in, 289. 

growth of oidium, 294. 

modification of, for experiments with organisms 
in milk, 315. 

dark pigment produced by bacteria in, 330. 

fermentation caused by yeast plant in, 336. 

Bacterium lactis does not live in, 342; incapable 
of growing in, 372. 

modification of; 372 (footnote). 

‘Pectous’ condition of ‘colloidal’ matter (Gra- 
ham), 129. 

Pelvic viscera: relief given in affections of, by 
raising lower limbs, 188. 

Penicillium glaucum, 275. 

carried into covered glasses by acari, 354 (Godlee, 
footnote). 

in milk, 363 (footnote). 

growth of, on curdled milk, 374. 

and alcoholic fermentation, 379 (footnote). 

mouldy smell produced by growth of, in paste 
or preserve, 380. 

Peristalsis: increase of, after death caused by 
arrest of circulation (Spiegelberg), 92. 

regulated by operation of intrinsic ganglia, 97. 

Peristaltic action of intestine (in rabbit): increased 

by spinal galvanism, 89. 
continuing after death, 89. 
See also Intestine. 

Pfliger: effect on arteries of galvanization and 
division of anterior roots of sciatic nerve 
within spinal cord, 20. 

his observation that galvanization of splanchnic 
nerves produces quiescence of small intestines, 
87. 


AND BACTERIO- 


in milk 


425 


Pfliiger (continued) : 

his theory of inhibitory system of nerves, 87. 

author’s verification of his statement as to local 
contraction caused by local irritation of 
intestine relaxed by inhibitory influence of 
galvanism applied to spine, 89. 

his statement that division of vagus in mam- 
mals causes increased action of heart, 93; 
this not confirmed by author’s experiments, 


93- 
Phlebitis : coagulation of blood in, 73. 
experiments on subject, 73, 74. 
Phosphorus: lowering of system in rabbits by, 
enables micrococci to enter, 408. : 
involuntary muscular fibres in intestine of, 


Pig: 


19. 
Pigment cells: control of, by nervous system, 
45- 
effects of poisons on, 66. 
diffusion of, caused by croton oil, cantharides, 
and mustard, 253. 
concentration of, invariable result of 
action, 254. 
functional activity of nerves of, impaired by 
irritants, 250. 
in web of frog’s foot, effect of irritants on, 
266. 
great susceptibility of, to irritation, 268. 
Pigment cells in frog’s skin, post-mortem con- 
centration of, 63. 
secondary diffusion at variable time after death, 
63. 
suggested existence of ganglionic 
co-ordinating actions of, 64. 

See also Chromatophorous cells. 
Pigment, dark: formed in milk by organism, 329. 
Pigment: in frog’s skin, comparison of changes 

in, after amputation, with those in arteries, 64. 

diffusion of, in web of frog’s foot caused by 
croton oil, cantharides, and mustard, indepen- 
dent of inflammatory process, 253. 

‘Pigment bacterium’ (Cohn’s), 329. 
causing black deposit in milk, not a distinct 

Species: 332; 

Pigmentary system: cutaneous, of frog, 48. 
author’s own observations on, 40. 
chameleon-like changes of hue in, 49. 
various arrangements of colouring matter, 50; 

light thrown thereby on nature of inflamma- 
tion, 65. 

effects of galvanism on, 247. 

effects of irritants on, 240. 

See also Chromatophorous. 

Pigmentary tissue: effects of irritants on, 249. 
effects of mechanical violence on, 251. 

Piles: relief given by raising lower limbs in, 188. 

Pneumogastric nerve. See Vagus. 

Poisons: effects of, on pigmentary system, 66. 

Position of a part: effect of, on the circulation 

through it, 176, 187, 188. 
Position: syncope in relation to, 172. 
effects of, on circulation, 172. 
effects of, on local circulation, 177. 
Post-mortem congestions: simulating inflamma- 
tion, 84. 

Psoas abscess. See Abscess. 

Pulse: mistake of over-estimating its importance 
in chloroform administration, 146. 

