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' AND BOOKS

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WORKS NOT INCLUDED IN THESE
VOLUMES

Physiology of Man — Five Volumes of
about 500 pages each, 1866-1874. Second
Edition, 1875. Volumes IV and V are out
of print.

Manual of Chemical Examination
OF THE Urine in Disease, pp. 76, 1870.
Sixth Edition, 1884.

Text -Book of Human Physiology,
pp. 978, 187 1. Fourth Edition, 1888.

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i/frnton (T^^iJidr

COLLECTED ESSAYS
AND ARTICLES ON
PHYSIOLOGY AND MEDICINE

BY

AUSTIN FLINT. MD.. LL. D.

PROFESSOR OF PHYSIOLOGY IX THE CORNELL UNIVERSITY MEDICAL COLLEGE ; COXSULTIXG
PHYSICIAN- TO BELLEVfE HOSPITAL ; CONSILTING PHYSICIAN TO THE JIANHATTAN STATE
HOSPITAL FOR THE INSANE ANT) PRESIDENT OF THE CONSULTING BOARD ; MEMBER OF THE
A-MERICAN MEDICAL ASSOCIATION" : FELLOW OF THE NEW YORK STATE MEDICAL ASSOCIA-
TION ; MEMBER OF THE NEW YORK COUNTY MEDICAL ASSOCIATION ; MEMBER OF THE
MEDICAL ASSOCIATION OF THE GREATER CITY OF NEW YORK ; HONORARY MEMBER OF
THE AMERICAN ACADEMY OF MEDICINE ; MEMBER OF THE AMERICAN MEDICO-PSYCHO-
LOGICAL ASSOCIATION ; MEMBER OF THE AMERICAN PHILOSOPHICAL SOCIETY ; HON-
ORARY MEMBER OF THE ASSOCIATION OF MILITARY SURGEONS OF THE U. S. ; COR-
RESPONDEINT OF THE ACADEMY OF NATURAL SCIENCES. PHILADELPHIA; FEL-
LOW OF THE AMERia\N ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE ;
MEMBER OF THE AMERICAN ANTHROPOLOGICAL ASSOCIATION ; MEMBER OF
THE AMERICAN ACADEMY OF POLITICAL AND SOCIAL SCIENCE ; MEMBER
OF THE EXECUTIVE CO^LMITTEE OF THE NEW YORK PRISON ASSOCIA-
TION ; DECORATION OF THE THIRD CLASS, ORDER OF THE BUST
OF THE LIBERATi>R (B0LIVAR\ REPUBLIC OF VEN"EZUELA, ETC.

EDITOR OF THE BUFFALO MEDICAL JOURNAL, iSfS-'fo ; VISITING SITSGEON TO THE BUFFALO

GENERAL HOSPITAL, lS58-"53 ; MEMBER OF THE ERIE CdU"NTY" MEDICAL SOCIETT, iSjS-'sg ;

PR.-FESSOR OF PHYSI 'L'lGY IN THE MEDICAL DEPARTMENT OF THE UNIVERSITY OF BUFFALO,

i858-'5i) ; prl>fess<ir of physi >l iqy in the new Y'>rk medical C'Llege, i85o-"6o;

PROFESSOR of PHYSIOLOGY IN THE NE^V ORLEANS SCHOOL OF MEDICINE, l86o-I6l ;
ONE OF THE FOUNDERS AND PR 'FESSOR OF PHYSIOLOGY IN THE BELLEVUE HOSPITAL
MEDICAL COLLEGE, l86l-"p8 ; PROFESSOR OF PHi-SIOLOGY IN THE LONG ISLAND
C< 'LLEGE HOSPITAL, l862-'63 ; ACTING ASSISTANT SURGE'N, U. S. A., U. S. GENERAL
HOSPITAL, CITY op NEW V RK. lS52-'65 I CONSULTING PHYSICLVN TO THE CLASS
OF NERVOUS DISEASES, BELLEVUE HOSPITAL DISPENSARY, l866-'74 AND 1887-
'q6 ; VISITING PHYSICIAN TO BELLEVUE HOSPITAL, lS6o-'74 AND iSSj-'oP ;
SU"RGE N-GENERAL, STATE OF NEW YORK, lS74-'78 '. EXAMINING PHY-
SICIAN, CONNECTICIT MUTUAL LIFE INSURANCE COMPANY. NEW YORK
OFFICE, i87I-'8d ; PRESIDENT <'F THE NEW YORK STATE MEDICAL
ASSOCIATION, 1805 ; VISITING PHYSICIAN Ti'' THE INSANE PAVILION,
BELLEVUE HOSPITAL, lSa6-"o7 ; PRESIDENT OF THE JIEDIOVL
ASSOCIATION OF THE GREATER CITY OF N"EW YORK, 18Q9.

