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ON THE

ANIMAL ALKALOIDS

THE PTOMAINES, LEUCOMAINES, AND EXTKACTIVES
IN TflEIE PATHOLOGICAL RELATip^.-^^.^

BY

SIR WILLIAM AITKEN, Knt., M.D., LL^IT^E^.

PROFESSOR OF PATHOLOGY IN THE ARMY MEDICAL SCHOOL.

SECOND EDITION

LONDON

H. K. LEWIS, 136 GOWEK STREET, W.C.
1889

PRINTED BY
H. K, LEWIS, 136 COWER STREbT,
LONDON, W.C.

ROYAL CO. : C" rnYSIOIANS

C-AS^i 5«+7 9^'

SOURCE I
OATt

PEEFACE TO THE SECOND EDITION.

The lirst edition of this little volume having been
disposed of by the publishers in a comparatively short
time, I gladly avail myself of the opportunity which the
call for a second edition presents, to express my
acknowledgments for the reception which the first
has met with.

This new edition has not only undergone a careful
revision, so as to remove some inaccuracies and other
blemishes, but it has been my aim in it to bring the
subject up to the present state of knowledge regarding
the Animal Alkaloids, and generally to make the work
more complete without altering its original character —
namely, that of giving a concise account in small
compass of recent discoveries regarding the Animal
Alkaloids, and their relation to diseases.

The discovery of these substances is so comparatively
recent that the important problems of their relations to
diseases as causative factors have nob yet been suffi-
ciently appreciated by the profession. While, therefore
the subject is of much interest, it is comparatively new,

vi

Preface to Second Edition.

and it deals with phenomena and researches of a very
practical character.

But while the direction of modern thought tends to
assign an important place to the part played hy Animal
Alkaloids in the production of diseases, any conclu-
sions drawn in the present state of our knowledge must
be considered merely as suggestions. Many more
facts must come to light before the role played by the
Animal Alkaloids in living pathological processes can be
adequately or even reasonably discussed. The re-
searches of the last 17 years (of which a resume is
given in this volume) can only be regarded as a basis
for future work, and be suggestive as to its scope and
method.

Nevertheless from a practical point of view some im-
portant considerations at once arise out of this study of
the Animal Alkaloids in their relation to disease, especi-
ally as regards treatment, inasmuch as a great deal
may be done, alike in the prevention and cure of
disease by attention to the personal Physiological
Pathology of the patient.

From this practical view of the subject the cardinal
idea embodied in this volume points : — (1) to the evolu-
tion of diseased states from retention in the body of its
own " excretions," and of the products of their decom-
position ; (2) to the consequences and direct issues
of inadequacies of function, as regards especially the
cutaneous, intestinal, hepatic, pulmonary, and renal
functions.

These considerations are of wide application, and of

Preface to Second Edition.

vif

extreme importance in medical practice, and in tliis
view of tlie subject I am pleased to find myself borne
out by the authority of the present distinguished Pre-
sident of the Royal College of Physicians of London —
Sir Andrew Clark,

We have now also arrived at that stage in our know-
ledge when we can appreciate the ideas of autogenetic-
and of bacterial infection, as so closely related, and so-
curiously interwoven in their actions and results, " that
the true place of Bacteriology in Scientific Medicine
cannot be finally determined until the chemistry of the-
functional processes of living protoplasm (including the
living blood and the hving bacteria) have been further
advanced, and until the relation of the Animal Alka-
loids and ' Extractives ' to the genesis of pathological
processes have been experimentally investigated anew."'

And even if the bacterial origin of all infective dis-
eases were to be fully estabUshed, the main teachings
of this little book would still hold good, namely : — the
gi-eat importance of soundness of tissue, and " adequacy
of function"— not only of the larger organs, but still
more so as regards the soundness of protoplasm and of
the vitality and functional activity of each individual-
component cell of the living body, seeing that it is in
the soundness and vitality of the blood and tissues, and
the presence in them of those normally characteristic
chemical substances which are the result of their healthful
life, that our safety lies, and in which the power exists
of checking the ingress and progress of all micro-organ-
isms (whether psithogenic or non-pathogenic) by the-

viii Preface to Second Edition.

direct adequacy of the vital reactions of those tissue
elements themselves. Undamaged tissues of standard
vitality (i.e., standard adequacy of function) perfectly
resist the entrance of invading organisms ; on the
other hand, damaged tissues with lowered vitality or
impaired adequacy of function favour the entrance of
pathogenic organisms whence the body may become
an easy prey to their influences.

WILLIAM AITI^EN.

Army Medical School, Netley.
October, 1889.

PREFACE TO THE FIRST EDITION.

The following pages owe their existence to the neces-
sity of finding a subject suitable for a lecture intro-
ductory to the course of instruction at the Army
Medical School at Netley, on the 1st of April, 1887.
They are now pubhshed by request ; and with the
permission of the Secretary of State for War.

Speaking generally, it may be stated that the investi-
gations which underhe the most important practical
work of the Military Medical Officer, alike on land
and sea, relate especially to the causation of diseases
with a view to their prevention ; and in carrying out
such investigations, the time appears to me to have
come when it is desirable to open up new lines of
thought and of practical departure in Pathology, which
may lead us to entertain broader, or at any rate less
narrow views, than those we have been accustomed to
entertain as to the origin of some diseases.

By the selection of a topic such as the following
pages concern, I hoped that I might awaken in youug,^
ardent, ingenuous and impressionable minds, a desh-e
to work out various philosoijhical i^roblems in Patho-
logy ; wliile the nature of the Military Services the
young medical officers were about to join would give

. X Preface to First Editiun.

tliem leisure not only to study and to work out, but
would give them also opportunities in many climates
and in many lands to add to our knowledge regarding
the causation of disease.

When I had the honour of discharging a similar
duty two years ago, I endeavoured to show how far
" The Doctrine of Evolution " was competent to ex-
plam the origin of some diseases and now I once
more try to open up to view another new and fresh
territory in Pathology only just beginning to be ex-
plored, which is calculated to render obvious certain
modes of origin of many forms of disease. I do so
in the hope that the glimpse I am able to give of
this fresh field, however hazy its vista may be ; yet
as Time (with increasing knowledge) clears away the
mists of our ignorance, lines of thought and inquiry
may suggest themselves in many fruitful du-ections
for investigation.

While much remains to be done in the du-ection
indicated in the following pages, yet so much has
been already done by experiment and research in the
past twelve or fifteen years, that such a concise sum-
mary as I have here attempted to give may show the
bearing of the results and their value, as illustrating
the Pathology and the origin of some diseases.

It is further desirable, if possible, to get rid of the
term " cause " altogether as apphcable to any par-
ticular disease. Our textbooks, as yet, have been
unable to specify and estabUsh any simjle thing as.

* " Glasgow Medical Jouinal"'

Preface to First Edition.

XI'

the final cause of any disease. There is no disease I
know of which acknowledges a single cause.

It ought rather to be our business to find out the
many and ever varying factors or conditions which,
as antecedents, combine to produce disease ; and while
we must acknowledge the influence of many physical
agents in aiding and abetting these factors, we must
mainly look to the physiological agencies within our
own bodies during life as competent to bring about
many forms of disease.

WILLIAM AITKEN.

Army Medical School, Netley.

CONTENTS.

PAGE

1. Chemical and physiological aspect of the subject: — Nomen-

clature and meaning of terms — Discovery of Animal Alka-
loids— Elaboration of alkaloids througL decomposition of
proteid substances (ptomaines) — Through normal cell-life
(leucomaines) — Elaboration of azotised crystallisable sub-
stances (extractives) — Their toxic properties — Similarity
of Animal and Vegetable Alkaloids — Poisonous nature of
Peptones — Leucomaines the necessary products of vital
physiological processes — Synthetical formation of some
organic bodies — Continuous formation of poisonous alka-
loids in the intestines, the urine, and the tissues generally —
Classification and chemical constitution of some of the
physiological alkaloids 1 — 16

2. Clinical, pathological, and pracUcaZ aspects of the subject ; —

Poisonous character of ptomaines and leucomaines — Patho-
logy and symptoms of poisoning by extractives and by
animal alkaloids — Poisoning by the accumulation of nor-
mally elaborated but toxic products — Origin in this way of
Bome constitutional diseases — Constant exposure to auto-
infection— Physiological pathology of fatigue and fatigue-
fever— Discovery of anthropotoxine by Du Bois-Raymond —
The typhus of armies and of camps— Alkaloids in bodies
dead of typhus fever— De novo origin of typhus— Circum-
stances under which typhus has arisen in epidemics — Typho-
toxin from cases of enteric fever — Elaborate arrangements
for removal of its waste products in the living body . 16—37

Contents.

Phenomena in relation to Animal Alkaloid poisoning — Botulism
— Ptomaines in the intestines — Ptomaines from milk,
cheese, and tined fish — Indigestion from ptomaines a
cause of nervous depression— Danger in aheyance of liver
function — Absorption of digestive juices— Albuminous sub-
stances, peptones and extractives in the urine — Eflfects of
bile-acids in the blood — Action of peptones on the blood
and its circulation — Poisonous alkaloids formed during food-
decomposition — Symptoms of poisoning from alkaloids of
putrefaction — Indigestion a cause of nervous depression —
Absorption, of poisonous matters generally in intestinal
canal — Preventive function of the liver — Products of nitro-
genous waste in the urine — Products of digestion may
become poisonous in themselves — Nature of peptones has
still to be investigated 37 — 47

Poisonous alkaloids formed from foods, and their relation to
biliousness and diarrhcea — Proteid substances yield poison-
ous "ptomaines" or " leucomaines " by digestive ferments
— Variations of these self-generated poisons — Influence of
electrical and atmospheric conditions — "Tainting" of meat
and milk — symptoms of poisoning by the putrefactive alka-
loids— Indications of musoariue-like poisoning — Indications
of atropine-like poisoning — Poisoning by fish — Mackerel
poisoning (note) — Atropine as a remedy in muscarine-Uke
poisoning — Formation of poisonous alkaloids in the intes-
tines— Bouchard on " self intoxication in disease " — Sir
Andrevf Clark on " Chlorotio Ancemia "—Alkaloids se-
parated by the kidneys and found in the urine — Production
of thrombosis in the puerperium— Amount of ptomaines
formed in disease greater than in health— Investigations of
of Dr. Dixon Mann and Dr. Luff— Diabetic coma— Aceton-

Contents.

XV

PAGE

Pathological series of phenomena following the ingestion of
Animal Alkaloids — Diseases are not "entities" — ^Humoral
Pathology — Legislation in this country tends to hinder
progress in pathology, and obstructs the advance of medical
Science — Bacillary Pathology — Parasitical Causation of
some diseases — Infectivity of diseases through micro-organ-
isms— Bacterial affections very widely diffused— Causal rela-
tion between micro-organisms and disease — MM. P. Bert,
Jaillard and Laplat's experiments, also those of Brauell,
Bouley, Bollinger and Oniraus — Products of a poisonous
nature result from growth of bacteria — Fallacies which beset
bacterial methods of investigation — Brieger, Dixon Mann and
Bocklisch's experiments and results — Modification of views
now entertained by the Author regarding micro-organisms
in relation to infective diseases — Dr. Koch's canons for deter-

i mining the causal relation of micro-organisms to disease —
Anthrax, relapsing fever, and Malta fever proved by those
canons to be due to the constant presence of definite micro-
organisms to which may be added tniherculosis, lupus, leprosy,
and perhaps glanders, erysipelas, gonorrlicea, and forma of
septiccemia, contagium vivum of erysipelas, variola, vaccinia,
diphtheria, and pneumonia — Enteric fever, measles, cow -pox,
sheep -pox, ague, cholera, are still subjects of controversy as
to bacilli found in them — Relation of microbes to generation
of poisons by them — Chemistry of putrefaction and zymotic
diseases— Peptonising ferments from bacilli— Relation to
meat poisoning — Cholera and choleraic diarrhoea — Various
theories regarding mode in which bacilli cause death — A pto-
maine from bacillus anthracis — Wooldridge's experiments —
A ptomaine in puerperal fever, in tetanus, in diphtheria, in
rabies — The microbe the maker of the poison- Protection
afforded by its inoculation — Animal Alkaloid poisons and
ferments or zymotic poisons — Fliigge's classification of
micro-organisms 59—98

XVI

Contents.

PAGE

Study of the urine in relation to "extractives" and Animal
Alkaloids— De Cbaumont's method of estimating urinary
constituents — Weight of the unknown extractives, the
a, y, z's, of pathology — Mr. Harrison on the fever following
catheterism — Summary of Bouchard's researches in "Toxic
urine" — Symptoms of urinary toxasmia — Varying amounts
of urinary poisons in sleeping and waking hours — Relation
of the toxic alkaloids to the disease causing death — Import-
ance of the subject from a medico-legal point of view — Key
to the identification of pathogenic ptomaines — Lethal
potency of animal alkaloids from bodies dying of infective
diseases — Their difference from toxic ptomaines obtained
from putrefying animal tissues — Experimental difficulties
of the subject — Influence of the science of chemistry on
pathology — Question as to the usefulness of scientific mis-
sions to find specific things — Failure of attempts to photo-
graph micro-organisms — Accurate drawings more useful —
Discoveries are slowly elaborated through many minds —
Difficulty of appreciating the value of discoveries and of
comprehending their significance when first made . . 93— 102

Appendix. —Method of obtaining animal alkaloids from urine of

enteric and scarlet fever 103 — 105

Index

105—112

ON THE ANIMAL ALKALOIDS.

The -word " alkaloid " is used in chemistry to denote a
class of substances having alkaline properties, that is
to say, having in some degree the qualities which alka-
lies (such as soda and ammonia) possess of being
soluble in water, and of combining with acids to form
salts. Their generic name (derived from the Arab
" qaU," signifying the ashes of the plant or the plant
itself from which soda was first obtained) denotes a
plant connection. Until recently, the vegetable was
believed to be the only source whence these sub-
stances were obtained; and they were regarded as
natural alkaloids, the organic basis existing already
formed in plants. But it has now been conclusively
shown that the living animal cells are capable of
elaborating alkaloids, so that henceforth it may be
convenient to classify alkaloids into two classes,
namely : — the vegetable and the animal alkaloids, and
to sub-divide the animal alkaloids (as Gautier has done)
into (1) those due to the action of bacteria (or ferments
which may be fluid or solid) on the albuminoid sub-
stance of the dead tissues (ptomaines), and (2) those
elaborated by the vital energy of the cells themselves
(leucomaines). Moreover, the recent researches and
expositions of MM. Gautier and Peter (two eminent
French physiological Chemists and Physicians), of Drs.

B

2

The Animal Alkaloids.

A. M. Brown and Lauder Brunton and others in this
country, have furnished numerous facts, which (apart
from their chemical and medico-legal value) have the
important merit of confirming our helief in "the
poisoning or intoxication of the animal economy with
its own products." In this direction they have added
to our previous knowledge ; and to pathological investi-
gation they have imparted a greater degree of method
and precision than heretofore. But it is to the writings
of Dr. A. M. Brown,- and those of Dr. T. Lauder
Brunton,! that I am mainly indebted for the facts and
arguments contained in the following short notice of the
animal alkaloids.

What then are the questions involved in the subject
matter of the researches of these eminent physicians ?

They may be considered under two aspects: — 1.

* " Contributions to the Study of tbe Cadaveric Alkaloids, the
Ptomaines and Leucomaines ; their Physiological and Pathological
Significance in Relation to Scientific Medicine," 1886. "MM.
Gautier and Peter on the Ptomaines, Leucomaines, and Microbes,
a New Departure in Pathology." " Contributions to the Study of
the Animal Alkaloids; Leucomaines, their Antecedents and Dis-
covery, their Classification and Chemical Definitions," 1887. "The
Animal Alkaloids, Ptomaiues, and Leucomaines ; their Common
Origin, a fresh page in Bio-Cheraics," 1886. (Published by John
Bale and Sons, 89 Great Titchfield Street, London). Also by same
author and publisher, 1887, a very exhaustive "Treatise on Cadaveric
Alkaloids and Ptomaines," in which he gives full details as to the
methods devised and practised for extracting the cadaveric alkaloids;
and as to the chemical properties of them, their physiological action,
and place in scientific medicine; concluding with a very complete
Bibliographical list of the works which deal with this very interesting
subject.

f " Disorders of Digestion," comprising various papers from " The
Practitioner," 1873 to 1885, collected aud published 1886. "Phar-
macology, Therapeutics, and Materia Medica." Third Edition.
London, Macmillan and Co., 1887 ; also Croonian Lectures, 1889.

Their Chemical arid Physiological Aspect.

3

Chemical and physiological or bio-chemical. 2. Clini-
cal or pathological.

1. As to the chemical and physiological aspect,
Gantier has shown that in dead animal tissues, pro-
cesses of j)utrefactive decomposition set in by which
certain alkaloids are elaborated from the proteid sub-
stances, which by the late Selmi, of Bologna, have been
called " ptomaines."* But Gautier has further shown
that in the animal tissues during normal life, and that
by virtue of their vitahty, certain other alkaloids are
elaborated which are analogous to the "ptomaines,"
and these he has named "leucomaines."f Still further
in addition to these facts, he has demonstrated that in
the living animal economy there are elaborated certain
azotised uncrystallisable substances, which are as yet
undetermined, which we call "extractives" or "ex-
tractive matters," and which are quite as unknown as
the X, y, zs of an algebraical formula (Dr. H. L. Veale).
The nature of these " extractives " has therefore stUl to
be found out ; but this much we know of them : that

* " Ptomaines from Jlrufia, a carcase, a dead body, and iim, de-
noting material ; or In, from Latin inus, lelonging to. A common
termination in chemical terms, but varying much in significance, as
hcemaUn, hcematine, stearin, stearine, innulin, etc. Ine or in has
been usually applied to the alkaloids produced from vegetable sub-
stances, and the compounds possessing the closest analogies to them,
e.g., quinine, atropine, amiline.

+ Aivxa/ia, anything whitened— albumen, or white of egg.

The nomenclature is not quite satisfactory. The selection of the
word "ptomaine" indicative merely of the conditions under which
animal alkaloids were first discovered, as a root whence to derive a
name for these bodies is too restrictive, since it is only appropriate
for alkaloids of post-mortem origin. A name is still wanted for
animal alkaloids formed by morbid processes during life— tho
ptomaines of disease formed during life.

b2

4

The Animal Alkaloids,

while we are assured that the "ptomaines " are toxic,
and that the " leiicomaines " are also toxic, these un-
Imown " extractives " are more toxic or i^oisonous to
the system than either.

Take for example the urine ; we know that by or
through it we eliminate chlorides, phosphates, urea,
glucose, albumen, and " extractives," in variable
amounts, and that these go to make up the total
solids of the urine, "We know further, the chemical
composition and the dangers of all of these, when
found in over abundance or when not ehmiuated,
except as regards the unknown and mysterious " ex-
tractives." We know further, that in proportion as
the cypher of albumen increases in the urine, those of
the urea and extractive matters diminish, and a series
of accidents supervene which we name " ursemic," as
the non-eliminated extractive matters (which are re-
tained) increase in the blood. It may also be noted, as
was pointed out to me by my friend the late Dr. F. de
Chaumont, that when the glucose is in excess, some
inhibitory influence seems to be exercised over the
eUmination of the extractives, so that they seem less in
quantity ; but whether their actual formation is pre-
vented, or merely their ehmination, is not known.

The alkaloids of animal origin were first discovered
by Ai'mand Gautier in 1872. He discovered them in
the ammoniacal products of putrefaction of albuminoid
material, a discovery which excited much interest ;
especially when sometime afterwards Selmi, of Bologna,
pubhshed his researches (from 1878 to 1882) confirm-
ing the observations of the Chemist of the College of
France in their medico-legal applications. These
researches and their results were worked out by those

Discovery of the Animal Alkaloids.

5

eminent toxicologists independently of each other.
Selmi's investigations were unfortunately too soon
brought to a close by his early death. In 1877 he
extracted two new alkaloids from pure albumen which
he had caused to undergo putrefaction free from atmos-
pheric contact.

But so long ago as 1820, Kerner pointed out the
resemblance between the symptoms of poisoning by
sausages and by atropine. He was thus the first to
raise the suspicion that alkaloids were formed through
the decomposition of albumen ; and by the experiments
on animals which he made, he appears to have come to
the conclusion that an alkaloid was present in poisonous
sausages ; although he afterwards came to regard fatty
acids as the really poisonous agent in them.

In 1856 Panum showed that the ■ inflammatory
change which occurs in the intestinal mucous mem-
brane of animals poisoned by putrid matter, is due to
a chemical poison which remained unaltered when its
aqueous solution was boiled for a long time ; and his
conclusion that the poison contained in putrid matter
was of a chemical nature, was confirmed by C. 0.
Weber, Hemmer, Schweninger, Stich and Thiersch.

Fourteen years ago Dr. W. B. Eichardson showed
that sero-sanguineous fluid from the peritoneal cavity
of a person suffering from pytemia could communicate
fatal disease from one animal to another in a dkect
series. To this poison he gave the name of " septine."
He also found that it could be made to combine with
acids so as to form salts, and that these retained the
poisonous qualities of the original substance.**

* " Lancet," April 3rd, 1875. " British MedicalJournal," May 27th,
1876, Aitken's "Science and Practice of Medicine," 7th edition,
vol. i., p. 376, 1880.

6

The Animal Alkaloids.

Bergmann and Schmiedeberg isolated a cryBtalline
poison from decomposing yeast, to which they gave the
name of " sepsin."

Bence Jones and Duprd found a substance re-
sembhng quinine in the liver.*

Zuelzer and Sonnenschein obtained both from ma-
cerated dead bodies and from putrid meat infusions,
small quantities of a crystallisable substance which
exhibited the reactions of an alkaloid, and had a
physiological action like atropine, dilating the pupU,
paralysing the muscular fibres of the intestine, and
increasing the rapidity of the pulse. t

Korsch and Fasbender obtained from dead bodies a
substance which had properties like digitaline, but
which was not crystalline,

PeUicani has found a poison in the supra-renal
capsule, and sometimes ptomaines may be obtained
from the flesh of healthy animals.J

An alkaloid has been separated by V. Anrep from
poisonous fish,§ so also Vaughan has obtained an
alkaloid from poisonous cheese, which he has named
" tyro-toxican."|| The development of this substance
in milk is a frequent cause of diarrhoea in infants. It
has also been found in ice-cream and oysters. IT

But while the question in Italy was confined to
researches in toxicology, in France first and afterwards
in Germany it took a position more important and
wider in its range.