Pupil: sphincter and dilator of, 5. 


nerve 


apparatus 


426 


Pupil (continued) : 
contraction of, in cat or rabbit, from exposure of 
iris to light after death, 8. 
Purification of liquid from organisms by heat, 358. 
Pustule, malignant: Bacillus anthracis the virus 
of, 384. 
Putrefaction: germ theory of, 275. 
bacteria causes of, 277. 
not caused by oxygen, 283. : 
of blood, and bacteria, 338. 
of fermentation, 380. 
toxic infection with products of, and bacteria, 
Koch’s researches on, 388. 
distinct from pyaemia, 389. 
Putrefaction of milk, 341. 
Putrefactive fermentation: of blood, 337. 
not caused by oxygen of air, 337. 
Pyaemia: risk of, not increased by chloroform, 
" 148 (footnote). 
distinct from septicaemia and toxic effects of 
septic products, 389. 


Rabbit: contraction of pupil in, from exposure of 
iris to light after death, 8. 
muscular fibres in stomach of, 23 
experiments on movements of intestine in, 88. 
Rana temporaria, cutaneous pigmentary system of, 


49. 

Rayer: described bacterium of splenic fever, 387 
(footnote). 

Reaction of tissues after irritation, 268. 

Redness, intense : 
early stages of inflammation, 270. 

RELATIONS OF MINUTE ORGANISMS TO 
INFLAMMATION. ADDRESS ON (1881), 
399. 

Resolution, phenomena of, 258. 

Respiration under chloroform, 143, 144. 

restoration of, by pulling forward the tongue 

with artery forceps, 144. 


necessity of attention to, in chloroform adminis- | 


tration, 146. 

obstruction of, the chief danger in chloroform 
administration, 147. 

treatment of obstruction of, 148. 

experiments as to amount of air inspired per 
minute, 169. 

effect of, on arterial pressure, 187. 

See also Breathing. 

Respiration, artificial: in paralysis of respiratory 
nervous centres in chloroform administration, 
148. 

Sylvester’s method, 

Rest : 


L7 3 
has no influence on coagulation of blood, 
cz 
Retching: closure of larynx in, 146 (footnote). 
Richardson, Benjamin Ward : ‘his ammonia theory 
of coagulation of the blood, 70, 71, 72, 73, 82, 
105, 106, 1O9;, 001, T1G,9132.24 1 
reference to Scudamore’s researches on effects of 
injury to vessels and coagulation of blood, 77 
(footnote). 
his description of bubble of air within vessel before 
coagulation, 83; this, in author’s view, not 
connected with coagulation, but due to sub- 
sidence of red corpuscles, 83. 
his explanation of non- coagulability of blood 
shed from vessels below 40° Fahr., 106; and 
of rapid coagulation at high temperatures, 106. 


a post-mortem appearance in 


INDEX TO VOLUME I 


Richardson, Benjamin Ward (continued): 
effect of vacuum in promoting coagulation of 
blood, 115. 
ether spray as local anaesthetic, 155. 
hand bellows in chloroform inhalation, 166. 
Rigor: on passage of urine through urethra 
after lithotomy, 4o1. 
Roberts, W. (Manchester): sputtering of milk when 
heated for experiment, 312. 
Rouleaux: cause of arrangement of red cor- 
puscles in blood, 212. 


Sanderson, J. Burdon: and author’s method of 

recording blood pressure, 181. 

his experiments on bacteria, 276, 277; their rela- 
tion to antiseptic treatment, 277. 

fermentative agency in water consists of insoluble 
particles, 365. 

vaccination against anthrax, 392. 

‘Sarcous elements’ in muscle (G. V. Ellis), 17. 

Scalp: muscles of, 10. 

Schiff : on dilatation of small vessels in bat’s wing 
after destruction of cord in lower cervical and 
upper dorsal regions, 28. 

his observation that healthy action of heart is 
increased by gentle stimulation of vagus, 97. 

Schmidt, Alexander: new view on coagulation of 

blood, 189, 194; confirmed by author, 190. 
fibrinoplastic substance, 199. 

Schmidt (of Dorpat): observations on coagula- 
bility of dropsical effusions on addition of 
blood corpuscles, 130. 

extraction of soluble material from red corpus- 
cles, 130. 

author’s verification of his statement that a given 
amount of corpuscles causes coagulation of 
only limited quantity of hydrocele fluid, 131 
(footnote). 

composition of fibrin, 131. 

Schuler, Fr.: experiments on aggregation of red 
blood corpuscles caused by application of 
salt solution, 227 (footnote). 

stasis induced by application of irritants in 
amputated limb, 234. 

Schizomycetous bacteria, 326. 

Schwann: white substance of, in cord and nerves, 
100; description of, by Stilling, 102. 

Sciatic nerve. See Nerve. 

Scudamore, Charles: investigations on injury of 
vessels and coagulation of blood, 77. 

his opinion that coagulation of blood is promoted 
by escape of carbonic acid gas, I10, III. 
effect of vacuum in promoting coagulation, 115. 
“Separation tube,’ description of, 371. 
Septicaemia: Koch’s researches on, 388. 
caused by bacteria, 388. 
distinct from pyaemia, 389. 
different from chemically toxic effect of septic 
products, 389. 

Serous membranes: like lining membranes of 
vessels in relation to blood, 132. 

Serum, blood: does not coagulate per se under 
influence of solid matter, 129. 

indistinguishable from dropsical effusions or 
hydrocele fluid, 130. 

Sharpey, W.: letter to, entitled ‘ Preliminary 
Account of an Inquiry into the Functions of 
Visceral Nerves, with special | reference to the 
so-called ‘ Inhibitory System ’, 87. 


INDEX TO 


Sharpey, W. (continued) : 
action of heart the cause of circulation, 221 
(footnote). 
calls author’s attention to work by Germans on 
spontaneous changes of colour in frog, 248. 
effects of irritants on cilia, 260. 
Shock, nervous: caused by cold, 405. 


Shoulder joint: pain in, cured by application of | 


actual cautery, 404. 
Simpson, James Young: experiments with narcotic 
vapours, 136. 
first to use chloroform as anaesthetic in autumn 
of 1847, 136. 


large experience of use of chloroform without | 


accident, 137. 
‘ Sizy ’ layer in horse’s blood, 107. 
SKIN: OBSERVATIONS ON 
DISSUE OF (1853), 0. 
Skin, frog’s: pigmentary system of, 40. 
Skin of limbs: 
spinal nerves, 30. 

Skinner (of Liverpool): drop bottle and flannel 
bag for administration of chloroform, 167. 
Sneezing: prevented by violent rubbing of tip of 

nose, 402. 
Snow, John: death from fright when profession 
was made of administering chloroform, 139. 
experiments on effect of varying degrees of 
dilution of chloroform with air on heart, 
140. 

his inhaler for regulating amount of chloroform 
vapour in inspired air, 140. 

his attribution of deaths under chloroform to 
paralysis of heart, 140. 

statistics of deaths under chloroform during ten 
years, 142. 

chloroform administration in sitting position, 
147 (footnote). 

difference of effects of chloroform according to 
dosage, 158. 

experiments on dosage of anaesthetics, 162. 

two ways in which chloroform may kill, 163. 

percentage of chloroform by volume _ recom- 
mended for anaesthesia, 170. 


MUSCULAR 


Solids: influence of, on coagulation of blood, 127, | 


128, 1O1. 
Sore throat. See Throat. 
Spallanzani: the heart and the circulation in 


tadpoles, 221 (footnote). 
Spiegelberg, O.: demonstration that movement of 
intestines is increased by mechanical irritation 
of cord, 92. 
attributes increased peristalsis of intestine after 
death to arrest of circulation in part, 92. 
uterine contractions promoted by mechanical 
irritation of cord, 96; andarrested by powerful 
galvanization through spine, 96. 
Spinal cord: effect of division of all nerves from 
one side of arteries of lower limb, 30. 
method of demonstrating constriction of arteries 
in web of frog’s foot on irritation of, 32. 
variations of calibre in arteries (in frog) caused 
by removal of spinal cord at different levels, 


33, 35- 
hypothesis of spot about middle of, specially 
regulating contraction of vessels, 42; experi- 
mental evidence against this, 42, 43. 
mechanical irritation of, causes increase of move- 
ment of intestine, 92. 


LISTER I 


smoothness of, after section of | 


VOLUME I 427 


Spinal cord (continued) : 
medullary sheath of, roo. 
impairment of regulating function on calibre of 
vessels by chloroform, 224 (footnote). 

Spinal cord—divided—constriction of arteries on 
irritation of posterior segment of, 37. 

Spinal cord—undivided—contraction of arteries 
from irritation of anterior part of, 37. 

Spinal cord: Brown-Séquard’s observations on 
increase of temperature in paralysed parts 
after transverse section of, 28. 