* Zeitschr. f. Chem. u. Pharm., 18S6.
t Berlin Klin. Wochensclir., 1869.

I Dr. Lauder Brunton, loc. cit. p. 282.

§ "London Medical Kecord," 1885, p. 271.

II " Lancet," August, 1885, p. 60.

IT Victor 0. Vaughan, University of Michigan, 1886.

Similarity of Animal and Vegetable Alkaloids. 7

Gautier, Etard, Brieger, and others gave precision to
the data previously acquired ; and adding largely to
the varied and careful examination of cadaveric tissues,
" they forced the conclusion that during the putrefac-
tion of nitrogenous animal material there are formed
organic bases, fixed or volatile, i^resenting by their
chemical and physiological properties, the closest
similitude to the vegetable alkaloids."* They have
succeeded in isolating a number of these ptomaines in
,the crystalline form and have submitted them to ulti-
mate analysis.

It was at first supposed that these animal alkaloids
differed in their nature from the organic alkaloids
formed by vegetables, and various reactions had been
given to distinguish between them. More recent
researches, however, especially those of Brieger appear
to show that this distinction can be maintained no
longer ; but that the animal and vegetable alkaloids
are simUar in their chemical constitution, and that they
are both products of albuminous or proteid decomposi-
tion ; and that some ab least of the so-called ptomaines
•are identical with vegetable alkaloids. f

"We may now indeed regard alkaloids," writes Dr.
Brunton in the third edition of his valuable work on
Pharmacology, " as products of albuminous decomposi-
tion, whether their albuminous precursor be contained
in the cells of plants and altered during the process of
growth, or whether the albuminous substances undergo
decomposition outside or inside the animal body, or

♦ Dr. A. M, Brown, he. cit.

t Dr. Lauder Brunton in "Practitioner," vol. xxxv., 1885,
" Poiaons formed from food," also " Disorders of Digestion," p. 222,
1886.

8

Tlie Animal Alkaloids.

by processes of digestion as by unorganised fer-
ments."*''

It has been also shown that the alkaloid products
formed by the i)utrefaction of albuminous substances
vary according to the stage of decay at -which they are
produced. At first the poisonous action of the pto-
maines may be slight ; but as decomposition advances
the poisons become more vh-ulent, while after a still
longer period they become more broken up and lose to
a greater extent their poisonous power (Brunton).

The poison muscarine which had only been known as
obtainable from a plant, (the Agaricus muscarius, " fly-
fungus ") has been discovered by Brieger to be a pro-
duct of the decomposition of fish ; and it has also been
made synthetically by Schmiedeberg and Harnack from
choline.

It is further to be noted that some of the products of
decomposition thus obtained are found to be poisonous,
and that others are not so ; that among the poisonous
ones various degrees of activity prevail, some being but
slightly poisonous, whilst others are most vu'ulent ; —
also that while many retain their properties for a
length of time, yet when mixed or in combinations
(still uncertain) they further decompose or neuraUze
each other, appearing to have an antagonistic action
the one to the other, and so become inert. Brieger,
for example, has obtained from decomposing albuminous
substances several well-defined chemical bodies. f From
flesh he has got a substance which he calls " neuridine"
which is innocuous, and another substance " ncunne"
which, however, is poisonous, while the *^ muscarine"

* " Pharmacology and Therapeutics," p. 100.

t Brieger, " Ueber Ptomaines," Berlin Klin. Wochenschr, 1887.

Poisonous Nature of " Extractives."

9

from fish is more poisonous still. Two other substances,
one " ethyle7iediamine " is poisonous, while "gadenine"
is not poisonous. He has also obtained from human
corpses a different set of bodies, one of which he calls
" cadave7ine," and the other " putrescine which are
but feeble poisons ; while two others " madeleme " and
" sepsine " which are produced later on in the decom-
position are much more powerful poisons — causing
paralysis and death. From decomposing albuminous
substances he has obtained many other well-detiued
chemical bodies ; as well as some substances to which
no names have yet been given.

In addition to these alkaloids obtained by Brieger, a
number of poisons have been got by other workers from
decomposing articles of food or from dead bodies, and
even from portions of healthy animal bodies. And
although these may not have been obtained in the
same state of purity, nor have had their chemical con-
stitutions so well-defined as Brieger's, they are still, as
unknown " extractives " {x, y, z's), of great interest and
importance.

The physiological action of these alkahne bases of
animal origin do not present the diversity of action
which has given to the study of vegetable alkaloids so
much interest.

Nevertheless the physiological effects of the ptomaines
and the leucomaines are powerful enough to compare
with those of " mtcscarine," " ciirar-e," "nicotine," and
other very active and virulent vegetable poisons. In
support of this view a series of investigations and ex-
periments have shown that the primary products of
albuminous decomposition of digestive ferments, such
as peptones are poisonous. Brieger has recently shown

10

The Animal Alkaloids.

that pepsine will split up albuminous substances still
furtlier, so that by digesting fibrine with artificial gas-
tric juice, he obtained an alkaloid to which he has given
the name of "peptotoxi7ie."

The bitter taste which sometimes appears during the
digestion of meat, or of milk artificially, as Dr. L.
Brunton has pointed out, is suggestive of the formation
of some alkaloid, although it has not yet been deter-
mined what this bitterness really depends on ; and Dr.
Lauder Brunton further gives the timely and much
needed caution against the extreme and indiscriminate
use of the various digestive ferments, and of the many
varied artificially digested foods which have now be-
come so common. From this point of view a study
of the products of albuminous decomposition has
become of much practical importance, not only as
regards pathology, but as regards therapeutics, for " it
is possible that digestive ferments hke other powerful
agents may be edged tools, and capable of doing harm
as well as good."

Ever since 1877, one ptomaine after another has
been discovered, each fresh observation making the
course of their origin more clear, until at last in 1885,
Gautier made the crowning discovery regarding the
formation of leucomainee in the vital ceUs of the body.
His researches extending from 1881 to 1886, show that
the animal alkaloids are a necessary product of vital
physiological processes, he having obtained fi"om the
secretions of living beings alkaloid bodies having poi-
sonous properties — results which have been confirmed
by M. Peter.

They have shown that about four-fifths of our
disassimilations are the result of transformations

Their Continuous Formation.

11

within the body, comparable to the oxidation of alco-
hol; and that the remaining fifth of the disassimi-
lations are formed at the expense of the Hving
tissues themselves "free of all demands on foreign
oxygen." In other words a fifth part of our tissues
Uve after the manner of ferments ; that is, they are
anaerobious or putrefactive as to their life. Hence
the possibility of alkaloids being thus formed within
the hving organism, independent of bacterial fermenta-
tion is quite within our conception.

" Every instant of our lives, do we not elaborate
normally and in the physiological processes of our
existence, acids and bases, not merely carbonic acid,
but uric acid— the latter a product of animal Ufe whose
normal production is inconceivable apart from it,
although it may have been formed synthetically? " The
yearly increasing number of so-called organic bodies,
which until recently were regarded as the outcome
solely of life-processes, but which chemists have suc-
ceeded in building up synthetically, compel us to admit
that the hne between organic and inorganic matter is
an arbitrary limit interposed by defective knowledge.
If certain organic bodies can be built up synthetically,
without the aid of vital forces, it is not unreasonable to
beheve that variations in the character of life-processes
may be effected by the purely physical action of basic
products formed within the organism. This is all the
more easy of acceptance, since it is admitted that these
by-products are the result of that form of chemical
action at present inseparable from 'hfe.'"* Do we
not also spontaneously and normally fabricate bases
such as urea — a most complex product — which can

* Dr. J. Dixon Mann, "Medical Chroniole," March, 1888.

12

The Animal Alkaloids.

combine with azotic (or nitric) and oxalic acid ; and
■which by sphtting up chemically may go to the formation
of carbonate of ammonia ? In the face of such poten-
tialities may we not admit that the living organism is
capable of fabricating various alkaloids.*

Bio- chemically, such a capacity has been proved to
demonstration, and therefore it is probable that poi-
sonous alkaloids are continuously being formed in
healthy men and animals by the decomposition of
albumen in the intestinal canal, during the process of
digestion or in the blood and tissues generally by the
metabolism which occurs during the functional activities
of life. A considerable portion of these alkaloids is in
all probability destroyed in the body, and some are
excreted in the urine and fasces, from both of which
powerful poisons have been extracted.! Moreover, " a
considerable production of alkaloids takes place in the
intestine, both when the digestive processes are nor-
mal and more especially when they are disordered ;
at the same time alkaloids are being formed in the
muscles, and possibly also in other tissues. Were aU
the alkaloids to be retained in the body, poisoning
would undoubtedly ensue, and Bouchard considers that
the alkaloids formed in the intestine of a healthy
man in twenty- four hours would be sufficient to kill
him if they were all absorbed and excretion stopped.
He finds that the poisonous activity of even healthy
human faeces is very great, and a substance obtained
from them by dialysis produced violent convulsions in
rabbits. When the functions of the kidney are im-

* Dr. A. M. Brown, Zoc. cit.

t Dr. Lauder Brunton, " On Disorders of Digestion," p. 283.

Continuous Formation of Animal Alkaloids. 13

paired so that excretion is stopped, urasmia occurs, and
Bouchard would give the name of stercor£emia to
this condition, because he believes it to be due to
alkaloids absorbed from the intestines. He also thinks
that the nervous disturbance which occurs in cases of
dyspepsia is due to poisoning by ptomaines."*

But long before Armand Gautier's Memoire was pub-
lished in the "Archives of the Academy of Sciences of
Paris," evidences of the existence of a physiological
function in the animal economy were not wanting as to
its power of elaborating alkaloids during life.

Liebig and Pettenkofer had long made known the
existence of " kreatinine" in urines — a product of
animal origin possessing properties clearly alkaloid.
*' Kreatine " was soon after detected in the animal tis-
sues resulting from kreatinine. Twenty years later,
Liebreich detected the vegetable alkaloid ' ' hetaine ' ' in
human urine ; and so recently as 1880, Pouchet has
recorded the presence of " karnine " and an alkaloid in
well-defined crystals, concerning which Gautier has not
only confirmed the fact, but also that the alkaloid
possesses the properties of a ptomaine. In 1880, by
carefully operating with glands of snakes, he was en-
abled to eliminate material from them of an alkaloid
nature ; and from the cobra he obtained two new sub-
stances, each of the nature of a ptomaine.

From this time onwards, the study of a new class of
alkaloids, the products physiologically of animals during
hfe, has steadily progressed, and this preliminary ad-
vance was further strengthened when in 1882 Bouchard
disclosed the fact that not only were alkaloids present

* Dr. Lauder Brunton, "Pharmacology and Therapeutics," 3rd
edition, p. 101.

14

The Animal Alkaloids,

in appreciable quantities in normal urine, but that they
augmented notably in the course of certain maladies —
in typhoid fever for example. And this applies to a
still wider pathological area, so that, generahsing the
facts "we already know, we venture to conclude that in
the course of certain maladies these poisonous products
of the urinary secretion notably increase in quantity,
until a crisis is reached when they again diminish and
finally disappear (Lepine, Guerm, Aubert, A, M. Brown,
Lauder Brunton).

Thus, the incessant elaboration of alkaloid products
formed at the expense of proteid elements, precisely as
urea and carbonic acid are similarly and simultaneously
formed, is now fully confirmed ; and to distinguish this
class of products from that of the cadaveric alkaloids or
^' ■ptomaines,'" Gautier has named them " leucomdines"
or alkaloids derived during the processes of life from
the decomposition of albuminoid substances.

Gautier has further shown that there is a distinction
to be appreciated between alkaloids formed during the
bacterial destruction of albuminoids, and alkaloids which
owe their formation to the bio- chemical and physio-
logical activities of the normal tissues. He asserts
that oxygen is not the only cause of these transforma-
tive processes, but that nearly one-fifth part of the life
of the larger animals is what Pasteur has termed
" anaerobic" — that is to say — deriving its force-vitaUty
from internal modifications brought about independently
of the help of oxygen, and with the resulting formation
of the " leucomaiues." Pasteur's researches, as well
as those of other scientific observers, have shown that
anaerobic life is a characteristic of the lower orders of
bacterial ferments ; and that oxygen is not essential to

Discovery of Netv Leucomaines.

15

their existence. And just as the vital cells elaborate
"leucomaines," so these bacterial ferments, feeding on
the albuminoid substances of the body and causing
what is known as putrefaction, develop "ptomaines"
as then- waste products. But however important this
distinction may be, it does not support the view that the
ptomaines and leucomaines are distinct or opposed to
each other. On the contrary, it is impossible to trace
the hmits where the one series of alkaloids begins or
the other ends ; and there are a certain number of
known alkaloids which are common to both series.

Gautier has recently also announced the discovery of
five new ^^leucomaines," namely, "adenine" from the
pancreas, and one from the spleen,* the other three
resulting from experiments on the muscular juices of
the higher animals. The second body isolated from the
spleen by Morell, has a paralyso-motor action, with a
powerful effect on the medulla oblongata.!

The late Dr. L. 0. Wooldridge (whose early death is
so much to be deplored) found that a remarkable in-
toxicant proteid could be prepared from the thymus or
testicle ; and that when this was injected into the veins
it produced widespread clotting in the vessels. |

They all exhibit simpler chemical formula than vege-
table alkaloids for the most part do ; and a number of
the leucomaines have been manufactured synthetically.

Dr. A. M. Brown § gives us a classification of these
"new physiological alkaloids " with then: sources, based
on that of Dr. Hugounenq, of Lyons, in the following
groups : —

» Hoppe-Seyler's "Zeitschrift," March llth, 1886.
t "The Lancet," April 24th, 1886.
X " Proceed. Eoyal Society," 1886.
§ Loc. ext., p. 5.

10

The Animal Alkaloids.

I. The Ubic Leucomaine Group.— Betaines.

Betaine is the representative of this group, having

(CH') = N — 0
the chemical formula of H" N0^= |

CH"— CO.

The base was originally discovered in beetroot in
1866 by Scheifler, and in 1869 Liebreich detected its
presence in human urine.

Karnine, CWWO^. — Commences the natural series
of alkaloids of the uric groups. The base was isolated
from imported meat by Weidel, and afterwards in yeast
waters by Schutzenberger.

Adenine, C^WW. — Discovered by Kossel in 1885.

Guanine, C^WWO. — Discovered in 1884 by linger,
and since met with in a great number of products of
animal nature in the flesh, the organs, and the excre-
mental matters of certain mammifera, in fowls and
fish, and also in certain plants.

Sarkine or hyijo- xanthine, C*H*N*0. — Found in cer-
tain plants, but for the most part in animal tissues.

Xanthine, O'WWO^.—ls widely distributed in the
organism, in almost all the liquids and tissues of the
animal economy from the splitting up of nucleine. The
base was first isolated by Marcet in 1819.

Psmdo-exanthine, C*H^N'0. — Discovered by Gautier
in the muscular tissue of the higher animals.

These last four leucomaines form a distinct group
as to community of origin, with analogous chemi-
cal properties : — (1) They all possess a combination
(C^H^N^) of a remarkable stability, analogous in certain
respects to the stabiUty of the pyridic compounds. (2)

The Kreatinine Leucomdines.

17

They can all give up cyanliydric acid, and two of them,
xanthine and hypo-exanthine, may be obtained syn-
thetically in operating with the same cyanhydric acid.
(3) All of them are derived from albuminoid substances
by reactions which are identical in origin. (4) Three
of them present in a high degree that insolubility in
water the pyridic compounds exhibit.

Dr. Brown further notes the startling fact " that
the most terrible poison, cyanhydric acid, forms the
chemical skeleton of that cellular nucleus which is the
most active phenomenon of vitaUty."

II. The Kreatinine Leucomaine Group.

That well known base kreatinine, C^H'N^O* NH=

NH — CO

C< ! I
N (CHa) — CN,

heads the list of the other new alkaloids discovered by
Gautier since 1881. They are aU of fresh meat origin.
Kreatinine was discovered by Liebig in the action of
chlorohydric acid on kreatine, and Pettenkofer after-
wards found it in human urine.

Xantho-creatinine, G^WWO. — The most abundant
of these bases is of cadaveric odour, soluble in cold
water, and with a strongly alkaline reaction.

Crusocreatinine, C^H^N^O. — Possessing the general
properties of kreatinine which it strongly resembles in
chemical elements and alkahnity.

Amphicreatine, CH^^N^O. — Corresponds with two
molecules of kreatine plus CNH groupment, thus
having the closest analogy to kreatine, although the
formula seems widely to differ from it.

18

The Animal Alkaloids.

III. An Unclassified Group — According to thkir

Sources.

From the urine. — A uride — allantoine — and a base —
karnine — already known, a second alkaloid Las been
discovered with the formula C'H^N^O^

From the blood and important viscera. — Alkaloids have
been met with in appreciable quantities.

From the breath. — Du Bois-Eaymond has obtained a
poisonous alkaloid which he has named "Anthro-
potoxine."*

From thymus or testicle. — A proteid intoxicant by Dr.
Wooldridge.

From the spleen. — M. Morel, of LUle, has obtained an
alkaloid isolated in dehquescent crystals.

From the intestines. — A base which seems to belong to
the pyridic group isolated from choleraic dejections.

From the saliva. — Gautier has determined the exist-
ence of an alkaloid in human sahva.

The venoms of certain snakes and hatrachians as well as
from certain mollusca and fishes. From this latter class
Breiger has identified an active princi]3le in the mytiloxin
and given its formula as Cff^NO^.

So much for the purely bio- chemical aspect of these
researches ; let us now consider : —

2. The clinical, pathological and practical aspects.

As to the poisonous character of both ptomaines and
leucomaines there is no doubt ; for when injected into
birds and other animals even an extremely minute dose
has been sufficient to cause death. Moreover, the
symptoms, which preceded death in these experiments
were thoroughly characteristic of poisoning by putrid
♦ "Lancet," April 6th, 1889, p. 710.

Their Pathological Relations.

19

animal matter ; namely diarrhoea, intestinal inflamma-
tion, dilatation of the pupil, loss of muscular power and
convulsions.

According to the different sources of poisoning or in-
toxication (as it is technically called), there are corres-
pondingly different indications, signs, or symptoms
capable of classification as below : — (1) Poisonmg by
the " Extractives " is attended by hyperthermia. (2)
Poisoning by the " Animal alkaloids " is accompanied
by hypothermia. (3) A combination or succession of
hyperthermic and hypothermic phenomena may become
manifest, according to the combination or alternation
of poisoning by the deleterious physiological products,
or theii- antagonistic action. (Dr. A. M. Brown).

Some of the clinical facts may thus appear to be
contradictory or inconsistent ; for in certain cases (so-
called urfemia for example) there is to be observed an
elevation of temperature ; while in certain other cases
the temperature may be normal ; and in others it may
fall. But once it has been determined that when " ex-
tractive matters " accumulate in the blood we detect
hyperthermia ; on the other hand if " alkaloids " accu-
mulate we have hypothermia ; while if the two factors
co-exist they may neutralise each other, or become an-
tagonistic in their action, so that temperature may re-
main stationary or normal. But should one or other
of the factors predominate, immediately the scale is
turned, so that some variation may be noted. Thus,
the balance of metabohc changes gives unmistakable
evidence of a nitrogenous residuum which is morbid.

There is in these researches still further disclosed the
fact that in this auto-infection, this spontaneous or self-
infection of the living organism by the " alkaloids " and

c2

20

The Animal Alkaloids.

" extractives " of its own formation there is no question
of quality, but simi3ly one of quantity to be considered,
by reason of the essential physiological source and ac-
tion of the poison. Many of the phenomena which
manifest themselves in disease seem best capable of
explanation on the supposition of the presence of some
autogenic toxic agent circulating in the blood, and thus
producing a specific effect on the tissues. In other
words, the healthy hving organism may become poi-
soned (gradually and more or less slowly), by the
accumulation within itself of deleterious substances
normally elaborated, but imperfectly or defectively
eliminated. Hence the slow and insidious onset of
much ill-health ; and from which recovery is corres-
pondingly slow. I might here instance all the " con-
stitutional " diseases of which rheumatism and gout
are typical representatives. " They are such diseases
as become developed under the influence of agents
generated within the body itself through the continuous
exercise of its functions in the daily course of nutri-
tion, development and growth."**

An important aspect of the question now presents
itself for solution; namely: — "in what way does this
auto -infection or spontaneous poisoning of the system
take place ? "

This is a very complex question, and as Dr. A. M.
Brown observes, it can only be understood and ex-
plained by the mode in which we regard the pheno-
mena of life. Life is undoubtedly an active state, the
result of the combination of many physiological pro-
cesses, in the concurrent exercise of the bodily functions
which are essentially relative and contingent on one

* " Science and Practice of Medicine," 7tli edit., vol. i., p. 829.

Formation of Extractives.

21

another, implying at the same time a series of partial
and local deaths. Thus, it is that our organism lives
on conditions of incessant elementary disintegrations,
so that " we constantly bear about within us the effete
debris of our living selves."

Health must therefore always, and can only be a
phenomenal phase of hfe which is relative and con-
tingent ; life's equihbrium between the rough and the
smooth ; the ease and unease ; the good and the evil ;
when the vital functions are performed in a united and
harmonious manner which experience has taught us to
regard as normal; and as the "wholesome unity which
constitutes health."*"'

Hence normal health comes to be conditional on an
incessant formation, transformation and ehmination of
the effete or old organic materials which must give
place to the new. It is this effete material in (whatso-
ever form it is found) which, therefore, represents a
series of partial deaths ; and which as the result of
organic functional operations, constitutes life, during
which the tissues and organs in the processes of their
metabohc changes, perform a constant function of disin-
tegration— fabricating during these processes those
"alkaloids" and "extractives" — "those x, y, z's of
pathology" which must be regarded as veritable
"scoria" (Brown) or " ■physiological ashes" (Lauder
Brunton) resulting from the processes of combustion in
the elements of organic tissues. For the processes of
hfe have been likened to a slow continuous burning ; so
that fresh fuel in the form of food, must be frequently
added to supply the place of the waste material which
the burning process entails. In every living cell which

» " Medical Pathology," by U. G. Sutton, 188G, p. 2.

22

The Animal Alkaloids,

makes up the animal body, there thus goes on a con-
stant transformation of energy, thereby inducing cer-
tain modifications of the material substance of the
cells — the prime mover in the process being oxygen,
"which by acting on the material of the cell burns it up,
at the same time giving off material which if not cast
out of the system would poison it and ultimately de-
stroy its hfe.