Schiff’s observation on dilatation of small vessels 
in bat’s wing after destruction of lower cervical 
and upper dorsal regions of, 28. 

Waller and Budge on regulation of dilatation of 
pupil and vessels of face by, 27. 

Spinal system: influence of, on heart’s action, 
92, 93. 

influence of, on hollow viscera, 97. 

Splenic fever, bacterium of, described by Rayer 
and Davaine, 387 (footnote). ; 

caused by Bacillus anthracis, 388. 

vaccination against, 392. 

produced by injections of modified hay bacillus, 
390. 

SPONTANEOUS GANGRENE FROM ARTERI- 
TIS AND THE CAUSES OF COAGULATION 
OF THE BLOOD IN DISEASES OF THE 
BLOOD-VESSELS (1858), 69. 

Spontaneous gangrene: of lower limb from in- 
flammation of arteries, case of, 60. 

pathological appearances in, 70. 

Spontaneous generation: suspicious 
alleged facts, 284. 

evidence against, 310 

Stasis of blood in inflammation, 211. 

Sterilization by heat: method of, 354. 

Stertor, spurious: caused by approximation of 
vocal cords, 145 (footnote). 

Stertorous breathing. See Breathing. 

Stilling: description of medullary sheath, 102. 

his view as to constituents of nerve fibre, 102. 

this not confirmed by author, 102, 103. 

Stitches, tight: inflammation of skin produced 
by, 401. 

causing oedema and death of tissue, 402. 


nature of 


| Striae, longitudinal, in involuntary muscular fibre, 


Be 
He 
Stricture, urethral: shivering after passage of a 
bougie in, 4o1. 
Strumous disease, of joints: treatment of, 400. 
Strumous diseases: exaggerated tendency 
regard them as of infective nature, 400. 
complete extirpation of degenerated tissues not 
essential for cure of, 410. 
Strumous inflammation: treatment of, 409. 
Sugar: action of Torula cerevisiae on, 377. 
alcoholic fermentation of, 378. 
Sulphuric ether. See Ether. 
Suppuration: not always due to micro-organisms, 
400. 
micrococci not sole causes of, 407. 
Swallow: inability to, causing not hunger, but 
discomfort in epigastrium, 402. 
Sylvester: his method of artificial respiration, 173. 
Syme: chloroform given five thousand times 
without a death, 137. 
case of insusceptibility to chloroform, 143 (/oo- 
note). 


to 


Ff 


428 


Syme (continued): 
his teaching that attention should be devoted 
exclusively to breathing in chloroform ad- 
ministration, 147. 
never had a death under chloroform, 149. 
exostosis of humerus removed by, 201. 
case of carbuncle, 206. 
treatment of carbuncle, 207. . 
use of cautery in joint disease, 404. 
Sympathetic nerve: in neck, effects of division of, 
on blood-vessels of ear and side of face, 27. 
effects of galvanism after cutting or tying, 27. 
presides over contraction of vessels of face, 27. 
Sympathetic nerve: Claude Bernard on effect of 
division on blood-vessels of ear and face, 27. 
Sympathetic nerve: Brown-Séquard on elevation 
of local temperature after section of, 27. See 
also Nerve. 
Sympathy, nervous: 
related parts, 401. 
law of, 402. 
Syncope: slight risk of, in chloroform administra- 
tion, 147. 
and position, 172. 
Synovial bursa of patella. 


causing inflammation in 


See Bursa patellae. 


Tait, Lawson: death from failure of heart during 
administration of ether, 158. 

Temperature, and blood coagulation, 106, 108. 

experiments on this point on sheep, 106; on 
horse, 107. 

effect of, 116. ; 

relation of, to ammonia theory (Richardson), 116. 

experiments on, 116, I17, 118. 

Testicles: relief of pain in, given by sitting down 
and putting up feet, 188. 

Thackrah: action of living vessels due to nervous 
influence on coagulation of blood, 111. 

Thomson, Professor: cause of crystallization of 
supersaturated solution of sulphate of soda, 
196. 

Throat, sore : 

; 403. 

Tissues: persistent vitality of, illustrated by liga- 
ture of brachial artery, 85. 

effects of irritants on, 246. 

relation of, to coagulation of blood, 242. 

functional activity of, impaired by galvanism, 
248. 

inherent power of recovery from irritation, 257. 

temporarily deprived of power by irritants, 
nature of change in, 267. 

difference in facility with which they are affected 
by irritants, 268. 