And it will further appear in the following pages
that "the vital processes are much more readily ar-
rested by the accumulation of waste products within
the organs of the body than by any want of nutriment
of the organs themselves."*

Thus is it, that our organism is constantly dying ;
and strange as the paradox may sound, we cannot live
unless it does die. How precarious therefore is the
condition we call health ; and how by the simple accu-
mulation of cadaveric material disease may manifest
itself 1 How scientifically and also prosaically Uteral
do the truths stand out that " in the midst of life we
are in death ; " and that " as we begin to hve, so we
begin to die ! "

Then comes another important question ; namely,

how do we resist the constant auto-infection to which
we are thus constantly exposed ?

In reply to this we may say that there are two
physiological modes or vital mechanisms as constantly
at work in our bodies for our protection. These are —

(1) the elimination of the toxic products as excretions
by the various emunctories, the liver, the kidneys, the
skin, the lungs and the intestinal mucous membranes ;

(2) the destruction of the toxic products by oxygena-

* Dr. Lauder Brunton, loc. cit., p. 237.

Pathology of Fatigue- Fever.

23

tion ; wliicli consists in a continuous combustion of
the leucomaines by the oxygen of the blood, in
which they are burned or consumed in its current, or
partially in the tissues and organs.

On the other hand also we know that their accumu-
lation may take place under two widely different condi-
tions : as when there is an excess of " extractive
matters " and " alkaloids," with normal but inadequate
ehmination by the emunctories : or, the production of
the deleterious materials being normal, their elimina-
tion is inadequate from disease or derangement of the
emunctories.

Hence auto-infection may result from excessive pro-
duction, and inefficient {i.e., inadequate) elimination,
the emunctories remaining sound, a condition which is
constantly seen in all forms of physical over- taxation
or over- exertion, as in a prolonged march, or by exces-
sive drill, especially in young and adolescent soldiers.
Of such examples Army Medical OflBcers acquire con-
siderable experience.

In a paper recently submitted to the Accademia dei
Lincei (to be printed in its Transactions) the physiology
of fatigue has been carefuUy worked out by Professor
Angelo Mosso of Turin, with a view to the determina-
tion of the pathological manifestions which accom-
pany that physical condition. He has found that when
fatigue is carried beyond the moderate stage, at which
it is decidedly beneficial, the blood is subjected to a
decomposing process through the infiltration into it
of substances which act as poisons — substances which
when injected into the circulation of healthy animals,
induce malaise, and all the signs of excessive exhaus-
tion. It was on the soldiers of the Italian Army that

24

The Animal Alkaloids.

Mosso's experiments were made ; and lie has convinced
himself that he has arrived at practical results, which
might be formulated in regulations, as to the amount
of exertion to be put forth on the march, as to the best
distribution of the halts and of sleep, and as to the
lightening of the weight which each soldier has to
carry.

Meanwhile M. Peter gives us the following illustra-
tion of this auto-infection as observed by him in the
wards of the illustrious French physician M. Chomel,
his teacher. Under the Professor's charge there came
a young man apparently suffering from great prostra-
tion, muscular pain and spine-ache. Chomel made his
examination with great care and attention ; and in the
presence of his patient, he gave his diagnosis in Latin,
which was " Aut febris Pey erica, aut variola incipiens" —
typhoid fever or incipient smallpox — a diagnosis which
seemed so little precise, pronounced by one so eminent
in his art, that it surprised somewhat and dissatisfied
his inexperienced pupil. But Chomel was not then
aware of certain antecedent factors which had brought
about the ailments of his patient. The young feUow,
in a state of destitution, had walked from Compiegne
to Paris in two days, sleeping by the wayside at night,
and nourishing himself with such refuse food as chance
supplied. Under these circumstances the patient de-
veloped febrile symptoms, from the excretory products
of his metabolism having accumulated in his system
and disturbed it. But the day after his admission (and
simply from rest in bed) he felt better ; and the day
following he was altogether well. Simple rest had en-
abled the muscular system and the constitution gene-
" "Laucet," June 25, 1887, p. 1295.

Patholo(/y of Fatigue-Fever. 25

rally to rid itself of the proteid embarrassment resulting
from the functional destruction of the tissues. His
ailment was entirely due to "the fever of over-taxation"
or "of over- exertion," brought on by accumulation in
his system of material elaborated in excess and in-
efficiently (or inadequately) eliminated. Thus, a tem-
porary poisoning of the system had lit up " the fever of
prostration ; " and hence the hesitating diagnosis of
the illustrious physician which length of time cleared up.
, This " fever of prostration " engendered by over-
exertion is a very characteristic one, due to the proteid
embarrassment which results from the functional dis-
tm-bance of the tissues. In the process of fatigue, the
weak link is at the junction of nerve with muscle,
where we have an effect similar to that brought about
by the action of curare and the result of degeneration.*
The changes which take place (chemical and functional)
although they cannot be actually seen, yet to some
extent they can be measured, judged of and made out,
or reahsed from their effects. The extent of the
metabohsm may perhaps be best appreciated from such
records of experience as Mr. Maclaren, of Oxford, has
given in his very interesting work on " Training." -f
"Du ring a long pedestrian tour, exceeding nine hours
daily (equal to a long march) with a knapsack of
twelve pounds, the chest measurement fell from 41
inches to 39^ inches ; the upper arm from 14^ inches
girth to 13f ; the lower arm remaining unchanged at
12^. The lower Umbs on the contrary, were vastly in-
creased ; the calf of the leg passing from 16 inches to
i7i, and the thigh from 23^ to 25 inches."

♦ Waller in " British Medical Journal," July 2oth, 1885.
t Page 13, note.

26

The Animal Alkaloids.

Let us now analyse the conditions of M. Chomel's
patient a little further in the light of more recent
knowledge regarding the metaboHsm of the body. We
know that certain medicinal agents are cumulative in
their action, e.g., digitaline and strychnine; so also do
we know that " extractives " are similarly accumulative
in the system after their elaboration. Let us suppose
that in this given case the elaboration of the " ex-
tractives " and " alkaloids " in this young lad's body is
represented by 10, and that their elimination is repre-
sented by 8 ; we have then a storing up or accumulation
of these " extractives " to the extent of 2 per day of
auto-infective elements. But suppose his walk had
been much longer, and that it had extended over 20
days instead of 2 ; then instead of storing up twice 2,
he would have stored up twice 20 ; and instead of a
comparatively simple or mild attack of the toxic " fever
of prostration " or of " febrile symptoms from over-
exertion " — an auto- infective fever of short duration —
he would have suffered from a febrile intoxication more
complete, more persistent, and more serious. He would
in all probability have developed a form of typhus, such
as has been known to occur in soldiers on a long and
harassing march, of which there are many instances in
the European campaigns of the latter half of the last
and beginning of the present century.

But in the typhus of armies another important factor
(besides over- exertion) intervenes which must also be
reckoned with, and that is the massing together of
large bodies of troops, and all that must result from
this. The noxious effects of air in places where many
persons have been breathing, have been attributed
hitherto to carbonic acid ; but recent experiments con-

Pathology of " Typltusation."

27

ducted by capable observers sliow that this is an error,
or at auy rate, an insufficient explanation. It has
been found that air copiously impregnated with pjtre
carbonic acid can be breathed with absolute impunity ;
but that air spoiled by the breathing of human beings
contains small quantities of one or more extremely
poisonous substances, which Du Bois-Eaymond has
named " anthropotoxine," and to which alone the
noxiousness of air in unventilated rooms is due. The
most recent experiments show that these poisons came
from the lungs.'* Hence the typhusation of one man
by the many comes into play ; and this having taken
place, there is no reason why the subject in whom a
fever is generated, may not communicate it to his
neighbour. In this connection it is further worthy of
note that an alkaloid resembhng atropine in its action
has been separated by Sonnenschien and Zuelzer from
decomposing animal matter ; and that this alkaloid has
also been found in the bodies of persons dying from
typhus fever. f

And further in relation to tissue waste it is not to be
forgotten that the products of the functional activity of
an organ are not only poisonous to itself, but may be
poisonous to other organs. Thus the waste products of
muscular activity gradually poison the muscle and
prevent its contractions. Lactic acid which is a pro-
duct of muscular waste is poisonous not only to muscle,
but to some extent to nerves, while it ialso lessens the
functional activity of the brain and produces sleep.

Making aU due allowance, therefore, for the massing

' " Lancet," April 6th, 1889, p. 710.

t "Pharmacology and Therap3Utics," by Dr. Lauder Brunton.
p. 8L

28

The Animal Alkaloids.

together of men in large bodies, we may recognise Low-
in tliis way the typhus of armies and camps may under
special conditions originate de novo and spread, so that
the men become poisoned by their own exhalations.
" No less an authority than Virchow has endorsed the
opinion that the poison of typhus can be brought into
existence by the concurrence of such conditions as are
here described. The late Dr. Murchison, of London,
and Dr. Hudson, of Dublin, have maintained similar
views."*

It is therefore scarcely possible to escape the convic-
tion that there exists a morbid or pathological series of
ailments which naturally lead from the simple form of
"fatigue fever' or "fever of prostration " (such as after
a long march) up to that of the more deadly typhus,
which is thus the highest expression of the poisoning of
the organism by itself or by contact with others under
conditions such as are now referred to.f War and
typhus fever have thus always gone together, and the
mihtary medical officers of former days were wont to
recognise this form of typhus spontaneously developing
itself in the continental campaigns. Its origin, they did
not doubt, recognised prolonged fatigue, overcrowding,
and privation generally as antecedent factors in its
causation ; and they no more questioned its appearing
sj)ontaneously then its contagiousness. Observation
and experience alike forced them to admit the view
(once recognised as inconsistent) that such fevers might
be at once spontaneous in origin and contagious as to
propagation. The history of aU typhus epidemics
shows that it is essentially associated with overcrowding

* See Fagpe's "Principles and Practice of Medicine," vol. i., p. 144.
t Dr. A. M. Brown, loc, cit.

De Novo Oncjin of Typhus.

29

and destitution, with the fouHng of the air by the
concentrated emanations of hving bodies, so that the
atmosphere became unfit for respiration from its
closeness and pollution by aerial filth and overcrowding.
These are the combination of factors under which
typhus fever is generated. Its origin de novo thus
reads as a progressive development especially in asso-
ciation with the putrefying products of animal exhala-
tions and the excrementitious matters of diarrhoeal and
dysenteric cases, an origin strongly substantiated by
more recent experience as well as by the records of
campaigns and war pestilences long gone by, but which
we can now read in a different way from heretofore,
and interpret by the hght of knowledge more recently
acquired.

The idea that " the source of all typhus matter is to
be looked for solely in concentrated human effluvia " —
the idea that overcrowding in filthy and unventilated
rooms affords the essential condition for the develop-
ment of typhus foci and for the spread of the disease
therefrom, has been completely borne out by the experi-
ence of all time.* The mode of origin of sporadic
cases in the absence of any epidemic, and of outbreaks
in public institutions and amongst isolated bodies of
men, furnishes the more conclusive evidence of typhus
arising de novo. The fever known as jail fever was
undoubtedly typhus, and many observations show that
it originated in the prisons from overcrowding and
deficient ventilation. The prisons then became the
principal foci whence the disease spread, and the story
of the various " black assizes " (six in number), in
which prisoners brought up for trial gave typhus to the
* Cheyne, "Dublin Hosp. Reports," 1818, vol. ii., p. 53.

30

The Animal Alkaloids.

judges, counsel, and jurymen, is full of pathological
interest, especially, as Lord Bacon observed, " that the
prisoners were not suffering from typhus themselves."
The cu-cumstances under which the fever appeared in
jails and prisons in this country and on the continent
were always the same, and to the exclusion of every
conceivable source of importation.* On shipboard its
origin de novo has a similar history ; and with regard to
war pestilences, its origin has invariably been due to
overcrowding, with bodily and mental depression. It
has also been especiaUy noted that in many parts of
the continent of Europe, where typhus never occurs in
time of peace, it became epidemic in time of war.
Similarly, it has originated in overcrowded and badly
ventilated hosiaitals, and then it was originally described
as "hospital fever" by Sir John Pringle, who pubUshed
" Observations on Diseases of the Army," 1768. t

Down to the commencement of the present century
no doubt existed as to the spontaneous origin de novo of
typhus fever. Lord Bacon thus expressed his behef :
" The most pernicious infection, next to the plague, is
the smell of the jail, where the prisoners have been
long and close and nastily kept, wherein we have had
experience twice or thrice, when both the judges that
sat upon the bench, and numbers who attended the
business, sickened upon it and died." And the opinions
of the great physicians of the past were to the effect
that vapours were constantly being exhaled from the

» Murchison, "Treatise on Continued Fevers," 1st Edition, p. 106.

t A contagious fever similar to typhus has been known to occur
amongst animals on board ships in which they were crowded in tran-
sit from England to America during the American War (Murchison,
loc. cit., p. 111).

Connection between Dysentery and Tyjihus.

31

human body— that such vapours were subtle, acrid,
and offensive to the smell ; when retained in the body
it became morbid, and if re-absorbed by the body they
were highly deleterious. If a number of persons, there-
fore, are long confined ua a close place, not properly
ventilated, so that they inspire and swallow with their
spittle the vapours of each other, they soon feel its bad
effects. Bad food, nervous depression, add to the
misery, and soon the seeds of a pestilential fever arise,
dangerous to themselves and to others ; and once
produced, the fever easily spreads by contagion.*

The connection between yeUow fever and the dysen-
teric, and other discharges of the negro body, is only a
part of that general connection between dysentery and
typhus, which has so pronounced a history in famines
and war pestilences. The subject is full of pathological
interest, and requires more investigation, especially as
to the connection between dysentery and other diseases
such as tyj)hus fever, and in relation to animal alka-
loids. There is evidence to show that these diseases are
sometimes vicarious — dysentery in the dark races,
taking the place of typhus in the white man. The
disease which carried off the miserable negroes in the
crowded holds of the slave ships was dysentery and not
typhus ; but out of the dysenteric corruption and putre-
faction typhus fever sprung : and there is much
evidence to show that the active generating cause is
some highly ammoniacal compound. The existence of
ammonia in the blood has long been believed to account
for the phenomena of typhus. Dr. Richardson has
shown that ammonia introduced artificially into the
blood " produces typhoid (or typhus- like) symptoms;"
* Grant (1775), quoted by Murobison, loc. cit.

32

Tlie Animal Alkaloids.

and the late Dr. Murchison''' sums up the argument,
from his own personal extensive experience in the
London Fever Hospital, in the following words : —

"In severe cases of tyj)hus, not only is there reason
to believe that the blood is ammoniacal, but the exhala-
tions from the lungs and skin, and the discharges from
the bowels, contain a large amount of ammonia. It is
a common observation that a pungent ammoniacal
odour is given off by the skin and lungs in typhus,
while the presence of a large quantity of ammonia in
the breath admits of actual demonstration. It has also
been ascertained that the cases in which the odour is
strongest, communicate typhus most readily to persons
in health ; and in many of these cases where the sym-
ptoms of typhus have supervened immediately on
exposure to the source of contagion, and where we may
suppose the poison to have been unusually concentrated,
the affected persons have been conscious, at the time of
exposure, of a most disagreeable odour, pungent, and
ammoniacal."

Hence, we may expect to find the origin of typhus in
some physiological disorder of the ammonia-producing
function — some relation between the common aberration
of the functions producing ammonia in health and the
self-existent specific infective disease known as typhus.
Its spontaneous origin may be in this way physiologi-
cally explained. The experiments of chemists show
that ammonia is contained in the cutaneous exhalations
in health, and minute traces of ammonia are constantly
being exhaled in healthy respiration. And although
the quantity may be much smaller than in typhus, it is
probable that, when a large number of human beings

* hoc. cit. p. 114.

Formation of Ammonia Products.

83

are crowded into a small unventilated place, the
ammoniacal exhalations are much increased and con-
centrated, and that by this putrefaction typhus fever is
generated. Here we have another example as to how
the hving tissue elements of the body itself play an
important part in the elaboration of disease.* The
first effect of over-crowding with no ventilation is to
cause the respnation to go on in an atmosphere charged
with impure carbonic acid ; and it has been shown by
experiment that even a small percentage of carbonic
acid in the respired air is sufficient to leave a serious
diminution in the amount of carbonic acid thrown off,
and of oxygen absorbed, with the result " that those
oxidating processes which minister to the elimination
of effete matter from the system must be imperfectly
performed, and that an accumulation of substances
tending to putrescence must take place in the blood.
Hence, there will be probably a considerable increase in
the amount of such matters in the pulmonary and
cutaneous exhalation."! The unrenewed air thus
becomes charged, not only with carbonic acid, (which
per se and pure has been shown by Du Bois-Eaymond
to be harmless), but also with organic matters in
a state of decomposition, of which the chief pro-
duct is ammonia. When we consider also the exis-
tence of compound alcoholic ammonias, and with
their powers as poisons, we cannot fail to see how
such or allied bodies may arise within the system,
though we may not yet be able to trace the pro-
cesses. These ammonias have a near co-relation to

• Surgeon-Major Dr. T. E. Lewis, loc. tit.

t Dr. W. B. Carpenter, " Human Physiology." Fifth edition,
p. 301.

D

34

The Animal Alkaloids.

the cyanogen compounds — themselves derivatives of
ammonia.*''

The nominal quantity of ammonia contained in the
breath is exceeded in other diseases besides typhus, a
circumstance which may account for the spontaneous
progressive evolution of typhus fever in unventilated
hospitals under circumstances of crowding insufficient
to generate it elsewhere ; and also for the observation
that a deteriorated state of the constitution predisposes
to the development of typhus.

" From the present state of our knowledge, therefore,
it seems not unreasonable to conclude that the disagree-
able odour of the cutaneous and pulmonary exhalations
of typhus patients, as well as the offensive smell gener-
ated by over-crowding are due to one and the same
source, namely, some unknown compound of am-
monia, "-j-

It appears to me, therefore, that like erysipelas and
diphtheria, the weight of evidence and of argument is
in favour of the occasional de novo origin of typhus
fever by " progressive developments," through as yet
unknown and undetermined concurrent factors in the
surroundings of the patient ; his environment in the
widest sense of the term, and that such de novo origin
of these diseases does not exclude the possibihty of
their subsequent spread by contagion." |

What is true of "fatigue fever" and of "typhus
fever," is equally true as regards typhoid. Mihtary

* "A Sketch of an hypothesis towards vito-chemical methods in
Pathology and Therapeutics," by W. H. Pearse, Esq., M.D., in
" Prov. Med. Journal," 1888.

t Murchison, loc. cit., 116.

J " The Doctrine of Evolution in its application to Pathology," by
W. Aitken, M.D., F.R.S., in " Glasgow Medical Journal" for 1886.

Removal of Waste Products.

35

medical officers alike in India, in Egypt, and in the
Soudan, have of late been convinced of its occasional
spontaneous origin, as physicians in civil life have been
not less convinced in this country. And we all know
that under certain circumstances it too is contagious.
Brieger obtained a small quantity of a poisonous base
that he calls " typhotoxin " from cultivations of the
typhoid bacillus, which yielded reactions different from
the bases he had previously isolated from putrefying
animal matter, and Dr. Dixon Mann has obtained
a somewhat similar alkaloid from an enteric fever
case.

Hence the existence of a typhoid, (as well as of a
typhus) morbid or pathological series of ailments must
be recognised — a series in which ordinary typhoid fever
stands between the simple fever of over-taxation and
orthodox typhus— and this vitiation of the system may
be from without or from within. Auto-infection may
start the epidemic or the inhalation of morbific organic
emanations, of either of which we as yet know nothing,
beyond the fact that whatever may be the source or
combination of the etiological factors, the concurrence
of their action is recognised in the stupor or ru(po;
which is so characteristic of the clinical aspect of the
patient, and which gives the name to this condition.

In connection with the formation and ehmination of
waste products, we may also notice (before leaving this
part of the subject) that even here throughout the body
there are most elaborate arrangements for removing
waste products. In the muscles the fascia which sur-
rounds them forms a pumping arrangement, because of
the two layers of which it consists being separated from
each other at each muscular relaxation and pressed

d2

86

The Animal Alkaloids,

together at each contraction.** The lymph and the
waste products which it contains are thus actually
pumped out of the muscles at ea-ch contraction and
sent onwards into the large lymph spaces and lymph
channels, so that muscular action of itseK alone re-
moves waste products. At the same time the move-
ments of the muscles of the arm and leg will also pump
out blood from the veins sending it from the hands and
feet and so pressing it onwards to the trunk. This
was a well-understood physiological phenomenon in the
days when bleeding from the arm was a usual practice
in the spring and fall of the year ; when the apprentice
of those days requested the patient to manipulate the
lancet case in his hand, or when he was made to twist
about the pole or staff when barbers did the then con-
ventional operation of blood-letting. The movements
of the muscles, thereby secured, caused the blood
to flow upwards through the veins, so that a full and
satisfactory outflow into the basinf was obtained.
The movements of the abdomen and thorax in the acts
of respiration secure a similar pumping arrangement,
by which any excess of serous fluid, which bathes the
intestines and lungs, is pumped out of the peritoneal
and pleural cavities by the action of respiration.
These movements also indirectly influence the removal
of waste products from the brain and spinal cord.
They are further aided by the stimulus of mental ac-
tivity, so that when the brain is over worked and the re-

* Ludwig's "Genersioh," p. 63, Ludwig's "Arbeiten," 1870, in
Brunton, loc- cit. pp. 250 and 332.

t The basin with its scooped out edge, and the pole or long staff
with its painted bandage now remains as the barber's sign, remind-
ing us that ho was tlie phlobotomist of days long gone by.

Symptoms of Animal Alkaloid Poisoning. 37

spiration and muscular movements are under worked
cerebral nutrition comes to be diminished by the imper-
fect removal of waste products from its substance. Its
cells and fibres may be still further poisoned by the
circulation within the vessels which supply them with
blood full of noxious substances due to imperfect
digestion and assimilation.