Tissues, healthy: continuance of vitality in, after 
withdrawal from centres of circulation and 
innervation, 86. 

Tissues, living: properties of, with reference to 
blood, 132. 

Tongue, ‘ falling back’ of, does not cause obstruc- 

tion of breathing, 144. 

longue, traction of: in chloroform asphyxia, 144, 
150. 

makes stertorous breathing impossible, 144. 

causes retirement of mucous membrane in con- 

_ tact with epiglottis, 145. 

in obstructed breathing acts not mechanically 
but through nervous system, 146. 

case illustrating its value, 150. 


pain of, eased by mustard poultices, 


INDEX TO VOLUME I 


Torula cerevisiae : 275, 339, 377- 
much larger than Bactertum lactis, 382. 
See also Yeast plant. 
Torula ovalis: growth of, in urine, 285, 287. 
developed from filamentous fungus, 290. 
Torulae: natural history of, 275. 
forms scum on surface of urine, 282. 
in atmospheric dust, 283. 
Toussaint: micro-organism causing fowl cholera, 
390. 
researches on Bacillus anthracis, 392. 
inoculation of calf against splenic fever, 392. 
experiments on production of immunity against 
anthrax, 393. 
vaccination against anthrax, 398. 
Toxicological inquiry: service of pigmentary 
system in, 606. 
Transfusion of blood: does not cause coagulation, 
198. 
Tree frog. See Frog. 
Turner, William, and author: 
structure of nerve fibres, 99. 
Turnip infusion: for experiments with organisms, 
316; preparation of, 316. 
growth of bacteria in, 322. 


observations on 


‘Ulceration of cartilage’: between upper cervical 
vertebrae cured by application of actual 
cautery, 404. 

Uraemic poisoning : 
flammation of kidneys 
system, 401. 

Urari: effect of, on pigment cells in frog’s skin, 66. 

Urethra: irritation of, leading to disturbance of 
kidney, 401. 

rigor on passage of urine through, after litho- 
tomy, 401. 

Urethra, healthy: bacteria cannot grow in mucus 
of, 275% 

Urethral mucous membrane: when healthy, free 
from septic organisms, 309. 

Urine: expulsion of, in lower animals from fear, 


death from, caused by in- 
through nervous 


97- 
growth of organisms in, 277. 
unboiled, more favourable nidus than boiled for 
growth of organisms, 281; method of obtain- 
ing it uncontaminated with organisms, 357. 
protected from air, no growth of organisms in, 
283. 
growth of oidium in, 294. 
used for experiments with organisms, 317. 
different modes of growth of bacteria in, 326. 
spirilliform organism in, 326. 
modifications of organisms in, 328; and in 
Pasteur’s solution, 328. 
vesical mucus the special ferment of, 358. 
Bacterium lactis become smaller in, 384 (footnote). 
suppression of, caused by urethral irritation, 401. 
Urine: Gvanuligera causes of putrefaction in, 282. 
Uterus: contractions of, promoted by mechanical 
irritation of cord, 96. 
arrested by powerful galvanization of spine 
(Spiegelberg), 96. 
Uterus, relaxed: contraction of, produced by 
application of cold towel to hypogastrium 
and vulva, 401. 


‘ Vaccination’ against fowl cholera, 392. 
against anthrax, 392, 393. 


INDEX TO VOLUME I 


Vacuum: efiect of, in promoting coagulation of 
blood (Scudamore), 115; (Richardson), 115 ; 
experiments on, 115; no proof of ammonia 
theory, 110. 

Vagus: division of, in heart, said to cause increased 
action of heart in mammals (Pfluger), 93; 
this not confirmed by author’s observations, 
DOr ok : ; ; 

gentle stimulation of, increases heart’s action 
(Schiff), 97. 

Valentin: his observations that mechanical or 
chemical irritation of vagus in neck soon 
after death causes contraction of ventricles 
of heart, 95. 

Vaso-motor apparatus: in limbs stimulated by 
artificial bloodlessness, 183. 

and effect of position on circulation, 188. 

Vaso-motor nerves. See Nerves. 

Vein: effect of lesion of, on coagulation of blood, 
Ts 

Vein, ee uncertainty of duration of vital 
properties of, 122. 