For all these conditions abstinence from food is the
best remedy, and especially abstinence from alcohohc
liquors. It is in the weU fed who have little exercise
ajid in whom inadequacy of the function of Uver,
kidney and other organs, generally prevail, that the
symptoms of lassitude and sinking after meals are
mostly seen, and which Dr. Lauder Brunton justly
regards as a condition of poisoning, " both on account
of the time of its occurrence during the absorption of
the digestive products, and by reason of the peculiar
symptoms, namely, of a sense of weight in the arms
and legs," as if they were lumps of lead. These are
symptoms which resemble the effect produced by a
poison hke " curare," the action of a paralyser or
depressant of motor nerves or centres. The recent
researches just referred to render it very probable that
peptones are the poisonous agents in these cases — a
conclusion confirmed by Dr. Lauder Brunton's obser-
vation that " the weakness and languor are apparently
less after meals consisting of farinaceous food only."

So much for the clinical phenomena associated with
the cumulative action of the unknown " extractives,'"
the result of physiological metabolism.

Let us now consider the phenomena in relation to
" animal alkaloid poisonin/j," that is to cases in which
hypothermia predominates.

38

The Animal Alkaloids.

In Germany the typical condition is known by the
name of " botulism," a form of poisoning which results
from the ingestion of putrefying meats.

Such ailments of flesh or meat origin are in reality
the products of dead animal matter. So long as the
meat is fresh it may be wholesome ; but if in process
of putrefaction it ceases to be so, both Selmi and
Gautier have shown that it is by reason of such putre-
fying meats containing cadaveric alkaloids — the " pto-
maines " — that it becomes deleterious. Further, when
a solution of peptone is treated with potash and ether,
it yields a body which appears to be a volatile alkaloid,
and if j)utrid peptone is treated in the same way a solid
non-volatile alkaloid is obtained.*

But "ptomaines " are not only found in dead bodies,
they are also found in the intestines by the decomposi-
tion of parts of its contents. They have been found in
large quantities by Bouchard, both in the stools of
persons suflfering from diarrhoea or typhoid fever, and
in normal faeces. They appeared to be absorbed by the
intestine into the blood, and excreted by the urine,
(see p. 54). Thus, they have been found by Bouchard
in the urine, both in health and disease, and Bocci has
shown that the human urine has a paralysing action on
frogs hke that of curare or of the " ]3tomames," which
Mosso and Guareschi have obtained from putrefied
fibrine or brain. f Some time ago Dr. L. Brunton
pointed out the resemblance between the languor and
weakness which occur in many cases of indigestion,
and the symptoms of poisoning by curare, and drew

* Tanret, "Comptes Rendus," scii., 1163, quoted by Brunton, he.
cit., p. 351.
t Dr. L. Brunton, loc. cit., p. 351.

Absorption of Ptomaines.

39

attention to the probability that the languor was due to
the effect of poisonous substances absorbed from the
intestine. These he considered to be probably pep-
tones, but they may be " ptomaines," and whichsoever
they may be, the function of the liver is of importance
in preventing them from reaching the circulation. This
large gland prevents the passage of injurious substances
from the intestinal canal into the blood.'"'

Thus, the albuminoids seem to undergo the same
changes in the intestine as they do in artificial putre-
faction brought about outside the body, so that if the
chyme is retained overlong in the small intestine, the
aromatic j)rodacts of albuminoid putrefaction will
gather in excessive quantity ; and these various aro-
matic products of the putrefaction of albumen are
equally well obtained, whether it is set up by the
addition of sewer-mud or of pancreas ferment. f The
same series of changes may also be set up in putrid
pleurisy, stagnating secretions of the bronchi, in pul-
monary gangrene, and in balanitis. (Brieger), Thus
also the system generally may come to suffer by ab-
sorption into the blood of such soluble products of
decomposition as the " ptomaines " may supply, un-
organised chemical substances poisoning the system.
But, as it has been shown that the liver has a most
important function, namely, that (amongst others) of
destroying the poisonous properties of peptones and
perhaps of " ptomaines," and other substances pro-
duced during digestion, and possibly also of the poisonous

* "Indigestion as a Cause of Nervous Depression," Practitioner,
vol. XXV , Oct. and Nov., 1880.

t " General Pathological Anatomy," Ziegler, translated by Dr. D-
MacAlister, vol. i., p. 276—281.

40

The Animal Alkaloids.

products of waste tissue, any combination of factors
■which interferes for any length of time with such
normal functions as are exercised by this (the largest
gland in the body) may prove rapidly fatal, or at any
rate induce very serious ailments.

Tracing the origin of an epidemic of purging and
vomiting among soldiers in the Punjaub, Surgeon Frith
obtained from some suspected milk a crystalline sub-
stance of unpleasant odour and taste, which com-
municated similar symptoms to men and dogs. Pure
milk after standing for two months yielded the same
substance. So also C. Gram obtained from lactates of
the bases of the ptomaines — from putrid meats when
exposed to heat — poisonous results. These facts seem
to illustrate the ready formation of poisonous ptomaines
fi-om milk.** " From partial decay cheese similarly
sometimes acquu'es irritant properties, and will give
rise to vomiting and purging, more or less violent, in
those who have eaten of it. Pickled or tinned salmon,
salted herrings, and even fresh mussels, are examples
of articles of diet which have caused poisonous sym-
ptoms in those who have partaken of them. In 1856
Panum (the eminent professor of physiology at Copen-
hagen) showed that these effects were the result of
some chemical poison (an animal alkaloid) developed
in putrefying material. He subjected the fluid to
prolonged boihng so as to destroy any living organisms,
and on injecting it into animals the poisonous effects
were still produced, though in a shghter form than
from the unboiled fluid. Further, after filtering the
fluid and boiling it for an hour, he evaporated it to
dryness, then digested it with absolute alcohol, and
* Tbc "Lancet," 18S7, vol. i., p. 213.

Poisoning from Intestinal Products.

41

treated the residue with boiling water. This watery
extract also was poisonous."**

In looking therefore at the clinical evidence and
symptoms of the action of the ptomaines and leuco-
maiues, we must recognise in them the results of
"Indigestion as a cause of nervous depression. f Sleep-
lessness, drowsiness, and languor, are the symptoms
which are associated with such indigestion. It would
therefore seem " that the vital processes are more
readily arrested by the accumulation of waste products
within the organs of the body, than by any want of
nutriment to the organs themselves. We are now also
completely ahve to the important results produced by
the absorption from the intestinal canal of poisonous
matters introduced from without ; but we are not yet
sufficiently ahve to the important results produced from
absorption by the intestinal canal of substances gene-
rated in it by fermentation or imperfect digestion. We
recognise the danger of breathing gas from a sewer, but
probably we do not sufficiently realise that noxious
gases may be produced in the intestine ; and, being
absorbed from it into the circulation, may produce
symptoms of poisoning. And yet we know from re-
corded observation that such is the case, and that one
at least of the chief components of sewer gas, namely,
sulphuretted hydrogen, may be produced in the in-
testine. This gas, which is so readily recognised by its
smell resembhng rotten eggs, was found by DumarquayJ
to be very quickly absorbed indeed from the intestine
when injected into the rectum, and to be quickly ex-

* Dr. Latham's "Harveian Orations," 1888, p. 18.

t Dr. L. Brunton in " Practitioner," vol. xx., Oct. and Nov., 1880.

X "Comptes Rendue," ix., p. 724.

42

T}ie Animal Alkaloids.

creted from the lungs, sometimes appearing to produce,
during its elimination, an inflammation of tlie trachea
and bronchi. This was especially the case when small
quantities were injected, and it seems not improbable
that the production of this gas in the intestines may
have sometliing to do with the bronchitis which is not
unfrequently observed in connection with digestive dis-
turbances. In cases of indigestion this gas seems to be
not unfrequently formed, because persons often com-
plain of the taste of rotten eggs in the mouth or in the
eructations. Even in small quantities it is not im-
probable that it may exert a deleterious influence both
upon the nervous system and upon the blood ; for it is
a powerful protoj)lasmic poison, somewhat resembling
hydrocyanic acid in its action."*'* Butyric acid which
is also formed in the stomach in some cases of in-
digestion, has been shown by 0. Weber to be a powerful
poison, acting chiefly on the nervous system.

" It seems probable, however," as Dr. Brunton ob-
serves, " that the substances, both gaseous and sohd,
formed in the stomach and absorbed from it, are upon
the whole less poisonous in cases of indigestion than
those which are produced lower down in the intestinal
canal. We often find that patients are affected with
severe gastric disorder without any affection of the
nerve-centres, beyond the weakness produced by the
inability to digest food ; while in many persons the
mere omission to evacuate the contents of the bowels
at the usual time will lead to a headache in the course

of the day which it is quite possible may be due

to the absorption of some of the elements of the fjecal
matter itself." Nor do we know at present what may

• Dr. T. Lauder Brunton, "Disorders of Digestion," p. 240.

Action of Liver on Digestive Ferments. 43

be the effects of the absorption of the various digestive
juices themselves and the ferments they contain, of the
bile, of the gastric juice and pepsine, of the pancreatic
juice and jDancreatine, and of the " succus entericus."
That absorption of these juices takes ]3lace there can be
little doubt. It has been demonstrated with regard to
the bile that it is absorbed with great rapidity from the
intestine, and re-excreted by the hver, so that it may
not pass into the general circulation at all. Pepsine
qn the other hand finds its way in minute quantities
through the liver, and has been discovered in various
tissues of the body and in the urine. So also with the
pancreatic fluid ; but with regard to mere absorbed
digestive fluids, Dr. Lauder Brunton has pointed out
that " it seems not unlikely that the liver has got
another function (besides those usually assigned to it)
namely, that of preventing the digestive ferments from
reaching the general circulation so as to act upon the
tissues." If therefore this function should ever be in
abeyance, then we may expect to have deleterious re-
sults. There is no doubt also that the products of
intestinal digestion undergo very remarkable changes
in the hver, as shown by the formation fi-om them of
very large quantities of " glycogen," a substance which
does not exist in the products of the gastric and in-
testinal digestion which reach the liver. Under ordi-
nary circumstances in health, nearly the whole of the
sugar formed in the intestine and absorbed from it, is
arrested in the hver, so that very Uttle ought to pass
into the general curculation to be excreted by the
kidneys.

But albummous substances, the products of intestinal
digestion, and peptones also, occasionally make their

44

The Animal Alkaloids.

appearance in the urine, and the products of nitro-
genous waste frequently occur in the form of lithates in
the urine, any excess of which indicates some patho-
logical condition, however trivial it may seem to be.
These may also appear in the urine after excessive
or violent muscular exertion, accompanied by profuse
sweating, so that they may possibly represent some of
the products of muscular waste. On the other hand
they also may occur in the urine in large quantities
after slight indiscretions in diet, although no muscular
exertion has been gone through. They can then only
represent the products of the imperfect assimilation of
nitrogenous matters which ought to have been eh-
minated not in the form of urates but of urea. But as
physiological experiment and observation indicate that
the Hver is the chief, if not the only part, of the body
in the healthy state in which urea is formed, the old
notion which connects the appearance of hthates in the
urine with disordered function of the liver, is probably
in a great measure a correct notion still. Then* pre-
sence indicates defective assimilation, so that they may
be accompanied by the formation of other substances
which have a much more pernicious action. " Hence,
the importance of the functions of the liver in reference
to assimilation is now generally recognised ; although
for a long time this, the largest gland in the body, was
considered to have no other function than simply to
secrete bUe." The greatest care appears to have been
taken in the construction of the liver to prevent the
bile coming in contact with the blood, or entering the
general circulation ; and the effect of bile acids circu-
lating in the blood (as shown by physiological ex-
periments) is to depress the functions of the spinal

Injurious Properties of Beef-tea.

45

cord, to impair and lessen the functions of the brain,
producing drowsiness, ending in coma ; and to weaken
the cu-culation by paralysing the cardiac ganglia.**

Dr. Lauder Brunton has further shown that certain
albuminous products of intestinal digestion and pep-
tones occasionally make their appearance in the urine.
Amongst the former is an albuminous substance not
precipitated by boiling, but by nitric acid in the cold.
This substance Dr, Brunton observed in the urine of a
healthy man after he had drunk a large quantity of
strong beef-tea at a draught on an empty stomach ;
and in examining the beef- tea a similar albuminous
substance was found in it. In this case the albumen
seemed to be so rapidly absorbed from the stomach or
intestines, that it passed without change through the
portal system into the general circulation, and thus
reached the kidneys where it was excreted in much the
same way as sugar would have been under similar
circumstances. f Under certain conditions therefore,
of impau-ed functions of the Uver especially, beef-tea
and such Uke products may be actually injurious, so
that the products of muscular waste (which really con-
stitute the chief portion of beef-tea or beef-essence),
may under certain circumstances be actually poisonous,
and to this poisonous property the stimulant action of
beef-tea may be due in the first instance, and its
administration, like that of alcohol, may in some cases
be overdone, and the patient weakened instead of
strengthened. "In many cases of nervous depression
we find a feeling of weakness and prostration coming

* Wickham Legg, " Bile, Jaundice, and Bilious Diseases," p. 207-
216, 217.

t Dr. Lauder Brunton, •'Disorders of Digestion," p. 247.

46

The Animal Alkaloids.

on during digestion, and becoming so very marked
about the second hour after a meal, and at the very
time when its absorption is going on, that we can
hardly do otherwise than ascribe it to actual poisoning
by digestive products absorbed into the circulation."
And from observation of a number of cases. Dr. Brunton
came to the conclusion that the languor and faintness
of which many patients complained, and which oc-
curred about eleven and four o'clock, was due to the
actual poisoning by the products of digestion of break-
fast and lunch.

Since these observations of Dr. Brunton, experimental
data have shown that the products of digestion were
actually poisonous in themselves, so that Dr. Brunton's
conclusions from chnical observation have been con-
firmed by experiments made in the physiological and
pathological laboratories of Albertoni, of Genoa, and by
Dr. Schmidt- Miihlheim, in Professor Ludwig's labora-
tory at Leipsic. By these observers it has been shown
that peptones have the power of completely destroying
the coagulability of the blood in dogs ; and but httle
power in this respect over the blood of rabbits and
sheep ; and so far as experiments go, it would seem
that peptones prevent the coagulability of the blood in
carnivora and not in herbivora. Under Professor
Ludwig's direction of experiments it has been found
that when peptones are injected into the chculation by
a vein, they greatly depress the circulation, so that the
blood pressure falls very considerably ; and when the
quantity injected is large they produce a condition of
sleepiness, complete arrest of the secretion by the
kidneys, convulsions and death.
From these experiments it is evident that the normal

Poisons from Food-Decomposition.

47

products of digestion may become poisons of no incon-
siderable power ; and that if, through inadequacy of
organic functions they reach the general circulation in
large quantities, they may produce very alarming, if
not dangerous, symptoms.

Practically the nature of peptones has still to be
investigated. It has been usual to consider them all
as one and the same, out of whatever digestive ferment
they may have come. But it is quite possible that the
peptones differ as much from each other as different
kinds of sugar differ.*'' Usually they disappear from
the blood before it reaches the general circulation, and
even in the portal blood before it reaches the liver, very
little, if any, peptone is found ; but it is not yet known
where peptones undergo changes. Some regard the
liver as the seat of their transformation, which may
to some extent prevent any peptones from getting into
the general circulation, which may have escaped trans-
formation in the portal blood before reaching it
(Brunton, Schmidt-Miihlheim, Albertoni).

Another phase of the clinical evidence and symptoms
of the action of the ptomaines and leucomaines must
be recognised in " the poisons formed from food, and
their relation to biliousness and diarrhoea. "f

The poisonous alkaloids formed from various sorts of
proteid elements in food decomposition, produce sym-
ptoms and sensation of discomfort which are referable
partly to the digestion and partly to the nervous system,
and at periods varying from a few hours after the food
which disagrees, or after it has been in use and con-

• Dr. Lauder Brunton, Zoc. cit, p. 24S.

t Dr. Lauder Brunton, "The Practitioner," vol. xixv., August,
September, October, 1885, also "Disorders of Digestion," p. 275.

48

The Animal Alkaloids.

tinued for several days. Eggs and milk when so con-
tinued in a monotony of diet, are thus apt with some
to cause an unpleasant taste in the mouth, general
discomfort and frontal headache ; or after persevering
in such diet for some two or three days, the appetite
becomes impaired, the intellect becomes less clear, the
conjunctivaB shghtly yellow, headache sets in, and the
discomfort may culminate in an attack of vomiting or
diarrhoea — preceded or not by constipation, on account
of which eggs and milk are popularly believed to be
"binding" as to the function of defaecation. But
although we do not yet know the bearing of these well
known observations and popular behefs on the patho-
logy of disease. Dr. Lauder Brunton has shown that
" the cardinal fact which results from all these re-
searches is that the " proteid substances," such as
albumen, fibrine and gelatine, which are themselves
foods, become spht up so as to yield the poisonous
"ptomaines " or " leucomuines," and that such poisonous
products may be brought about by the digestive fer-
ments of the healthy body, or by the metabohsm which
goes on during the normal physiological processes of
life. It also appears that these self-generated poisons
vary not only according to the particular body which
is decomposed, but to the particular ferment which sets
up decomposition, to the temperature at which it occurs,
and to the length of time it continues. The process
may also be much modified by other factors, such as the
quantity of moisture in the albuminous substance itself,
or in the atmosphere generally ; also by electrical at-
mospheric conditions, such as those which occur dur-
ing or after a thunderstorm, when meat as well as
milk often becomes "tainted" during the electrical

Mxiscarine and Atropine-lilce Poisoning.

conditions, when "thunder" is said to be "in»1the
air."*

Vomiting and purging are among the most charac-
teristic symptoms of poisoning by the putrefactive
alkaloids; but the most marked symptoms which the
poisonous ptomaines and leucomaines produce (such as
neurine, muscarine and choline) are salivation, diar-
rhoea and vomiting, dyspnoea, paralysis and death.
They seem to stimulate the secretion of glandular
organs, for along with salivation there comes a flow of
tears, and the secretion of the bronchial mucus becomes
more abundant and fluid as shown by the occurrence of
moist rales within the chest. They also render the
heart's beats slow and weak; and one of the most
marked characteristics in the action of these poisons,
is the effect of " atropine " as an antidote to them.
Dr. Lauder Brunton regards paleness of the face as a
symptom which indicates the presence of a muscarine-
hke poison — in addition to one like atropine, in which
the skin is scarlet — the muscarine-like poison predomin-
ating. The existence of a muscarine-like poison is still
further indicated by the presence of diarrhoea, alternat-
ing with constipation and colic ; the pulse slow, small
and almost imperceptible — a condition which Brunton
considers typical of muscarine poisoning ; while in atro-
pine poisoning " the pulse is rapid from the complete
paralysis of the inhibitory fibres in the vagus, which
the poison produces. f "It is possible" therefore "that
instead of there being two or more poisons having a
partly antagonistic action, there may be only one
having an action resembling atropine in some respects

* Dr. Laudor Brunton, loc. cit , p. 279.
t Loc. cit., p. 28G.

E

50

The Animal Alkaloids.

and muscarine in others. In some cases of poisoning
by fish, the symptoms have resembled those of poison-
ing by atropine ; namely, dryness of the mouth, difficulty
of swallowing, weight of the limbs, paralysis of the
superior and inferior recti and of the oblique muscles of
the eyes, as well as ptosis and paralysis of accommoda-
tion, dilatation of the pupil and double vision ; but the
pulse not quickened as in poisoning by pure atro-
pine. The alkaloid obtained by V. Anrep from poison-
ous fish produces similar symptoms to those caused by
the fish itself ; and in like manner the alkaloid obtained
from poisonous cheese (tyrotoxican) produces symptoms
similar to those caused by the cheese. If these alka-
loids were obtainable in a state of perfect purity we
should be obliged to regard them as having an action
similar to atropine in many respects, but differing from
it in respect to their action on the pulse. But there
are many vegetable alkaloids hitherto supposed to be
pure, which have been shown recently to be mixed with
others having a perfectly opj)osite action ; hence we
may regard it as propable that the symptoms of poison-
ing by sausages, fish,*' cheese, and the like may be due
to a mixture of the alkaloids. |

* Mackerel Poisoning. — To the Editors of the Lancet.

Sirs.— Referring to your note on mackerel poisoning, it may
possibly interest some of your readers to know that fishermen have
a saying that white mackerel is the best, then green, but that the
red variety is poisonous. In Guadaloupe there is a red boned
mackerel used as a rat poison. There are known and noted already
upwards of seventy different kinds of food fishes, which within a few
hours after their death are reported to undergo such decomposition
in their bodies or flesh as to give rise to poisonous symptoms after
being eaten by man. So convinced is the Russian Government of
the importance of this question that it offers in 18U4 a prize of 5000

Pathology of Fish Poisoniiuj. 51

In cases of poisoning by the ptomaines having a
purely atropine-Uke action, the adminiHtration of phy-
sostigma either by apphcation to the eye, or by subcu-
taneous injection is that which is indicated and which
has been adopted in one case at least (Brunton).

The presence of choline, neurine, or muscarine, may
be made manifest by the production of diarrhoea, alter-
nating with constipation, in the presence of an antago-
nistic atropine-like poison. If, however, they are
present alone, or singly, the symptoms most likely to be
produced are salivation, vomiting, purging and collapse,
according to the amount of the poison.

Atropine as a remedy has been found to do good in
a case of muscarine-like poisoning from unwholesome
food (Brunton).

Of the alkaloids isolated by Brieger from human
cadavers in certain stages of decomposition two of them
have been proven to possess a powerful physiological
action. One of these when injected into the veins of
guinea-pigs, or rabbits, appeared to aflfect the intestine
alone ; and to have no action on any of the other
organs. It caused an enormous increase in the peri-
roubles (say, £500) for the best essay on the nature and cure of fish
poisoning. None of the fish found in the Norwegian waters are
poisonous. It has been stated that all living- healthy fish swarm
with bacteria in their blood and lymph, which bears out my own
observations regarding the early and rapid rate of decomposition of
even freshly caught fish. Hence I have long advocated that fish on
capture should be immediately bled and gutted. The bleeding must,
of course, take place before clotting; but British fishermen and
fishmongers only gut their fish after clotting has taken place.
I am, Sirs, your obedient servant,

J. Lawrence-Hamilton, M.E.C.S.

Folkestone, June 8th, 1889.

t Dr. Lauder Brunton, loc. cit., p. 287.

e2

52

The Animal Alkalvicls.

Btaltic action of the bowels, wliicli lasted for several
days and the continuous diarrhoea led to extreme weak-
ness of the animals. The other alkaloid, which Brieger
has named " mydalein," has a still more marked ])hy-
siological action of much clinical interest, inasmuch as
we find hyperthermia is amongst its symptoms. Its
physiological action is specific. When a very minute
quantity is injected into guinea-pigs or rabbits, saliva-
tion sets in, nasal secretion is increased, and a copious
flow of tears occurs. The pupils become dilated, the
vessels of the ear much injected, and the rectal tem-
perature rises from 1° to 2" per cent. The pupils
gradually dilate to the maximum and cease to react to
light The coat of the animal becomes staring ; and
sometimes they tremble. Gradually the sahvation
diminishes, the respiration and pulse become slower,
temperature falls and the animal recovers. Larger
doses to the extent of Jg- of a grain (under half a centi-
gramme)— are always fatal, and their action exceeding-
ly violent.

Many, but not all of these symptoms occur in men in
\ consequence of poisoning from decomposing food, or
from disease ; and it is possible that the occurrence of
some symptoms and not of others may be due to the
occurrence in disease of alkaloids allied to mydalein,
although not identical with it, or to the presence of two
or more alkaloids which partially neutrahse each other's
effects.**

Although, however, positive evidence may be as yet
wanting as to the formation of alkaloids within the
body ; it is highly probable that a formation of alka-
loids, such as has been described, does occur in the
» Dr. Lauder Bruuton, loc. cit, p. 289.

Self-intoxication in Disease.

63

intestine, because it has been found that such alkaloids
are formed in the freshly voided fa3ces. On this point we
have further clinical evidence furnished by Dr. Lauder
Brunton. " No one " he writes, " who has watched
cases of acute disease, such as pneumonia, can have
failed to see how a rise of temperature sometimes coin-
cides with the occurrence of constipation, and is
removed by opening the bowels. In the case of such
an acute disease as pneumonia, one has hitherto been
unable to say definitely why constipation should pro-
duce this rise of temperature, but it seems not impro-
bable that it may be due to the absorption from the
intestine of some ptomaines (or to the retention of some
of the unknown extractives which ought to have been
eliminated). In his work on " Purgative Medicines"
also, Hamilton says that " in cases of typhus fever the
administration of an antimonial remedy was beneficial
only when it moved the belly. In this case the fseces
were black and foetid, and generally copious. On the
discharge of these, the low delirium, tremor, floccitatio,
and subsultus tendinum which had prevailed were
abated ; the tongue which had been dry and furred,
became moist and cleaner ; and a feeble creeping pulse
acquired a firmer beat."
Bouchard has still further shown in his lectures on
Self-intoxication in Disease " that the poisonous
activity of human fteces is very great even when they are
quite healthy (see p. 10, ante). Since the first edition of
this book was published. Sir Andrew Clark read a paper
before the Medical Society of London, Nov. 14th, 1887,
on " Chlorotic Anaemia " in which I am pleased to see
that so distinguised an authority adopts and confirms
the conclusions of Bouchard. In that paper ho says

64

The Animal Alkaloids.

that it is »' impossible to doubt that poisonous alkaloids
are formed in the ahmeutary canal ; that when excre-
tion is seriously diminished, they must be in some
degree absorbed ; and that mixing with the blood, and
entering the tissues, they must produce some sort of
injurious effects determined by the rate of absorption
and the amount absorbed."*

He further goes on to show that the treatment which
most speedily and effectually cures chlorotic anaemia, is
a treatment which by the use of tonic aperients produces
full and regularly recurring action of the bowels. With
the suspension of this treatment the disease recurs ;
with its resumption the disease again subsides, and no
treatment appears to be permanently successful which
does not provide means for seciu-ing daily rehef to the
intestinal canal. He then gives details of this treat-
ment,-j- and records as the result of his extensive ex-
perience that were he limited to the employment of one
sort of drug in the treatment of chlorotic anaemia, the
di'ug he should choose for use would be an aperient.

That alkaloids are present in the circulating blood, is
shown by the fact that they are separated from it by
the kidneys, and are found in the urine ; and according
to Lepine and Guerin the poisons contained in the
urine in different diseases differ in their physiological
action. The extract obtained from the urine in cases
of typhoid fever produced in frogs increased reflex
action and death after three hours, the heart being
usually found in a state of diastole. In cases of pneu-
monia the urine had a similar action, except that the

• "Lancet," Nov. 19th, 18>7, p. 1005, also "Med. Soc. Pro-
ceedings," vol. xi., p. 55.
t hoc. cit., " Lancet," p. 1005, and " Proceedings," p. 63.

Ptomaines formed in Disease.

55

heart was found in a more or less contracted state,
varying with the severity of the case from which the
m'ine and its poison had been obtained.

It has been stated that thrombosis in the puerperium
takes place independently of septic influence. But it
has been abundantly shown that the constitutional
condition of the female after delivery is an exceptional
one physiologically ; and that there are sources of
septic matter which arise in the patient's own system,
from repressed secretion and other causes. An
enormous quantity of effete matter is thrown into the
circulation during the involution of the womb, and if
this is not rapidly discharged, urtemia and fever result.
Thus, thrombosis, as well as broncho-pneumonia, may
set in. The puerperal blood highly charged with
fibrine, and a noxious stuff capable of producing coagu-
lation in the living vessels, are the factors necessary
for the production of thrombosis.

Arrest of secretion thus plays a most important part
in the induction of puerperal fever, so that metero-
logical influences and conditions should in future be
registered, together with the usual factors in the eMnical
records of puerperal diseases.**

Hence there appears to be Httle doubt that the
amount of ptomaines formed in the body in disease is
greater than it is in health ; and very probably they
are of a different character, possibly varying with the
disease, f Their existence in disease can only be
proved by searching in the cadaver for them, and by

• Dr. Robert Barnes in Meeting of Obstetrical Society, "Lancet," "
May I8th, 1889. See also "Science and Practice of Medicine," vol.
i., p. 315, 7th edition, by William Aitkun, M.D., F.R.S., 1880.

t JDr. Lauder Brunton, he. cit., p. 290.

56

The Animal Alkaloids.

the chemical examination of the excretions during life.
"Although it may be admitted that the chances are
against the isolation of a ptomaine formed during life
{i.e., a morbid leucomaine) and which has been the
cause of death,** still until the attempt has been re-
peatedly made, the question can by no means be
regarded as conclusively settled. Improved methods
of investigation may accomplish what at present seems
impossible."

Dr. Dixon Mann has for some time past investigated
this part of the subject practically in the Toxicological
Laboratory of Owens College ; and has placed on
record the results he obtained in a case of enteric fever,
in which death occurred suddenly from perforation of
the bowels during the third week of the fever. Follow-
ing the process devised by Brieger, and which so far as
his experience goes, yields the best results. Dr. Dixon
Mann obtained fine needle-shaped and highly deK-
quescent crystals, whose forms and reactions estabhshed
the identity of the body with choline — a j)tomaine
common to all cadavers, and the first that appears
in the usual sequence of post-mortem changes. So
far he obtained no specific result. But he still
further examined the residue to see if any ptomaine of
a special character, in relation to enteric fever, was
present in it. He then obtained a quantity of fine
colourless needle-shaped crystals, which gave certain
reactions, which he describes, and which differed fi'om
those obtained by Brieger, with the substance he named
" typhotoxin." Dr. Mann further experimented with a
solution of needle-shaped crystals in water, by injecting
a few drops under the skin of a guinea pig. The chief
* Dr. J. Dixon Mann, "Medical Chronicle," March, 18S8.

Pathology of Acetonemia.

57

toxic effects of this ptomaine were motor paralysis and
general insensibility, both of which supervened very
rapidly. Examination after death showed the heart in
dyastole, the bladder empty and contracted, and the
bowels containing some mucus similar to that which
was discharged after the reception of the ptomaine.
In a second case of the same disease the result was
negative. (See also Luff in " Brit. Med. Jour.," July,
1889, p. 193).

Most of the alkaloids which have been obtained by
the decomposition of albumen appear to belong to the
leucomaines of the " muscarine " type ; and to have a
tendency to cause diarrhcea ; but some appear to
belong to the " atropine " type, which to a certain
extent counteracts the effects due to "muscarine."

In the peculiar condition called " Kussmaul's coma,"
or " diabetic coma," we have another example of the
self-infection of the system, or autochthonous evolution
of disease by the formation of poisonous compounds
within the body. It is an evolution, however, which is
shown to be not peculiar to diabetes, but occurs in per-
nicious anaemia and in the typhoid states, presumably
through some (as yet unknown) chemical decomposition
occurring within the body, and affecting the blood or
other fluids. It has been described under the name
of " acet07i(Bmia," in the belief that it is due to ^'acetone"
in the blood. The condition certainly betokens a sud-
denly spontaneous self-infection process and usually
a rapid death. The blood is pale and cream-Hke, or
hke grumous pus. It does not clot, but on exposure
to the air it becomes pink and brighter in colour — of a
magenta-Hke tinge. The microscope shows the creamy
condition to be due, not to fat, but to the presence of

58

The Animal Alkaloids.

a large quantity of molecular matter, -which does not
dissolve in ether. The action of acetone on healthy
blood is found to be similar.*'* The blood corpuscles
break down into granular debris ; and such destructive
effects of acetone on the blood accounts for such sym-
ptoms as great dyspnoea and cyanosis ; for the blood
cells are so destroyed that tbey are no longer able to
absorb and fix oxygen. In 1857 Fetters and Kaulich
showed that acetone was developed in the blood of
diabetics, as well as in chronic afi^ections of the
stomach and digestive organs, such as chronic gastric
catarrh. The state of acetonsemia of various forms
brings about great de^jression of the whole nervous
system ; and the source of the acetone is probably from
the alcoholic and acetous fermentation of the grape
sugar, and possibly of other organic matters in the
stomach in catarrhal conditions, f Acetone has also
been found in the blood and in the solid organs of
patients dead of diabetic coma.| It has been
found in the urine ; and is often developed in the urine
after it has been passed. § Von Jaksch Penzoldt, and
others, have shown that acetonuria is not pecuhar to
the diabetic condition but may occur in a variety of
febrile states ; and that there are grounds for beheving
that even the healthy organism may not be altogether
free from acetone. It would appear from the researches
of Baginsky, that amongst children a physiological
acetonuria of shght degree and inconstant nature, does
exist ; that a pathological acetonuria is common

* "British Medical Journal" for 1878, p. 79, Foster and Saundby.

t Beohamp, "Compt. Rendus," 1872.

Z Berti, " London Medical Record," 1874.

§ Foster, Zoo. cit., and Kussmaul.

Typical Symptoms hi Ptomaine Poisoning. 59

among children suffering from febrile disorders ; and
further, that the presence of acetone in the urine
appears to be related directly to the intensity of the
febrile process. But, as yet, we neither know for
certain the place at which acetone originates, the
materials out of which it is constructed, the precise
effects on different tissues, nor its ultimate fate in the
metabolism of the tissues. It appears probable, how-
ever, that nitrogenous disintegrations may be the source
of this chemical body.**

In such blood poisoning there is great muscular
feebleness ; the pulse is quickened ; and deep slow
breathing is induced like that of alcoholic poisoning,
followed by coma and antesthesia. Suddenly the
clironic poisoning takes on an acute form like delirium
tremens,^ when death speedily ensues.

In view of the extraordinary activity of some of these
alkaloids — the ptomaines and leucomaines— we cannot
wonder at the violent symptoms which sometimes occur
after the use of tainted meat, nor even at the extra-
ordinary poisonous action of eggs in some persons ;
and it is probable that the diarrhoea and vomiting
which are characteristic symptoms of such poisoning
may be due to the decomposition of the proteid ele-
ments of such kinds of food in the intestinal canal
itself.

Thus it comes to pass that a typically morbid or
pathological series of phenomena have been seen to
follow the ingestion of various " animal alkaloids ; "
characterised especially by choleraic diarrhoea, vomit-

* "Lancet," vol. ii., 1885, p. 392, and vol. ii., 1887, p. 492.
t Ziemsaen'a "Cyclopaedia of Practical Medicine," vol. xvi., Art.
" Diabetes."

60

The Animal Alkaloids.

ing, cramps, algidity and the like, presumably induced
by the "ptomaines " whicli have been elaborated from
the articles of animal diet in progressive stages of
decomposition. Hypothermia predominates in such
cases, precisely such as may be observed in poisoning
by tartar-emetic or arsenic. In cholera similar pheno-
mena are characteristic, diminished temperature and
algidity accompany the digestive troubles.

May we not therefore recognise in these affections
the evidence of poisoning by a toxic alkaloid, or alka-
loid of purifaction ; and that certain nutritive ingesta
may give rise to the formation of such toxic alkaloids ?
" Hence it is no great stretch of scientific hcense for
us to recognise or trace in pathology a very natural
series of morbid phenomena or ailments starting from
the ' botulism ' of the Germans up to Asiatic Cholera."**

We are also justified in holding that there are in
pathology a morbid series of ailments as legitimate as
those natural series of things with which we are fami-
Uar in Chemistry, Geology, Palaeontology, or Botany.
Variation and gradation are the rule in Nature, alike in
Pathology, as in other departments of Natural Science ;
and in recognising the fact that the "animal alkaloids"
can be elaborated by the spontaneous physiological
processes of life, I am once more brought to the conclu-
sion I attempted to expound four years ago, namely : —
that in facts such as I have detailed in these pages we
have additional evidence that " The Doctrine of Evolu-
tion is capable of explaining the origin of some dis-
eases."!

We must also ever keep in view the circumstance

* Dr. A. M. Brown, he. cit.

t " Glasgow Medical Journal," 1885-1886.

" Humoralism " in Pathology.

fil

that diseases are not " entities," but morbid processes
wliich are more or less slowly developed in the course
of physiological life ; and to study them with success
we must take that broad view of Pathology which fully
recognises in its investigations " the never old, and the
ever new." " It is not the fact that the human body is
ever taken possession of by some seed-Uke principle,
destined in the future infallibly to evolve the phe-
nomena which receive certain names. Eather by these
names we recognise the fully developed results of a
complex chain of causes. The order of events which
has in any given case ended in the production of such a
malady, was one which might have failed at any point,
or might have been broken by art. The right study of
rare diseases will induce us to forego the search for
entities, to disuse such terms as " siii generis," and find
pleasure in the discovery of laws of relationship rather
than divergence."''*

But really there is nothing new under the sun. In
this field of recent research which I have tried to open
up to view in the preceding pages, and which I may
have rashly described as new territory, I have only
turned over a new leaf and opened up a new chapter
in the Humoral Pathology of ancient days. In so
doing we once more bring to the aid of the Medicine of
the present day the Pathology of the past, as has been
so often done before. f Humoralism we know is of very
ancient date— old as the Grand Old Man of Cos ; but it
is still a fundamental principle in our healing art, which
we are sometimes not only apt to forget, but to ignore.

* Jonathan Hutohinaon, " Clinical Uses of Rare Diseases,"
"Lancet," May 18tli, lS89, p. 974.

t Aitken, " Soionco and Practice of Medicine," 7tb edit., vol. i.
p. 40.

62

The Animal Alkaloids.

lu the view I have endeavoured to expound as to
the antecedent factors which may combine to produce
disease we cannot fail to recognise a partial return to
Humoralism, seeing that poisoning or auto-infection
by soluble animal alkaloids is in reahty poisoning by
an organic liquid which has undergone deterioration ;**
and that from the chemical demonstrations of Gautier,
the clinical observations of Peter, and the critical ex-
positions of Drs. A. M. Brown and Lauder Brunton,
Dixon Mann, and others, the doctrine of spontaneity is
as true of health as of disease. Thus it is that our old
traditional records of Medicine still continue to hght
up our path by brilliant gleams of truth. Many factors
in the causation of diseases, and as influencing their
course, have now to be reckoned with, which before
were unknown ; and even if they were known to exist,
they were but little regarded ; and now looking to the
future we know not in what direction the next advance
in practical and scientific pathology may be made.

Prior to the time of Haller, our masters in medical
science, from mere observation, evolved a "Humoral "
Pathology, which to them explained not only the cause
of diseases, but also the cure of them, or the resulting
death of the body.

In due course of time (great improvements having
taken place in instruments of precision) clinical ex-
aminations came to be made more carefully and with
greater accuracy. Hence the comparison of such care-
fully made clinical records gave rise eventually to those
experimental methods which have so largely contributed
to our knowledge of pathology, especially by continental
pathologists ; while legislation in this country has been

* Dr. A. M. Brown, loc. cit.

Patholoijij of Infective Diseases.

68

not less influential in hindering the progress of experi-
mental pathology, and therehy obstructing the advance
of medical science. Under these influences the cellular
doctrines of Virchow came to be developed. The phy-
siology of cell-growth by Schleiden and Schwan led up
to this, and many a word battle has been fought over
the ceU-theory of disease. Bigger microscopes, with
more powerful lenses, afterwards enabled John Hughes
Bennett, of Edinburgh, to appreciate the importance
of molecules, and a " molecular " pathology swept, for
a time, the cellular pathology out of the field. The
explanations of the processes of disease based on these
theories appeared for the time to be conclusive.

But subsequent investigations with still more powerful
lenses, fostered mainly by experiments on animals, and
by micro- chemical tests, have recently led to the study
of minute micro-organisms in the form of bacilli,
bacteria and spores, so that a " bacLUary " pathology at
present holds the field, almost to the exclusion of all
else. It recognises the causation of some diseases as of
the nature of a parasitical influence. Professor Koch, of
Berlin, is the leader of this new school, with Pasteur in
France, Lister, Watson-Cheyne, Woodhead, Ogston,
Crookshank, and many others in this country and
abroad.

These observers teach that many diseases are now
ranked as infective, through the agency of these micro-
organisms, which were not so considered formerly; and
also that each such disease has its etiological peculiarities
demanding a prophylaxis, so special to itself, that the
general prophylactic principles based on present know-
ledge as to the nature of infection, have come to require
many far-reaching and comprehensive inquiries to be

64

The Animal Alkaloids,

made in directions altogether new, before "we can arrive
at a definite solution of the many sanitary and patho-
logical problems involved.

The micro-organisms as causes of diseases seem to
be as numerous and varied as the sands on the sea- shore ;
while their pathological domain has become so far-
reaching in extent, that every form of infective disease
seems bound to acknowledge some one or other form
of microbe as the author of its being. But the only
difference between these parasitic existences and those
of former times (then beUeved to be equally potent)
is that they are more minute, and require higher
powers of the microscope to see them. This beUef has
given a great impetus to the improvement of optical
instruments. Consequently also we have become aware
of a greater number of minute and hitherto unperceived
forms of parasitic organisms, some of which are set
down as causes of certain forms of grave diseases.
Hence these " bacterial " affections are very widely
diffused. But, as yet, no one has succeeded in making
out the manner in which such microbes act, or the
causal relation which exists between them and disease.
" The mere presence of such ' microbes ' in the system
cannot be described as disease. Disease only begins
when, owing to the presence of ' the microbe,' changes
take place in the tissues of the organism which induce
disturbances in their functions ; and the detection of
' microbes ' in the diseased organism is but the first
step towards the discovery of the cause of the disease
and its mode of operation.* In other words the pre-
sence of a microbe can but suggest an inquiry into
these antecedent factors which have combined to bring

* Ziegler, loc. cit., pp. 1 aud 2.

Bacteria very widely di fused

65

about the disease or the morbid conditions favourable
to the development of the "microbe," There is a great
gap still to be filled up in the interval between the
concurrent factors in the physiology of life which bring
about disease, and the stamps which are left by diseases
as evidence of their having existed, whether these be of
a microbial character or in the cruder forms of weU-
known morbid anatomical changes. It may even He
beyond the powers of the anatomist to follow the pro-
cesses of morphological change or of molecular trans-
formations recognisable only by the chemist, to whom a
region lies exposed to his pecuhar means of research,
which is as yet unexplored.

Certain it is that molecular death precedes all evi-
dence of the existence of the bacterial microbes ; and
hence their diffusion is enormously wide. Matters on
which they grow and thrive are found everywhere ; and
therefore whenever dead organic substances are found,
either in solution or with a certain amount of water,
there also bacteria may be found. They are found in
all waters, whether flowing or stagnant, in all liquids
that can ferment or putrefy, and in all vegetable and
animal tissues that are suiiiciently moist. Organic
matters, moisture and warmth go to favour their multi-
phcation ; and we cannot avoid swallowing numbers of
them with our food, and inhaling them with our breath.
Bacterial invasion of the system may thus start from
the mucous membrane " tn special circumstances ; " and
it is " in these special circumstances " that we must re-
cognise the antecedent unknown factors which combine
to bring about the disease, and contribute to the condi-
tions favourable to the existence of bacteria. " They
are unable to settle in a perfectly healthy body ; they can

F

66

The Animal Alkaloids.

only develop when the physico-chemical constitution of
the tissues is morbidly altered so as to correspond with
their requirements."

On the one hand therefore the " microbes " must be
endowed with certain vital properties of a special kind ;
and on the other there must be a predisposition of the
system in a certain physico-chemical constitution of the
tissues, so that the micro-organisms may find within
the body, and in proper combinations, all the conditions
necessary for their growth and development.

It has also been determined by experiment that very
sHght chemical changes in the constitution of a tissue
are enough to determine whether a given " microbe "
can develop in it or not. A local lesion yielding the
poisonous products of tissue necrosis or of wounds is
one of the commonest and most obvious alterations, but
there are many other instances in which the antecedent
■factors are as yet beyond our ken, either from their
apparent slightness, or because they are not such as
our tests can yet discover. All that is necessary is that
the " microbe " should reach a spot that affords the
conditions for its development.

We are thus driven to the conclusion that at present
the evidence regarding " microbes " tends to show
that they are entirely post hoc in relation to the ante-
cedent factors of any particular disease.

Nevertheless it has been accepted as j)roven, that the
" virus" or " infecting stuff" of (at least) two infective
diseases is a micro-organism ; and that in cases in
which this has not yet been accepted as absolutely
proven, the rise and progress of them are so similar to
those in which micro-organisms have been shown to be
the virus, it is assumed that all the infectious diseases

Experiments regarding Anthrax. G7

are entitled to rank amongsl these parasitic affec-
tions.

But accepting this position, the facts are not siich as
to exclude the possibihty of some infective diseases
being the result of a combination of factors in which
micro-organisms have no special influence. Even with
regard to anthrax — the disease of all others which has
been absolutely proved to have a specific bacillus as its
cause, there are some experiments which would seem
,to invalidate that conclusion. For example, it has
been shown by Mons. P. Bert that compressed oxygen
kills all living things, but that infective material in
solution, such as scorpion venom, vaccine matter,
whether hquid, or dried and re-dissolved, resist the action
of compressed oxygen ; and from further experiments
he was led to infer that the active agent in vaccine and
in glanders is not a Uving micro-organism. He also
exposed anthracic splenic blood to the action of com-
pressed oxygen ; the blood retained its vkulent properties
intact, as proved by inoculation ; but in no instance did
the blood contain bacilli.