Veins, contractility of: slight, in frog, 222. 
examples of, in higher animals, 222 (footnote). 
Veins, varicose: do not impede return of blood 

to heart, 187. 

Vertebrae: inflammation of upper cervical, caused 
by actual cautery, 404. 

Vesical mucus: the special ferment of urine, 
358. 

Vi esication : process of, described by John Hunter, 
269. 

resulting from continued pressure, 271. 
Vessels : influence of, on contained blood, 76, 79. 
coagulation of blood induced by introduction of 
solid matter into, 106. 

Vibrissae : absence of unstriped muscle in, 14. 

Virchow : his observation that on introduction of 
mercury into heart blood coagulates only 
around globules of metal, 108. 

Virulence of organism modified by special method 
of culture, 392. 

Virus: no special, in hospital gangrene, 333. 

Virus of fowl cholera: Pasteur’s method of 
‘attenuation ’ of, 396. 

Viscera, hollow: influence of spinal system on, 97. 

Visceral nerves. See Nerves. 

Viscous fermentation, in milk: 
bacteria, 321. 

‘Vital properties: ’ explanation of term, IIo. 

lost sooner by heart and large vessels than by 
smaller, 124. 

Vital theory of blood coagulation, 121 ; 
ment demonstrating, 121. 

Vitality of blood-vessels: its relation to coagula- 
tion, 193. 

Vitality of coats of blood-vessels and coagulability 
of blood, 77. 

Vitality of tissues. See Tissues. 

Volkmann, A. W.: experiments on effects of 
injections of water into arteries removed from 
body, 179 (footnote). 

Vomiting: closure of larynx in, 146 (footnote). 


produced by 


experi- 


429 


Vomiting under anaesthesia : comparison between 
chloroform and ether inthis respect, 154, 166 ; 
risks of, 166. 


Waldie: his suggestion of chloroform 
anaesthetic to Simpson, 136. 

Waller, Augustus: effects of galvanizing sympa- 
thetic nerve in neck above point of cutting or 
tying, 27. 

Waller and Budge: regulation of blood-vessels of 
face by spinal cord, 27. 

Warren, J. Mason: advantages of sulphuric ether 
as an anaesthetic, 153. 

Water: scarcity of lactic ferment in, 364. 

fermentative agency in, consists of insoluble 
particles (Burdon Sanderson), 365. 
bacteria in, 383. 

Weber, Edward: reference to his experiment of 
stopping heart’s action by stimulating vagus, 
87 

induction of inhibitory action on heart by 
galvanization of posterior part of brain, 93. 

Weber, H. (of Giessen): stasis caused by application 
of irritants to frog’s foot after ligature of thigh 
234 (footnote). 

Weber (of Leipzig): effects of heat or cold on 
cilia, 264 (footnote). 

Wells, Horace: his use of nitrous oxide gas as an 
anaesthetic, 135. 

‘White swelling’ of knee: treated by antiseptic 
incision and gouging, 410. 

Williams, C. J. B.: adhesion of white corpuscles 
to walls of vessels in irritated part, 237. 

Wittich, von: observations on the variations in 
colour of the skin of the frog, 48. 

Wohler: action of emulsion on amygdalen, 330. 

Woolsorter’s disease : caused by Bacillus anthracis, 
388. 

Wounds: putrefactive fermentation in, 3 

relations of micro-organisms to diseas 
cesses in, 399. 
healing of, without suppuration, 400. 

Wounds, contused : plugging of divided vessels by 
coagulation in, 78. 

Wrist: excision of, 176, 409. 

strumous disease of, treated by free antiseptic 
incision, 409. 


as an 


2 
ed pro- 


Yeast plant: 275. 

alcoholic fermentation of grape sugar due to, 330. 

Pasteur’s view of origin of, in juice of grape, 336. 

fermentation caused in Pasteur’s solution by, 
330. 

development of, in saccharine solution (Pasteur), 
350. 

and alcoholic fermentation, 377. 

its action on sugar, 377. 

catalytic action of, in sugar (Liebig in /ootnoie), 
380; (Pasteur in footnote), 381. 


Zone maniable in anaesthesia (Paul Bert), 170. 
Zones of anaesthesia (Paul Bert), 161, 170; their 

existence not confirmed by author, 164. 
Zymotic diseases, 335. 


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