MM. Jaillard and Laplat likewise came to the follow-
ing conclusions, namely: — (1) That anthrax is not a
parasitic disease ; (2) that the presence of hacteridia is
to be considered as an epiishenomenon and not as a
cause ; and (3) that the fewer hacteridia the blood of
anthrax contains, the more virulent it is. Hence cases
of anthrax are described, some with and some without
bacilh. While experiments abundantly prove that
anthrax or splenic fever is an inoculable disease, those
of Brauell, Bouley and Bollinger, prove that the micro-
organisms found in the blood cannot be the carriers of
the vhus (nor the vhus itself), seeing that the blood

f2

68

The Animal Alkaloids.

not containing bacilli had been found to propagate the
disease ; that the disease may exist without the i)re-
sence of hacilli in the blood; that such non-hacillary
blood will induce the disease in other animals ; and
that even in such circumstances, organisms may de-
velop in the blood of the inoculated animal, and be
detected during life as well as after death. Bert sub-
sequently concluded that the blood in splenic fever
contains a toxic and virulent principle which resists
the action of compressed oxygen.**

Generally it appears to me that the isolation of such
a toxic principle as that first suggested by P. Bert,
points to the generation of a contagion, which is the
result of a living morbific process, and which may be
explained by the presence of some autogenetic toxic
agent circulating in the blood, and thus producing its
specific effect on the tissues and blood.

The experiments of Onimus with dialysed blood also
confirm this view ; and that the really jDoisonous material
is an albuminoid product not dialysable. As regards the
propagation of disease by bacteria as the active agent,
the so-called bacHlary tuberculosis, typhoid of the pig,
and recurrent fever, are all in the same category as
anthrax from this point of view. It has therefore been
inferred from such experiments that the virulence of
septinous substances is not dependent on micro-or-
ganisms, but that septinous fluids, after filtration
through porous porcelain, were still virulent. It has
thus been concliided that a fluid which can retain its
specific property after being filtered, boiled, evaporated

* "Comptes Rondus," Ixxxiv., p. 1130, May, 1877. Also Lewis's
" Memorial Volume," and Aitken, " Scionco and Practice of Medi-
cine," 7th edit., p. 375, vol. i.

Fallacies which beset Bacteiial Methods. 69

to di-yness, and the residue digested in cold and in
boiling alcohol, then redissolved, and again filtered,
cannot owe its toxic property to living organisms of
any kind.**

But more recent bacteriological methods, combined
with micro- chemical investigations, have furnished evi-
dence that various products of a poisonous nature are
produced as the result of the growth of bacteria. From
this point of view it may still be possible to reconcile
, the present conflicting theories as to the influence and
relations of micro-organisms to disease. But the
fallacies which beset • bacterial methods of investiga-
tions are such that trustworthy conclusions are difficult
to be arrived at.

The influences of life, of putrefactive processes after
life has ceased, of the results of growing germs in
hving tissue, and in sterihsed media, have aU been
used in drawing conclusions and in comparing results
which are not comparable. To apply and compare
conclusions derived from beef-tea, gelatine, and other
dead organic infusions in the chemist's flask or test-tube,
to the phenomena in hving beings, is an obvious fallacy.
The things have nothing in common, the factors are
not the same, and the phenomena of decomposition or
chemical change can never explain the phenomena of
disease. This is one great fallacy which runs through
much of the pathology which pertains to micro-
organisms in relation to disease. It is only when the
concurrent exercise of the functions which maintain hfe,
ceases, that a chemical change at once begins ; and
until that change sets in (either locally or generally)

* Aitkon, "Science and Practice of Medicine," 7th edit., p. 376'
1880.

70

The Animal Alkaloids.

the phenomena of putrefaction by the invasion of
micro-organisms are impossible. Here another fallacy-
introduces itself, namely, the elevation of the germ
facts concerned with j)utrefaction into a germ-theory of
disease.

Pure cultivations of specific micro-organisms have
been made with a view to ascertain the nature of
resulting chemical products ; but whether the products
thus obtained have or have not a chemical constitution
identical with those formed by the agency of the same
micro-organism when acting on living tissue is not
known. Brieger obtained a small quantity of a poi-
sonous base (typhotoxin) from cultivations of the
typhoid bacillus, which yielded reactions different from
the bases he had j)reviously isolated from putrefying
animal matter. He found that in some cultivations
the quantity of typhotoxin was very minute compared
with previous yields, and that in others it was alto-
gether wanting. The temperature and the compo-
sition of the material in which the cultivations are
made, exercise an influence on the results. When
the cultivation of a micro-organism is considered to be
successful, it must be at the expense of the organic
matter used as soil, so that the pabulum on which it
lives and is nourished, undergoes chemical changes.
If then a certain product is yielded on one occasion
and not at another, the inference is that its place is
occupied by a different product. Hence the result is,
to a certain extent, determined by the character of the
material in which the micro-organism is cultivated;
and so it remains doubtful whether identical chemical
products are formed by the same micro-organisms in
the living body and in artificial cultivations ; and the

Micro- Organisms as the Sole Cause of Disease. 71

difference in physiological action between the actively
toxic ptomaines obtained from recent cadavers, in
which death had been caused by an infective disease,
and the actively toxic ptomaines obtained from the
putrifymg cadavers of those who had died from non-
infective diseases, points to a dissimilarity between
some of the products yielded by pathogenic micro-
organisms, as compared with those yielded by putre-
factive bacteria ; and that the actual toxic products
.obtained were not the result of mere post-mortem
changes, but were the outcome of the disease from'
which the patient died.=^

Dr. Mann further gives an instance in which Koch's
comma-bacillus yielded on cultivation six distinct
ptomaines, three of which were actively poisonous ;:
and while two were probably specifically related to the
micro-organisms, four were common to them and to
the bacteria of putrefaction. Moreover, some highly
important experiments made by Bockhschf show that
a certain bacillus may under altered conditions produce
ptomaines of dissimilar chemical constitution and
physiological action ; and his experiments establish
the possibility of the formation of highly toxic pto-
maines by the combined action of disease and putre-
faction, possibly through the micro-organisms.

In the first edition of this book I too strongly
expressed myself as an unbeliever in any micro-
organism being the sole cause of any disease. But
there are exceptions ; and I have had the advantage
of practically studying and appreciating the evidence
now at our disposal ; and of coming to certain definite

* Dr. Dixon Mann, loc. cit.

t " Berichte dor deutsoh," "Chem. Gesellch.," 1887.

72

The Animal Alkaloids.

conclusions from personal observation, and to the
exclusion of mere theory. I had long since ceased to
believe in the powers of the microscope being able
alone to differentiate the minutest micro-organisms of
a like kind from each other. Microscopical differentia-
tion is indeed oftentimes absolutely impossible ; and I
have seen that it is only by cultivation of the micro-
organisms out of the body, by their careful isolation
from tissues, and from other organisms, and by being
able to demonstrate the same typical appearances
through a lojig series of cultivations, carried on under
certain definite conditions, that the differentiation of
micro-organisms becomes possible. Artificially culti-
vated growths are thus capable of being compared
directly, one with another, side by side ; and it is only
by such individual comparison that one is able finally
to appreciate differences in form and general appear-
ance of one growth as compared with another ; to
know that they are pure as to cultivation ; to be able
to place them in one or other class to which they may
belong ; and to broadly describe the j)hysiological and
pathogenic functions with which the micro-organism is
likely to be endowed.

"We are indebted to the distinguished bacteriologist.
Dr. Koch, of Berlin, for thus pointing out the great
importance and value of observing the general ap-
pearances, the modes and conditions of growth of
micro-organisms, and that these points are of much
greater value than mere microscopical and chemical
characters. Then we have the very important canons
Jaid down by Koch, by which we are able to determine
whether any definite micro-organism is the sole cause
of any disease. These canons are embraced in the

Workinrj Canons laid down by Kock.

73

following conditions, which justify our regarding a
given organism as the material cause — the contagium
vivum of a given malad3^*■'*

(1) The malady must have such distinct and con-
stant features, whether clinical or anatomical, as shall
enable it to be identified.

(2) The microphyte (or micro-organism) must be
itself distinguishable from all others by its size and
shape, its staining properties, but above all by its mode
,of propagation in " a pure cultivation " (i.e., artificial
separation from other organisms) and by the form,
colour and general appearance of the colonies it j)ro-
duces, and its mode of growth, both in plate cultivations,
in tubes, and in drop cultures.

(8) The organism thus identified must occur in the
blood or tissues, not merely on the surface (cutaneous
or intestinal) but below the epithehum, in the lymph
spaces or blood vessels, in every case of the disease in
question.

(4) It must not occur in the human body except in
cases of the particular disease in question. It may,
however, conceivably occur in other animals, without
giving rise to the same pathological symptoms, or in
air or water, as of course it does occur in the test-
tubes and plates of " pure cultivations," and in what-
ever media convey the contagion from one person to
another.

(5) When a pure cultivation of the organism is
introduced into the blood and tissues of an animal, the
phenomena (clinical and anatomical) of the disease in
question must be reproduced.

* Dr. Pye-SmitL in 2nd edition of Pagge's " Principlos and
Practice of Medicine," vol. i., p. 22.

74

The Animal Alkaloids.

(6) From that animal a " pure cultivation " must be
again capable of reproduction, from which another
animal may be again infected, and bo on.

These conditions in all their rigor I have seen
satisfied in the case of anthrax ; and with scarcely less
abundant proof I believe they have been satisfied as
regards relapsing fever, and in Malta fever.'*

Under these canons it is now held to be indisputable
that in certain forms of disease, definite micro- organisms
do play the part of the exciting cause. It is therefore of
importance to note the means which have been em-
ployed to arrive at this conclusion, so that the same
principles may be employed in working out the in-
vestigation of other diseases with which micro-organisms
are associated, but in which they are not yet proven to
be the sole cause of the disease. The mere presence of
a micro-organism in the body or in any of its cavities,
is of no value whatever from an etiological point of
view. Proof must be experimental in accordance with
the above canons.

"But of late evidence has been accumulating from
many various quarters, which almost, if not quite,
amounts to proof that the contagia of certain infective
diseases are living micro-organisms of extremely minute
size. There is in the first place the fact that in at
least two infective diseases — relapsing fever and an-
thrax— the constant presence of definite and characteristic
organisms has been positively demonstrated. To these
may be added tuberculosis, lupus, leprosy, Malta fever,
and perhaps also glanders, erysipelas, gonorrhoea, and
several forms of septicaemia in the lower animals and

* See account of Malta fever by Surgeon David Bruce, in
"Practitioner "for 1888.

Microbes in Relation to the Generation of Poisons, 75

in man. But constancy of occurrence and experi-
mental proof are not yet established, except as regards
anthrax, relapsing fever, and Malta fever."

A micrococcus has been established on good evidence
as the contagiitm vivum of erysipelas.

In variola and vaccinia, micrococci are present, but
they have not been proved pathogenic by experiment.
The same is true as regards dijihtheria. In pneumonia
several micro-organisms occur, but not constantly ;
.and which, if any, is the true pathogenic organism, is
still uncertain. The micrococci of gonorrhoea and of
ulcerative endocarditis are probably pathogenic, but
they are as yet less clearly identified, and the proof is
incomplete.

The baciUi v^hich have been found in enteric fever,
measles, cow-pox, sheep-pox, ague and cholera, are
still the subjects of controversy as to identity, con-
stancy, and pathology. That of tubercle is believed to
be constant, specific and pathogenic, but its relation to
much of what is clinically and anatomically called
tubercle in man is not fully established. Here the
first of the above conditions is wanting,*'*

It is obvious, therefore, that we have not yet succeeded
in tracing all infective diseases to micro-organisms; and
it is possible that further researches may even modify
the views now held by some with regard to the rela-
tions of the micro-organisms to diseases in which they
are regarded as the cause. This is especially so in
regard to the views now beginning to be entertained
as to the relation of -microbes to the generation of
poisons by them.

Hitherto the microbe has been looked upon as directly

* Dr. Pye-Smitb, loc. cit.

76

The Animal Alkaloids.

causing disease by its effects upon the tissue of the
patient ; but since chemical investigation has been
appUed to the processes of disease, and to the products
of putrefaction and fermentation, and to the products
resulting from the artificial cultivation of microbes in
nutrient media, we must now look upon many of the
symptoms which occur in consequence of the action of
microbes as due, not to their direct action on the
tissues, but to their indirect action in generating poi-
sons ; that they are, in fact, the active agents in the
formation of ptomaines.

Thus, the researches of Koch, Brieger, and others,
in bacteriology, have put the chemistry of putrefaction
and zymotic diseases on an entirely new basis.*

Dr. L. Brunton, in co-operation with Dr. Alan
Macfadyen, obtained important and interesting results,
which show that bacteria liquefy gelatine by means of
an enzyme, which can be isolated, and which will con-
tinue to act after the microbes have been desti'oyed ;
and like the ferments of the pancreas, this enzyme acts
most readily in alkaline solutions. Bacteria seem to
have the power of adapting themselves to the soil on
which they grow, and of manufacturing a ferment
suited to their needs ; for the same bacilli when grown
in starch paste instead of in gelatine or in beef- tea,
produced a different ferment, which would convert
starch into sugar, but would not act upon gelatine.

Similar results had been obtained by Bitter, who
found that Koch's cholera bacillus produces in meat
peptone, a peptonising ferment which is quite distinct
from the bacillus itself, and which continues active
after the bacillus itself is destroyed. Similar results

* Dr. Lauder Brunton in " Gulstonian Lectures " for 1889.

Relation of Microbes to Poisoning by Meat. 77

have also been obtained by Steinberg. Moreover, the
microbes themselves may be destroyed by a temperature
which does not destroy the activity of the ferment
which they have formed — as shown by experiments of
Bert and others (p. 67).

Dr. Brunton then proceeded to show the practical
apphcation of these results, as regards the relation of
the ferments formed by microbes, to poisoning by meat,
and to the prevention of disease from that source. It
is shown that meat which has become tainted by the
presence of putrefactive microbes, may possibly be
cooked sufficiently to destroy the microbes themselves,
while the ferments they have formed continue to de-
compose the meat and give rise to poisonous substances.
" We can thus see how a cold beefsteak pie, or other
cold meat, may become poisonous and produce serious
symptoms, although the same food may have been
eaten with impunity immediately after being cooked ;
for during the process of slowly cooling poisons may
have been formed in the meat, although there may
have been none in it immediately after it had been
removed from the oven, and any microbes present were
hkely to have been killed by the cooking. The fre-
quency with which meat, very slightly tainted, must be
eaten in summer, and the common rule of not eating
game at all until it is somewhat "high," as it is
termed, makes one rather wonder why poisoning by
ptomaines formed in such meat and game does not
occur more frequently, although I believe that it occurs,
in a slight degree, more frequently than people are
generally willing to allow."*

In further explanation of the danger of diseased

* "Brit. Med. Journal," June 15th, 1889, p. 1336.

78

The Animal Alkaloids.

meat, Dr, Brunton refers to some interesting exiieri-
ments by Bocklisch, whicli may explain the rarity of
ptomaine poisoning from this source. In experimenting
with pure cultivation of vibrio proteiis, better known as
" Finkler's bacillus," he found that it did not seem to
produce any poisonous substances, although it occurs
in the dejecta of patients who have been suffering from
sporadic cholera {cholera nostras or cholera Europcea),
and is supposed to cause the disease. It occurred to
him, however, that it is never present in the human
intestine as a pure cultivation, and that possibly the
presence of another bacillus along with it might cause
the formation of the poisonous products in sporadic
cholera. He therefore mixed some other putrefactive
bacteria with it, and found that the mixed bacilli
formed the highly poisonous methyl- quanidine.

In the same way it seemed not unlikely that cases of
acute poisoning by meat or game may be due to the
accidental presence of more than one kind of bacillus,
leading to the formation of specially poisonous j)ro-
ducts. More especially is this likely to be the case if
one of them is a pathogenic microbe which has ah-eady
produced disease in the beast or bird yielding the meat,
and a certain amount of decomposition of its tissues
before its death.

The belief is now entertained by many that choleraic
diarrhoea, Asiatic cholera, and typhoid fever, are all
due to microbes, although bacteriologists may not have
definitely settled the nature of the microbe in each
case. In choleraic diarrhoea and cholera it is probable
that a definite combination of more than one kind of

* Dr. L. Bruntoii, "British Medical Journal," June 22nd, 1889,
p. 1389.

Poisons isolated from the Cholm-a-Bacillm. 79

microbe acts to a great extent indirectly upon the
organism by producing chemical poisons in the in-
testine.

With regard to cholera, it was pointed out by Dr.
L. Brunton, in 1873, that the symptoms of cholera
" are exactly those of muscarine poisoning, and most
of the recent researches on the subject have tended to
show that these symptoms are due to the action of a
chemical poison which may act independently of the
microbes which produce it. Lewis and Cunningham
showed in 1874 that boiled cholera dejecta would still
cause diarrhoea, although any microbe present in them
must have been destroyed in boiling. Cantani and
Klebs have also obtained symptoms of poisoning from
sterilised cultivations of the cholera bacillus. Pouchet
obtained an oily base belonging to the pyridine series
from cholera stools, and Brieger got from pure culti-
vations of the comma bacillus in beef broth, in addition
to the common ptomaines of putrefaction, two poisons
which he regarded as specific products of the comma
bacillus. But none of the poisons which have been
isolated produce exactly the symptoms of cholera. In
Cantani's experiments, tremor, prostration, spasms,
and repeated vomiting were observed, whUe Klebs
noticed muscular contractions and alterations of the
kidney. The poison obtained by Pouchet irritated the
stomach and slowed the heart, while one of Brieger's
produced muscular tremor and cramps ; the other
lethargy, and feebleness of the circulation, with occa-
sional bloody diarrhoea. These facts render it probable
that the symptoms in cholera are not caused by a
poison formed by the action of the comma bacillus
alone, and it is evident that much more extended

80

The Animal Alkaloids.

investigation is required before the pathology of cholera
is accurately understood."

" In all such investigations, too, one must bear in
mind the possibility of the poison being formed not in
the intestines merely but ia the blood or tissues."**

So also with regard to typhoid fever, Dr. Brunton
observes that "the symptoms do not point so much to
the formation of a poison affecting the body generally,
as to the local action of the microbes upon the ia-
testine, although in some epidemics of typhoid the
intestinal symptoms are but slightly marked, whUe
bronchial irritation is very prominent. "Whether this
bronchial irritation is due to the action of a microbe or
to a ptomaine produced by it on the bronchial mucous
membrane I cannot say."

With regard to other infective diseases, Dr. Lauder
Brunton gives the following account of them, from the
bacteriological point of view and hi relation to animal
alkaloids : —

With regard to anthrax, " various theories have been
proposed as to the mode in which the anthrax bacillus
causes death. One idea is that the bacilli, by aggre-
gating together, block the capillaries and cause em-
bolism ; a second that they produce a ferment which
decomposes the tissues ; a third is that they give
rise to one or more definite poisons. It is quite
possible that all these theories may be, to a certain
extent, correct, and that each of them may represent
one factor in the production of the symptoms. The
third of them is probably the most important, however,
and the symptoms probably depend chiefly upon the

* See also Fagge's "Principles and Practice of Medicine," vol. i.,
p. 292.

Production of a rtomaine by Bacillus Anthracis. 81

formation of a poison. Indeed, Hoffa has obtained
from pure cultures of the bacillus anthracis a ptomaine
which subcutaneously injected produces the symptoms
of anthrax, and death ; but it is not unhkely that the
presence of a ferment may aid the anthrax bacilhxs in
the production of a poison. Pasteur showed that the
anthrax bacillus did not produce a ferment which was
capable of causing the disease when injected, for by
filtering the blood of animals suffering from anthrax
through porous cylinders, and thus keeping back the
bacilli, he obtained a filtrate which was inactive. In
all probability, any ferment which the bacilli had
formed would have passed through in the filtrate, and
would have produced the ordinary symptoms after
injection ; but Nencki proved this in a way still more
free from objection, for he inoculated gelatine jelly
with anthrax bacilli. These liquefied the gelatine and
fell to the bottom, and the clear liquid which remained
above produced no effect on animals. Wooldi-idge,
indeed, claims to have transmitted the toxic power of
anthrax to vegetable albumen, organisms being absent.

"These experiments appear to prove that if the
anthrax bacilli produce a ferment at all, that ferment is
incapable of producing the disease. At the same time
one must remember that after the injection either of
the vegetable ferment, papain, or of sterilised septic
blood into animals, Eossbach and Eosenberger found
their blood swarming with bacilli. This observation
seems to show that the ferment had rendered the
blood more suitable for the rapid growth and multipli-..
cation of the bacilh."

The late Dr. Wooldridge found that when anthrax
baciUi were cultivated in beef-broth, and the bacilli

82

The Animal Alkaloids.

themselves removed by filtration, the filtrate (containing
as it did the in-odncts which they had formed during
their growth) rendered an animal into which it was
injected proof against anthrax inoculated afterwards.

Pasteur and Perdrix found that the blood of animals
suffering from anthrax, when sterilised and injected
into rabbits, appeared to protect them against sub-
sequent inoculation.

In piieiyeral fever it is probable that the production
of ptomaines in the tissues plays an important part,
for Bourget isolated several toxic bases from the viscera
of a woman who had died of this disease. This would
not by itself prove that these poisons had been formed
during life, and were not simply the products of putre-
faction, but he also obtained from the urine of patients
similar bases which were highly toxic, and killed frogs
and guinea-pigs when administered by injection. The
amount of poison in the urine was greatest when the
symptoms were most severe, and diminished when the
patients recovered. This fact appears to indicate a
connection not only between the poison and the disease
but between the gravity of the disease and the amount
of poison.

With regard to tetanus, when animals are inocu-
lated with matter taken from suppurating points or
with the medulla of animals which have died of tetanus,
the disease is reproduced, and on microscopic examina-
tion a bacillus has been found to be present. From
pure cultivations of this bacillus Brieger obtained four
poisons. The first, tetanirie, produces tetanus in mice
when injected in minute quantity. Another, which he
has not named, also causes tetanus, along with a free
flow of sahva and tears. Another, tetanatoxine, first

Tetanus, Diphtheria and Rabies Poisons. 83

produces tremor, then paralysis, and lastly violent
convulsions. A fourth, spasmotoxine, causes severe
convulsions both clonic and tonic. This discovery of
Brieger renders it probable that the convulsions in
tetanus are due to the action of a poison, but we
cannot at once assume that this poison necessarily
circulates in quantities with the blood, especially as
the flesh of animals which have died of the disease
may be eaten with impunity. It is quite possible that
it may be formed either entu-ely or chiefly in the nerve
centres, and that only very small quantities of it pass
into the general circulation.

From cultivations of diphtheria Eoux and Yersin
have obtained a soluble poison which may cause the
symptoms of diphtheria in various degrees of intensity
according to the dose. A large dose may cause rapid
death, a smaller one may produce paralysis, ending
fatally, while a still smaller one may cause only tem-
porary paralysis."

*' This poison, however, is not a ptomaine, that is, it
is not of an alkaloidal nature. It appears to be rather
alhed to ferments, and is destroyed by boiling for ten
minutes. The results of experiments already made
render it hopeful that it may be possible by its means
to confer immunity from the disease, but this is not yet
certain,"!

With regard to hydrophobia or rabies its virus is still
unknown. I It is only presumed by analogy to be a

* Eoux and Yersin, "Annales de I'Institute," Pasteur, 18S8,
Nos. 11 and 12.
t Dr. L. Brunton, loc. cit., p. 1395.

X " Croonian Lecture delivered before Eoyal Society," by M. Eoux
on behalf of M. Pasteur, June 8th, 1889, "British Medical Journal,"
p. 1269.

O 2

84

The Animal Alkaloids.

microbe, ■whicli no one yet has been able to isolate.
Nevertheless, the poison is daUy being "attenuated"
and made to pass through various stages of virulence.
This is done through the inoculation of living rabbits,
the virus being unable to be cultivated artificially in
flasks or tubes. Thus, Pasteur has arrived at this con-
chision, namely — that the active agent in preventing
hydrophobia is a chemical substance (possibly formed
by an unknown microbe) and upon this idea his plan of
preventing hydrophobia is based.

Am-ep says that he has isolated a ptomaine from the
brain and medulla oblongata of rabbits suffering from
a severe form of rabies. This ptomaine is very poi-
sonous, and minute doses cause the earlier symptoms
of rabies, while larger doses cause the phenomena
usually observed in the later period of the disease. A
gradual habituation of the animal to small doses of the
ptomaine produced a certain degree of immunity.*

The greatest source of danger from microbes is now
believed to exist in the poisonous products which they
manufacture ; and it is in the artificial cultivations in
flasks and tubes that the poisonous products of the
pathogenic activity of the microbes are to be sought
for.

It -has been shown that many pathogenic microbes
manufacture poisonous products. The microbes of
typhoid fever, of Asiatic cholera, of blue pus, acute
experimental septicaemia, and of diphtheria, aU belong
to this class.

It is therefore argued that in infectious maladies the
cause of death is poisoning, and that the microbe is not
merely the means of spreading infection, but it is also
* "British Medical Journal," Feb. 9th, 1889, p. 319.

Immunity conferred by Protective Inoculation. 85

the maker of the poison. On such facts the principle
of protective inoculation by chemical substances rests.

" By introducing little by little into the bodies of
animals these chemical substances produced by patho-
genic microbes, such, for instance, as that of acute
septicemia, in such a manner as to avoid causing
speedy poisoning, but so as to gradually accustom the
animal to its presence, it becomes refractory not only
to toxic doses, which would have originally caused
death, but also even to the microbe itself; and the
immunity which hitherto we could only give by the
introduction of a hving virus into the body we can now
effect by the introduction of a chemical substance into
the tissues, and these inoculable substances are exactly
those which we have observed in infectious diseases as
being the cause of death. In large quantities they kill,
in smaU they confer immunity. These experiments on
protective inoculation by means of soluble substances
without microbes have been successful in various
maladies, and we may be allowed to hope that thek
field of utility will become much wider."

The question now arises — has the animal, the recipi-
ent of a sufficient dose of these products, become refrac-
tory in consequence of their being present in the tissues,
and thus preventing the growth of the microbe ? Upon
this point, while we do know that in cultivation the
growth of certain microbes is arrested by the accumu-
lation of the products which they form, we must
carefully avoid forming a definite opinion as to what
happens in the living body upon the basis of phenomena
which have been observed to take place in culture tubes.
For example, if we take a little blood from a sheep
which has been rendered refractory to anthi-ax, and

86

The Animal Alkaloids.

place in it anthrax bacilli, they will grow there rapidly
and abundantly, thus showing that there is in the blood
of this protected animal no substance capable of de-
stroying the life of the bacteria. This experiment is, of
course, an extremely crude one, since from a chemical
point of view there is an enormous difference between
(hving) blood while still retained in the living vessels,
and the same blood drawn from the body and placed in
a culture flask. If any positive result were obtained, it
could only be from an absolutely enormous chemical
change in the composition of the tissues.

But in addition to the chemical there is the physio-
logical question to be dealt with, and M. Eoux shows
how by artificial necrosis of the tissue the virus of
anthrax is able to gain a footing in a rabbit — an ani-
mal which by nature is refractory to this disease if its
tissues are sound,

A distinction must now therefore be made as to (1)
diseases which acknowledge as a cause agents devoid
of life, which are essentially chemical — as are the
animal alkaloids {■ptomainee and leucomaines) — alkaloids
found during the decomposition of animal matter, and
also during the process of life— healthy and morbid —
agents producing acute septic intoxication without the
presence of a single micro-organism in the tissues, sufl&-
cient toxic material being developed on a large exposed
surface, whence being absorbed, may give rise to the
death of the patient, as occurs in cases of what used to
be called hospital gangrene, where a large surface of
suppurating tissue being estabhshed numbers of putre-
factive organisms grow and induce septic poisoning.
(2) Diseases which are also essentially chemical, but
the agents of which act catalytically after the manner

Classification of Micro-Organisms. 87

o{fen7imits, and which are therefore really zymotic. Such
are associated with the presence of minute organisms,
which in some cases are shown to be the cause of the
fermentation — ^just as the bacterium, lactis has been shown
by Lister to be the active agent in determining the
lactic acid fermentation on souring milk.*

Pasteur has shown that alcoholic and butyric fer-
mentation acknowledge a similar agency. Other ex-
amples are the micrococcus urincB, causing the ammoniacal
fermentations of urine, and the micrococcus in putrid
meat and fish to which phosphorescence-like appearance
is due, and forming aerobic zoogloea. That putre-
faction is set up by organisms, is demonstrated by
Lister's method of treating wounds, seeing that the
discharges from them remain sweet so long as the
organisms which induce decomposition and fermenta-
tion can be excluded by the appropriate dressings and
antiseptics. Septicaemia is an example of a zymotic
disease from this point of view.

The chromogenic micro-organisms are characterised by
their power of producing colours of various hues. They
are all aerobic, and only produce pigments when in free
access of air. Transplanted specimens always produce
the same pigments.

The patJwgenic micro-organisms are those associated
with disease.

The physiological effects of the micro-organisms have
been classified by Fliigge as (1) sejjtic or putrefactive,
(2) zymogenic or fermentive, chromogenic or pigment-
forming, and pathogenic or those productive of specific
infective diseases. f

* "Pathological Society Transactions," 1877-

t "Fermenti und Micro-parisiten," Leipzig, 1883.

88

The Animal Alkaloids.

Whatever may be proved to be the relation of these
micro-organisms to the j)roduction of chemical and
poisonous products, as the result of their life in arti-
ficial cultivations, or in the living body — the researches
of Selmi, Gautier, Peter, Brieger and others, amply
explain the formation of poisonous animal alkaloids,
and of still more poisonous extractive compounds
— the X, y, z's of morbid anatomy and pathology —
by means alone of the physiological processes of life
within our bodies which are continually at work, as
explained in the previous pages. They show us that
the living being is constantly manufacturing in his own
tissues, agents which can produce disease and even
death. Hence it must be admitted that " the hving
tissue elements of the body itself play a much more
important part in the elaboration of septinous and
allied poisons than what has been of late ordinarily
ascribed to them;*'* and neither have we " yet grasped
the infinite potentialities of molecular energy, which
must play so great a part in pyrexia, in living func-
tion and in growth. f How very interesting then
becomes the study of the " animal alkaloids " and the
"extractives" in their chemical, toxical, and patho-
logical relations ; and particularly of the " leuco-
maines " and the " extractives " as they are found in
the urine. Their variations in quantity and quahty in
that excretion as indications of varying conditions of

* T. R. Lewis, M.B., "Microscopic Org-anisms found in the Blood,"
Calcutta, 1879, p. 57, also, " Memorial Volume of bis Collected
Works," published by subscription and sold by Mr. 11. K. Lewis,
London.

t "A sketch of an hypothesis towards vito-chemical methods in
Pathology and Therapeutics," by W. H. Pearse, M.D., Prov. Med.
Journal, 18S8.

A Method of Estimating the Constituents of Urine. 89

health and disease call for the most searching methods of
investigation with all the modern appliances of the day.**

To my friend and colleague, the late Professor de
Chanmont, I am indebted for the following method of
determining (approximatively and by exclusion) the
specific gravity of the "extractives" and other sohd
constituents of the urine, which he kindly allowed me
to publish in the first edition of this work.

The results are interesting and instructive, inasmuch
as when the calculations from the daily amount of
urine are regularly worked out and compared day by
day, the method of thus estimating the constituents
that go to make up the total solids and specific gravity
furnishes an excellent check upon the chemical analysis.

Professor de Chaumont's method of procedure is as
follows : —

1. Collect measure and record the total quantity in
cubic centimetres of the urine passed during twenty-
four hours. Let it be 1850 cc.

2. Note its specific gravity. Let it be 1023.

3. Chlorides. — Determine their amount by noting
how many cubic centimetres of standard nitrate of
silver solution are required to precipitate the chlorine in
1 cc. of urine. The result multiplied by 1-65 (chloride
of sodium) gives the amount of chlorides, seeing that
each cc. gives one of chlorine.

If, for example, 1 cc. of this urine took 5-4 cc. of
standard nitrate of silver solution, that multiphed by
1-65 gives 8-91 of chlorides per 1000 cc.

* See also Parkes "On the Urine"— a book which ought to be
republished by the New Sydenham Society. No other book on the
nrine surpasses it in tho scope, accuracy, and care with which the
observations have been made.

90

The Animal Alkaloids.

4. Phosphates. — Similarly 50 cc. of this urine took
16 cc. of uranic nitrate standard solution, equal to 1"6
of phosphoric acid per 1000, which multiphed by 2
gives 3-20 as the amount of phosphates.

5. Urea. — Similarly 10 cc. of this urine took 20 cc.
of mercurial solution which is equal to 20 of urea per
1000.

6. Glucose. — 10 cc. of Fehling's solution took 4-2
of urine, equal 11*9 per 1000.

Dr. de Chaumont further calculated that the clilo-
rides in solution give (by experiment) 8 degrees specific
gravity for every 10 parts per 1000 ; that phos-
phates give about 4 degrees for every 10 parts per
1000 ; that urea gives 3 degrees specific gravity for
every 10 parts per 1000 ; that glucose gives 4 degrees
specific gravity for every 10 parts per 1000 ; the sul-
phates give about 5 degrees ; and the sulphates may
be assumed to be about half the amount of the phos-
phates.

Therefore make all these several multiphcations ; add
up the results and find the difference between the total
and the excess of the specific gravity over 1000.
Amount of Chlorides 8-91 x -8 = 7-13
„ Phosphates 3-20 x •4 = 1-28
„ Sulphates 1-60 x •5 = 0-80
„ ,, Urea 20-00 x -3 = 6-00

„ Glucose 11-90 x -4 = 4-76

Total 19-97 =

specific gravity due to solids less extractives.

The specific gravity of the total urine was found to
be 1023, then 23-00—19-97 = 3-03 = the residue of the

Weight of the Unknown Extractives.

91

specific gravity which may be taken as representing the
X, y, z's (the unknown extractives). In these extractive
matters recent investigations have discovered powerful
poisons.

Assuming these to be at least equal to the weight of
the glucose or other extractiform material, namely, 4
degrees specific gravity for 10 parts per 1000 of weight,
dividing that residue, therefore, by -4 will give the
weight of the x, y, z's (the unknown extractives) ap-
proximately. Therefore 3-03 = residual specific gravity
divided by -4 = 7"58 per 1000 to be added on to the
weight of the other things per 1000, thus giving 53*19
as the total solids per 1000.

The daily products would then appear in the follow-
ing tabular form : —

Drine (June, 1887) = 1850 cc, specific gravity, 1023.

Per 1000

Sp. Gr.

Total in
1850 CO.

Chlorides

8-91

7-13

16-48

Phosphates ....

3-20

1-28

5-92

Sulphates

1-60

0-80

2-96

Urea

20-00

600

37-00

Glucose .....

11-90

4-76

22-01

Extractives ....

7-58

8-03

14-02

Total Solids* .

53-19

23 00

98-39

* There is a source of error (not material) namely, that no allowance
has been made for precipitated uric acid, as urates.

92

The Animal Alkaloids.

53-19

Eatio of solids to specific gravity = = 231.

23

The recognition of toxic urine in relation to surgical
operations "on the urinary organs," is of great practical
importance.**

Mr. Harrison, of Liverpool, has shown that the
rigors and fever which sometimes attend catheterism
and internal urethrotomy, are symptomatic of poisoning
rather than of shock — of poisoning by material furnished
dhectly from the urine. Free-flowing healthy urine
may be regarded as absolutely innocuous ; so that when
it makes its way over a fresh cut surface, or out of a
cavity, just as fast and uninterruptedly as it flows over
or in it, it need cause no apprehension. On the other
hand, when pent up in a wound or cavity, it is apt to
be speedily converted into a most destructive poisonous
agent. Urine-fever is thus easily set up by catheterism
and by the operation of internal urethrotomy. The
decomposing urine, or otherwise morbid urine, provides
septic material of a kind sufficient to cause the urinary
fever ; and in illustration of this point the researches
of Dr. Bouchard, at the Hospital Lariboisiere, on
" Toxic Urine," are of much interest ; and at p. 256 of
the Eeview, Mr. Harrison gives the following digest of
Dr. Bouchard's papers, which were presented to the
" Societe de Biologie " in 1882.

In these papers Bouchard showed that alkaloidal
substances were constantly present in the urine in
certain infective disorders, and that these alkaloids

* Reginald Harrison, F.R.C.S., Surgeon to Liverpool Royal In-
firmary, and Lecturer on Clinical Surgery in Victoria University,
in "Liverpool Medico-CHrurgical Journal," vol. vi., p. 251.

Summary of Bouchard's Researches.

93

were of intestinal origin. That is to say, they were
substances produced in the intestinal canal, and were
analogous to the i^tomaines. Subsequently these al-
kaloids were found to be present in normal urine.
Dr. L. Brunton looks upon much indican in urine as an
indication for a mercurial purgative. It shows that
bacteria are active in the small intestines, and that
albuminous matters are undergoing rapid decomposition
there.f Bouchard found the same alkaloids present in
the fsBces ; and he divided them into two groups : — (a)
Those soluble in ether, and {b) those soluble in chloro-
form. He found that when present in large quantities
in the fasces, they were also present in proportionally
large amount in the urine. The following are his
conclusions : —

(1) In health alkaloids exist in the Hving subject.
(2) These alkaloids arise in the intestinal canal, through
the action of putrefactive intestinal organisms. (3) The
alkaloids of normal urine represent a practical part of
these intestinal alkaloids, absorbed by the intestinal
mucous membrane, and excreted by the kidneys. (4)
Diseases augmenting intestinal alkaloids, augment par
consequence the urinary.

In his next paperj he determined experimentally the
effects of normal urine on rabbits, and found that the
same doses produced different effects according as the
individual furnishing the urine was in health or not ;
also that the toxicity varied in different individuals,

* "De I'origine intestinale de certains alkaloides normaux ou
pathologiques," par Ch. Bouchard. "Kev. de Med.," 1882, tome ii.,
p. 825.

t " Gulatonian Lectures," 1889, loc. cit.

X Recberchoa exporiinentales sur la tosicite des urines uormales,
"Comptes Eendus," 6 Dec, 1884.

94

The Atiimal Alkaloids.

that the symptoms depended on several distinct sub-
stances. He proved that the symptoms were not due
to the water of the urine, nor to the urea, uric acid,
creatin, salts or volatile matters. Further, he showed
that the alkaloids soluble in alcohol differed in their
effects from those insoluble in alcohol ; and that
although there might be five or six different substances
present, they could symptomatically be arranged in
two groups — a convulsive and a narcotic ; and he
concluded that the symptoms in different cases of
uraemia might be explained by these groups being
present in the blood in varying proportions.

More recently Bouchard has brought forward some
further facts with regard to the urinary alkaloids and
their properties.** He defines a toxic or a unit of
poison as that amount of poison required to kill one
kilogram of living matter, e.g., of rabbit. The urotoxic
is that quantity of urinary alkaloids capable of killing a
rabbit weighing one kilogram.

The symptoms of urinary toxsemia produced by in-
troducing urine into the veins of a rabbit, are in the
order of thek occurrence : — (1) Contraction of pupils.
(2) Acceleration and diminished amplitude of the re-
spu'atory movements. (3) Increase of urine. (4) Fall
of temperature. (5) Diminution and final abohtion of
reflexes. (6) Convulsions usually with coma ; and
(7) death. The action of the heart and the electro-
contractihty of the muscles persisting for a time after
death.

* Sur les poisons qui existent normalment dans Torganisme et
en particuliere sur la toxicity urinaire, "Gazette Hebdoniadaire,"
Avril, 1886; " Sur la variations de la toxioite urinaire pendent la veille
et pendent la sommeil."

JJrinarij Poisons in Sleepiiuj and Waki.ntj lJuurs. !J5

The fall in the temperature is clue not to increase in
the loss of heat, but to diminution of heat production.
The urotoxic co-efficient in man is -465 ; in other
words, for each kilogram of body weight enough poison
is excreted in twenty-four hours to kill -465 grammes
of living matter ; or in two days and four hours a man
excretes enough to kill himself.

During eight hours, if asleep, only from one-quarter
to one-half as much poison is excreted as during the
same period when awake. If the day be divided into
three periods of eight hours each, the proportional
quantities of poison excreted are : — Asleep, 3 ; early
waking period, 7 ; late waking period, 5. The urine
after sleeping and waking hours also differs qualitatively
as weU as quantitatively.

The alkaloid of the urine of sleep is convulsive, that of
the waking urine narcotic.

The urinary poisons of the sleeping and waking
hours are not only different, they are physiologically
antagonistic. Fasting increases the toxicity of the
urine, probably because then the individual lives on his
own tissues ; and these are relatively more difficult of
oxidation than the ordinary food, and are less com-
pletely oxidised. Labour greatly diminishes the toxicity
of the urine, so does also the breathing of compressed
air.*''

"When we consider how many conditions influence
the nature of the products of albuminous decomposition,
we cannot be astonished to find that very different sub-
stances have been obtained by different experimenters.

* Influence de I'abstinence dutravail musculaire, et de I'air
coraprine sar la toiicite urinaire, "Gazette Hebdomadaire," le
19 Mai, 1886.

96

The Animal Alkaloids.

The chemical operations required to isolate the different
products are so comphcated and laborious that most
experimenters have been satisfied with obtaining " ex-
tractiform bodies," and have not as yet attempted to
crystallise them.'*

A question has also arisen with respect to the actively
toxic products obtained from the bodies of patients
dying from specific diseases, namely : — What relation
have the toxic alkaloids so obtained, to the diseases
from which the respective patients have died ? Physio-
logical experiments have shown that actively poisonous
cadaveric alkaloids (ptomaines) have not been found in
recent animal tissues, so as to be isolated in the crystal-
line form as definite chemical products. The physio-
logical product cJioline is the only basic product found
within 24 to 48 hours after death (Brieger and Dixon
Mann). No actively toxic base has been obtained in
this early post-mortem period — a fact of great im-
portance in a medico-legal point of view. No basic
product occurs at this early period, which can be
confounded with any vegetable alkaloid administered
criminally. Choline, which is but feebly toxic, is not
found after putrefactive changes have been in j)rogress
for about a week; and with its disappearance the
actively poisonous ptomaines begin to form — the out-
come of advanced putrefaction, for the formation of
which the access of oxygen is necessary.

Alcoholic extracts, prepared from recent animal
tissues, contain many physiological products, some of
which have more or less toxic properties. Many pto-
maines are toxic when impure (extractives), but lose
their poisonous properties when freed from other pro-
t Dr. Lauder Brunton, loc. cit., p. 281.

Key to Idmtijication of Pathogenic rtomaines. 97

ducts ; so that comiDaratively few of the pure crystalline
cadaveric alkaloids are actively toxic (Dixon Mann).
These facts point to the existence of other substances
which as yet have not been identified ; and Dr. Dixon
Mann is inclined to believe that some of these products
are volatile; because, in the early stage of the operations,
•when worliing at the isolation of the ptomaines from
the organs of patients who had died from infective
diseases, he experienced the peculiar effects of drowsi-
ness, lassitude and mental depression, characteristic of
such poisoning.

The key to the question of identification of the
pathogenic ptomaines is to be found in (1) chemical
constitution ; (2) physiological experiments. In the
latter investigations it is necessary to recognise the
obvious difference between the introduction of a lethal
dose of a ptomaine into the circulation of a healthy
animal ; and the gradual accumulation and progressive
action of morbid leucomaines developed in the course of
disease. Another difficulty comphcates the judgment
arising from the unequal susceptibihty to the action of
ptomaines that has been proved to exist amongst various
kinds of animals ; and a stiU greater difference probably
exists betwixt animals and human beings.

The physiological experiments, however, demonstrate
on the one hand, the strong lethal potency of animal
alkaloids obtained from bodies dead from ' infective
diseases ; and on the other a distinct difference in
physiological action between these products and the
actively toxic ptomaines obtained from putrefying,
animal tissues — differences which are not the result of
post-mortem changes.

To determine the presence, the nature, the pliysio-

H

98

The Animal Alkaloids.

logical effects, and the place in Pathology of the "pto-
maines," the " leucomaines," and the " extractives," is
a difficult investigation, hecause of the tedious and pro-
longed chemical processes that are required, and the
subsequent experiments on the products.

The main difficulties are these : — (1) It is obvious
that the newly formed substances being antagonistic to
life, as soon as a lethal amount has been formed, death
results. If the. substance is very active, the quantity
necessary to cause death will be small, and being dis-
tributed throughout the organism, will be difficult to
isolate. (2) These alkaloidal bodies are very unstable,
and the means taken for their identification, unless
great care is exercised, may hasten their transformation
into other combinations of a totally different nature.
(3) The post-mortem changes which intervene ere the
investigation can be commenced, tend to comphcate
matters by introducing other chemical changes, and
possibly destroying the identity of the combinations
previously formed. In the face of these difficulties it
has hitherto been deemed futile to attempt to demon-
strate, in the dead body, the presence of pathological
animal alkaloids {i.e., morbid leucomaines) supposed to
have been formed before death.

Nevertheless the influence which chemistry has
exerted on the Science of Pathology during the past 50
years, cannot be overrated, and points to the conclusion
that the microscopist must give way, and share or divide
his work with the chemist. The processes of chemistry
are now far in advance of microscopical revelations, so
that hencefortli the results of microscopic work,
especially as regards micro-organisms, must be more

• Dr. Dixon Mann, loc. cit.

Question as to Usefulness of Scientific Missions. 99

controlled or checked by the chemist than they have
hitherto been. Hence it is by chemical, combined with
biological and bacteriological methods, that we must
look for the discovery of the many factors in the causa-
tion of diseases, and for the power of preventing or
removing diseases. The physiological symptoms of the
infective diseases appear to be thus far traceable to
definite chemical compounds, to animal alkaloids ; and
that to the action of such poisonous compounds during
Ufe, the special characteristics of the disease are to
be traced. For it has been shown that disease can be
communicated by such j)oisons in the entire absence of
living micro-organisms.

" Scientific missions inspu-ed in the interests of 'germ
pathology ' have visited India, Egypt, and Southern
Europe, in the quest of a specific microbe for cholera ;
but they have all signally failed. Dr. Koch, the chief
of one of them, thought he had found the pathogermic
entity of cholera ; but, confronted and constrained by
facts, this eminent bacteriologist has felt himself obliged
to admit that his ' comma bacillus ' does not directly
engender the disease ; but that it may do so indirectly
by the intervention of a ' ptomaine ' which it is sup-
posed to secrete. But this impUes two suppositions,
namely :— (1) The existence of a specific bacillus which
has not yet been discovered;*' (2) the supposition
merely of the secretion of a ' ptomaine ' by that bacillus
which is just as far from being demonstrated, as already
explained."!

* Dr. A. M. Brown, loc. cit.

i Transactions of a " Gommittee convened by the Secretary of
State for India "to consider a Eeport by Drs. Klein and Gibbes
entitled ''An inquiry into the etiology of Asiatic Cholera," July,
1885. Also Dr. Lewis in " Lancet" of Sep. 20th, 18S4, p. 513.

H 2

100

The Animal Alkaloids.

The attempt to reproduce the disease in animals by
inoculation or otherwise by the supposed specific bacilhis
has failed; while the experiments and observations
hitherto made leave the question of the genesis of the
disease quite unsettled.** At the same time " while
some of the points of contention regarding microbes
appear to be proved, others are only probable, and they
are neither universally nor unconditionally accepted.
The exclusively causal agency of bacilli in the diseases
with which they have been associated, although ex-
tremely plausible, is not conclusively proved (except
as regards anthrax and relapsing fever and Malta
fever) ; and a great number and variety of experiments
of contrast are yet needed to satisfy a just scepticism,
surrounded as the investigations are by the many falla-
cies, to some of which I have referred."!

Another feature of these microbes which warrants
continued scepticism as to the powers of the microscope
to differentiate them is brought out very conspicuously
by the attempts to photograph them, namely : — That
they are all so much alike that no sufficient distin-
guishing features exist amongst them for differentiation.
Their family likenesses are strikingly similar ; " and
the results of photography are so unsatisfactory, that
even Koch has abandoned it in heu of accurate drawings
made in the usual way. "J

The direct advantage of the scientific missions
avowedly sent to discover " something " is very much

* "Special Pathological Anatomy," by Ziegler and Dr. D. Mao
Alister, p. 290, Macmillan and Co. ; also Klein's " Micro-organisms
and Disease."

t Sir Andrew Clark, Bart., M.D., Lumleian Lectures, " Lancet,''
April 4tli, 1885.
X Klein, loc. cit., p. 14.

Discoveries are Slowly Elaborated.

101

open to question, and to doubt, as to their usefulness.
If one is sent to seek for some specific thing, there may-
be many and varied inducements to find it, or some-
thing which may meet the requirements of the mission.
Discoveries are not made in this way. No single man
has yet accomphshed by himself any notable discovery —
not even when he sat himself down more or less com-
fortably to seek for one. Discoveries have usually
been the outcome of " many thoughts of many minds,"
working through many cycles of time. Thus it is that
discoveries are very slowly and as it were quite un-
consciously elaborated — one man's work preparing the
way for advances towards ultimate discovery by another.
It in no way detracts from the great discovery of
Harvey that the way had been paved for it by the
discovery of the valves in the veins by Sylvius and
Fabricius, and by that of the lesser circulation by
Servetus. Neither is the merit of the subsequent dis-
covery of the lesser circulation by the great anatomist
Malpighi, in any way lessened by the fact that the
existence of the channels first seen by him, was as
clearly pointed to by Harvey's reasoning, as the ex-
istence of Neptune by the calculations of Le Verrier
and of Adams. So also there can be no doubt that
Kepler's elaborate series of measurements, and subse-
quently the measurements ol Picard, as well as the
discussions of Wren, Halley and Hooke, led up to and
enabled Newton (by calculating from Kepler's laws), to
arrive at the great discovery of the law of gravity, which
up to that time had been merely a conjecture.*''

But there is still another point to be noted as regards
discoveries, namely : —That when discoveries are made

* "Encyclopoedia Britannica," art. Nowton.

102

The Animal Alkaloids.

it is not always easy to appreciate their value, or even
to comprehend their significance, and far less to fore-
cast the numerous and important results to which, in
the future, they may lead, or the place they will finally
hold in the circle of the Sciences. Time is an imj)ortant
element in their evolution, their development, their
influence and their powers of usefulness.

Therefore it is that we may look forward with con-
fidence to the future for much thoughtful work to help
onwards those discoveries which have yet to come,
alike in bacteriological and in micro-chemical methods.
I have elsewhere pointed out'' the very great differences
of opinion entertained regarding the identity and causa-
tion of enteric fever in India and Egypt and even in
this country ; and esj)ecially in India do we require
some one hke Su* William Jenner who will teach us to
differentiate the fevers prevaHing there. The methods
of Jenner combined with bacteriological and chemical
methods may help to do this.

Could we but climb some pathological Pisgah and
be allowed to stand as Moses stood, when he was per-
mitted to view the promised land, we too might rejoice
in the bright and certain prospect that there lays
before us a great and glorious future for Pathology and
for the Science and Practice of our Art.

* "Science and Practice of Medicine," 7tb edit.

Appendix.

103

APPENDIX.

Ptomaines in Infective Fevers. f

Aethur p. Luff, M.B., B.So., F.C.S., Lecturer on
Medical Jurisprudence and Toxicology at St. Mary's
Hospital School, has experimentally investigated the
relation of ptomaines or animal alkaloids to some of the
infective fevers. He has examined the urine in typhoid
and in scarlet fever, so as to determine the presence of
animal alkaloids or the formation of ptomaines in that
secretion in these diseases ; and he describes the fol-
lowing method for their extraction— a method which
presupposes that the animal alkaloids are soluble in
ether — and that no heat is employed in the process.
The details of the method are : —

1. A large quantity of urine is to be rendered alka-
line by solution of sodium carbonate.

2. The alkahnised urine is to be thoroughly agitated
with half its bulk of ether.

3. After standing, the etherial solution is to be fil-
tered and agitated with solution of tartaric acid, which
settles to the bottom of the vessel, and carries in solu-
tion any animal alkaloids in the form of soluble tar-
trates.

* See pages 55, 57, 91 to 96 of text.

t British Medical Journal, July 27th, 18S9, p. 193.

104

The Animal Alkaloids.

4. The tartaric acid solution is separated from the
ether ; is also rendered alkaline by solution of sodium
carbonate ; and is again agitated by half its bulk of
ether.

5. After standing the ethereal solution is removed,
and the ether allowed to evaporate spontaneously.

6. The residue is to be dried over strong sulphuric
acid, and then examined for animal alkaloids.

Normal urines yield no animal alkaloids. Therefore
if animal alkaloids are extracted by this proce!,s8 from
urines of patients suffering from any infective fever,
such an alkaloid has been produced within the system
during the course of the fever — a morbid leucomaine.
The patient must not be at the time taking any alkaloid
or antipyretic remedy.

In typhoid fever and in scarlet fever Mr. Luff has in
each discovered a new animal alkaloid. In typhoid he
obtained a white crystalline substance which exhibited
all the properties, and gave aU the reactions of an
animal alkaloid ; and was converted into a hydrochlo-
rate by dissolving in very dilute hydrochloric acid.

The reactions were as follows : —

Phosphomolybdio acid ... ... Gave a widte precipitate .

Phospliotungatic acid nil.

Mercuric and potassium iodide ... ,, dense yellow precipitate.

Iodine solution „ brown precipitate.

Tannic acid , yellowish-brown precipi-
tate.

Picric acid ,, dense yellow precipitate.

Platinic chloride nil.

Gold chloride „ dense yellow precipitate.

No known animal alkaloid gives such reactions.

In scarlet fever the animal alkaloid was in the form

Appendix.

105

of a white semi- crystalline substance, soluble in water
and faintly alkaline. It was also converted into a
bydrochlorate. It gave the following reactions : —

Phosphomolybdic acid Gave a pale yellow white precipi-

tate.

Phosphotnngstic „ „ white precipitate.

Mercuric and potassium iodide ... „ pale yellowish white pre-

lodine solution
Tannic acid ...
Picric acid ...

cipitate.
brown precipitate.

Platinic chloride
Gold chloride

nil.

yellow,
nil.

slight yellow.

INDEX.

ABSORPTION of digestive
juices, 18, 39

of ptomaines from intes-
tines, 38, 41, 46

Accumulation of toxic products,
23

AcetonEemia, 57
Acetone, effects on blood, 57
Adenine from pancreas, 15, 16
Agarims muscarius, 8
Air of breath, noxious effects of,
26

Albuminous decomposition pro-
ducts of, 10

Alkaloid formation in the intes-
tines, 53

from human saliva, 18

from poisonous cheese, 40

poisonous in milk, ice cream,

and oysters, 6

meaning of, 1

separable from poisonous

fish, 6

Alkaloidal substances in urine,
92

Alkaloids, animal discovery of, 4
animal and vegetable simi-
lar, 7
biochemical, 14

— classified according to their
sources, 18

— due to bacterial life, 14

found in the urine, 54

from batrachians, fishes and

molusca, 18

from blood and viscera, 18

from breath, 18

from intestines, 18

from snake venom, 18

from spleen, 18

from thymus or testicle, 18

from urine, 18

Alkaloids identical with some

ptomaines, 7
increase in urine in typhoid

fever, 14

in the blood, 54

putrefactive poisoning by 46,

Ammonia in breath of typhus and

other diseases, 34

products, formation of, 33

Ammoniacal compound, a source

of typhus, 31
Ansomia, ohlorotic, 53
Anffirobic life, characteristic of

bacterial ferments, 14
Animal alkaloids poisoning phe-
nomena, 37

clinical aspects, 18

pathological aspects, 18

practical aspects, 18

poisoning by, 19

matter (putrid) poisoning

from, 18
Antagonistic action of ptomaines,

19

Anthrax, its inoculability, 68

theories regarding mode of

death from, 80

Anthropotoxine, 18, 27

Amphicreatinine, 17

Armies, typhus of, 26

Ashes physiological, 21

Asiatic cholera, 78

Atropine as an antidote, 49

Atropine-like action of some pto-
maines, 49, 50

Autochthonous, evolution of dis-
ease, 57

Autogenetic toxic agent in blood,
20

Autoinfection, 19

from physical fatigue, 23-

resistance to, 22

108

Index.

BACILLARY pathology, 63
Bacillus anthracis, ploma'ines

produced from, 81
Bacteria generate poisons, 69

liquefy gelatine, 76

swarm in fish, 51

Bacterial affections widely dif-
fused, 64

■ invasion of the system, 65

methods, fallacies of, 69

Beef-tea, injurious properties of,
45

Bennett, molecular pathology of,
63

Bert's experiments, 67
Betaine in human urine, 13, 16
Betaines, 16

Blood, alkaloids circulating in,
54

ammoniacal in typhus, 32

and viscera furnishing alka-
loids, 18
Botulism of the Germans, 38, 60
Bouchard's observations, 92
Breath furnishing alkaloids, 18
Butyric acid, action of, 42

CADAVERINE, 9
Camps, typhus fever of, 26
Canons laid down by Dr. Koch,
72

to be fulfilled by a contagium

vivum, 73
Catheterisni, fever of, 92
Cellular doctrine of Virchow, 63
Cheese, poisoning by, 50
poisonous ptomaines from,

40

Chemistry, importance of its
methods, 98

Cblorotic anaemia, 53

Cholera-bacillus, isolation of poi-
sons from, 71, 79

Cholera nostras, 78

Choleraic dejections yielding a
base, 18

diarrhoea 59, 78

Choline, 49

Chromogenio micro-organisms,
87

Classification of micro-organ-
isms, 87

Clinical aspects of animal allca-
loids, 18

Coma, diabetic, 57

Kussmnul's, 57

Comma-bacillus yielding pto-
maines, 71, 79

Constipation, poisonous efi"ects
of, 53

Constitutional diseases, nature
of, 20

Contagmm vivum, canons to be
fulfilled by, 73

Corpses, human, yield poisons, 9

Cow-pox, 75

Crnsco-creatinine, 17

Cumulative action of " extrac-
tives," 26

Curare, 9

Cyanhydrio acid, 17

DEATH, mode of, in anthrax, 80
De Chaumont's method of esti-
mating urine constituents,
89

Destruction of toxic products, 23
Diabetic coma, 57
Diarrhoea in infants, 6
Differentiation of microbes, 72
Digestive juices, absorption of,
48

Diphtheria, 75, 83
Discoveries slowly elaborated,
101

Disease caused by parasitical in-
fluences, 63

essentially chemical, 86

zymotic, 86

Diseases, augmentation of, alka-
loids in urine of, 93

not "entities," 60

ELIMINATION of toxic pro-
ducts, 22

Enteric fever, 75, SO

ptomaines in relation

to, 50

Enzyme of liquefaction, 76
Erysipelas, 74
Bthylencdiamine, 9

Index.

109

Experiments of Onimus, 68
Extractive compouuds poisonous,
88

Extractives, 3, 9, 11

continuous formation of, 11

cumulative action of, 26

found in urine, 88, also

Appendix

poisoning by, 19

weight of, 91

FALLACIES whicli beset bac-
terial methods of study, 69

Fatigue-fever, pathology ofj 23

physiology of, 23

weak link in the process of,

25

Faeces and urine yield poisons,
12

human, poisonone activity

of, 12

Female, exceptional condition
after delivery, 55

Ferments, digestive, action of
liver on, 43

Fever of over-taxation, 25

of prostration, 25

of catheterism, 92

Finkler's bacillus, 78

Fish, poisoning by, 50

swarm with bacteria, 51

Fliigge's classification of micro-
organisms, 87

GADENINB, 9
Glanders, 74
Gonorrhoea, 74

Gradation and variation in

pathology, 60
Guanine, 16

HAKVEY'S discovery of the

circulation, 101
Health, 21

Humoral pathology, 61
Hydrophobia or rabies, 83

Hydrophobic virus, a chemical

one, 84
Hyperthermia, 19, 37, 60
Hypothermia, 60
Hypo-xantliine, 16

IMMUNITY conferred by pro-
tective inoculation, 85

Inadequacy of organic functions,
37

Indican in urine, 93

Indigestion a cause of depres-
sion, 41

Inoculability of anthrax, 68

Intestines furnishing alkaloids,
18

Intestinal products, poisons
from, 41

JAIL-FEVER, 29
Jaillard's conclusions, 67

KOCH'S canons, 72
Karnine, 13, 16
Kreatine in animal tissues, 13
Kreatinine, 17

in urines, 13

leucomaine group, 17

Kussmaul's coma, 57

LACTIC acid poisonous to
muscle and nerve, 27

Laplat's conclusions, 67

Leprosy, 74

Leucomaines, 1, 3, 14

formation in living cells, 10

poisonous characters of, 18

symptoms of poisoning by,

49

Life, its nature, 21
Liquefaction of gelatine by bac-
teria, 76

Liver prevents passage of pto-
maines, 39

action on digestive fer-
ments, 43

Lupus, 74

110

Index.

MACKEEEL, ^reen, 50

poisoning by, 50

i-ed, 50

white, 50

Malta fevpr, 74

Measles, 75

Meat poisoning, 77

"tainting" of, 48

Metabolism, measurement of, 25

Methyl-quanidine, 78

Microbes, bow they act, 64

in relation to generation of

poison?, 75

tlie makers of poisons, 85

the virus or ''infecting

stuff" of two or more dis-
eases, 66

Micro-organisms as causes of
disease, 64

as sole cause of some

diseases, 71

photography of, 100

Milk, poisonous nature of some,
40

• "tainting" of, 48

Molecular death precedes bac-
terial invasion, 65

■ pathology of Dr. Bennett,

63

Muscarine, 49

from poisonous fish, 8

its synthetic formation, 8

Muscular activity, waste pro-
ducts poisonous, 27
Mydaleine, 9, 52

NEURIDINB, 8
Neurine, 8, 49

Newton's discovery of laws of

gravitation, 101
Nicotine, 9

ONIMUS, his experiments, 68
Organic bases similar to vege-
table alkaloids,
Over-exertion, fever of, 23

PANUM'S experiments, 40
Parasitical influences causing
disease, 63

Palhogenic organisms, 87

ptomaines, identification,

97

Pathological aspects of animal

alkaloids, 18
Pathology Humoral, 61

of fatigue fever, 23

variation and gradation in,

60

Peptones, nature not yet known,
47

poisonous, 9

Peptotoxine, 10
Physiological ashes, 21
classification of micro-
organisms, 87
Physiology of fatigue, 23
Photography of micro-organisms,
100

Physostigma as a remedy, 51
Pneumonia, 75

Poisons extracted from urine and

faeces, 12

from food decomposition, 47

generation of by microbes,

75

isolated by cholera-baeilluB,

71,79

Poisoning by "extractives," 19

by meat, 77

by putrefactive alkaloids, 49

Poisonous products from bac-
terial growth, 19

ot digestion, 46

Practical aspects of the animal
alkaloids, 28

Products of digestion poisonous,
46

Prostration, fever of, 23
Proteid substances yield poisons,
48

Protective inoculation, 85
Pseudo-xanthine, 16
Ptomaines, 1, 3

absorption of, 38

difficulties of investigations,

98

excreted by urine, 38

found in tetanus, 82

from snake poison, 13

• in disease, 55

— influence of liver on, 39

in health, 55

in putrid meats, 38

Index.

Ill

Ptomaines, in relation to enteric
fever, 5(3, also Appendix

in tlie intestines, 38

more abundant in disease

than in health, 97

pathogenic, identification

of, 97

poisonous character of, 18

from cheese, 40

from milk, 40

• from tinned food, 40

produced from bacillus an-

thracis, 81
resulting from puerperal

fever, 82
symptoms of poisoning by,

49

yielded by comma-bacillus,

71, 79
Putrescine, 7

Putrefying meats contain pto-
maines, 38

Putrid matter, chemical nature
of poison of, 5

Pnerperium, thrombosis in the,
55

Puerperal fever, production of

ptomaines in, 82
Pyridic compounds, 16

QALI, 1

RABIES, 83
Relapsing fever, 74
Removal of waste products, pro
visions for, 27, 35

SALIVA (human) yields an al-
kaloid, 18

Salmon, pickled, ptomaines from
40

tinned, ptomaines from, 40

Sarkine, 16

Sausages, poisoning by, 5, 50
Scientific raissionB, failure of, 99

Scoria, 21

Self-intoxication in disease, 53

Sepsin of Bergmann, 6, 9
Septiccemia, 74
Septine of Richardson, 5
Septinous fluids, virulence of, 68
Sheep-pox, 75

Snake poison yields ptomaines,
S'pasmotoxine, 83
Spleen furnishing alkaloids, 18
StercoraBmia, 13

Sulphuretted hydrogen, action
of, 42

Symptoms of poisoning from

putrid animal matter, 18
classification of, 19

TASTE, bitter due to an alka-
loid, 10

Tainted meat, symptoms from,
59

" Tainting " of meat and milk,
48

Tetanine, 82
Tetanatoxine, 82

Tetanus yielding four ptomaines,
82

Thrombosis in the puerperium,
55

Thymus; or testicle furnishing

alkaloids, 18
Toxaemia urinary, symptoms of,

94

Toxic products, accumulation of,
23

elimination of, 22

their destruction by

oxygenation, 22

urine, 92

Tuberculosis, 74

Typhoid fever, increase of alka-
loids in urine, 14, also Ap-
pendix

Typhotoxin, 35, 56, 70

Typhusation, 27

Typhus ammoniacal blood in, 32
connection between it and

dysentery, 31

de novo orgin of, 28

of armies, 26

fever, spontaneous origin of,

30

Tyrotoxican, 6, 50

112

Index.

UNCLASSIFIED group of leu-

iiiainos, 18
Uric acid, natural formation, 11
syntlietio formation,

11

• — - leucomaines, 16
Uride from urine, 18
Urine, alkaloids found in, 54

and fsEcea yield poisons, 12

constituents, estimation of,

89

poisoning, 92

toxic, 92

Uriuary toxaemia, 94

VACCINIA, 75

Variation and gradation in patho-
logy, 60
Variola, 75

Vegetable alkaloids similar to

animal, 7
Yibrio proteus, 78
Virchow, cellular doctrines of,

63

"Virulence Df septinous fluids, 68
Vital mechanism proteotive, 22

WALKING exercise, effects of,
25

Waste products, accumulation of,
23

remoTal of, 35

Wooldridge's experiments, 81

XANTHINE, 16

Xyantho-Creatinine, 17

X, y, z's, of morbid anatomy, 88

YEAST, decomposition of, yields
a poison, 6

ZYMOTIC diseases, 87

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