N'OLL'ME FIRST

NEW YORK
D. AP PL ETON AND COMPANY

Copyright, 1903
By AUSTIN FLINT

QTG

PREFACE

After nearly a half-centiiry of somewhat active and
varied literary work, I have collected and printed what is
contained in these two volumes, as an offering to those to
whom I am bound by ties of relationship or friendship. In
effect, I have omitted no article that has been published
under my name, however much it may have seemed to me
out of place in a collection made up chiefly of serious es-
says on professional topics. This collection begins, indeed,
with a paper written in 1855, and it includes a few articles
published in a periodical for young people. It contains,
therefore, everything I have written for publication and
signed, with the exception of one signed review, one or
two biographical memoirs and a very few short articles
relating to professional controversies which happily have
long since disappeared. It does not include, however, the
" Physiology of Man," in five volumes, " Text-Book of
Human Physiology " and " Manual of Chemical Exami-
nation of the Urine in Disease."

I trust that it may not appear to those for whom
these volumes are intended, that it would have been bet-
ter if I had deferred their publication and left it to be
done by others, if at all. With no intention or desire to
deprecate criticism, I simply say that they could not have
appeared in their present form unless the collection, ar-
rangement and revision had been made by myself; and I
feel that the burden of publication should be borne by
me and not left as a legacy.

iv PREFACE

I have revised all the articles very carefully, but not
more freely than is frequently clone in the correction of
first proofs. While I have eliminated some verbal redun-
dancies and attempted to correct what seemed to me no-
ticeable inelegancies of expression, especially in the earlier
writings, I have not changed the sense of any one article,
paragraph or sentence. It is proper that I should make
this statement for the reason that in a short analysis of
some of the articles, which is to follow, there will be in-
volved questions of priority of experiment, observation
and publication.

It was my intention to arrange the articles chrono-
logically; but I have deviated from this order in putting
together those on purely physiological and medical sub-
jects, following them with the miscellaneous writings. I
have also grouped a few articles on similar topics, espe-
cially when they represented series of experiments or ob-
servations. In some few instances there have been partial
repetitions, the same facts or arguments being used in
different relations. With these exceptions the chrono-
logical order has been preserved; and the date and place
of publication have been given in every instance, so that
a claim of priority of publication may be verified by any
one interested sufficiently to refer to the original.

The text-books on physiology of fifty years ago were
not often the work of practical physiologists; and in at-
tempts to present fairly the best opinions on the questions
considered, not infrequently opposite views of observers
were given, leaving to the reader the responsibility of
selection. It was seldom, indeed, especially in works pub-
lished in the English language, that matters in doubt or
dispute were discussed by authors practically familiar with
methods of physiological experimentation.

In 1857, the date of publication of the article on " Phe-
nomena of the Capillary Circulation," there were writers

PREFACE V

of authority who taught that the blood moved in the
capillary vessels in obedience to what was called the
" capillary power," an attractive force exerted by the tis-
sues on the nutritive constituents of the circulating fluid.
In my inaugural thesis (1857) I attempted to describe the
varied phenomena observed in studying the capillary cir-
culation under the microscope. In the course of these
observations I was fortunate enough to hit upon a method
of suppressing cutaneous respiration in the frog by cover-
ing the surface with a coating of collodion, which enabled
me to study the immediate effects of asphyxia on the capil-
lary circulation by direct examination. These were the
first microscopical observations of the arrest of capillary
circulation following suppression of the respiratory func-
tion; and they seem to me to be important even now, as
showing that blood deficient in oxygen can not circulate
freely in the capillaries, the obstruction being in the sys-
temic vessels and not in the lungs. While the demon-
stration was original, the theory was not new. Dr. John
Reid, of Edinburgh, advanced the same view in 1841. He
showed that the arterial blood-pressure in an asphyxiated
dog was much increased, while the pressure in a corre-
sponding vein was proportionally diminished as the as-
phyxia proceeded to the stage of insensibihty.

In 1 861 I made a number of experiments on the roots
of the spinal nerves and confirmed the observations of
Magendie, made in 1839, in which it was shown that the
anterior roots possessed a slight sensibility derived from
recurrent fibres from the posterior roots, concerning
which there had been differences of opinion. These were
the first observations of the kind made in this country.

In 1868 I had an opportunity of examining what pur-
ported to be an exact reprint of the celebrated " Idea of
a New Anatomv of the Brain," bv Sir Charles Bell, the

vi PREFACE

then reputed discoverer of the distinct properties and
functions of the two roots of the spinal nerves. This
pamphlet was, printed for private distribution only and
w^as practically inaccessible. I published in that year an
extended review of the claims of Bell and of Map^endie to
this important discovery and corrected an error almost
universal in the literature, including, even, the works of
French authors, attributing the discovery to Bell. I make
mention here of this publication for the reason that it led
writers generally, for the first time, to do justice to the
claims of Magendie. The article was followed by a re-
publication of Sir Charles Bell's pamphlet in the '' Journal
of Physiology," in 1869; and I had the satisfaction of see-
ing that the reprint W'hich I had used was accurate and
that my conclusions were justified.

In the articles on the action of the heart and on respi-
ration, published in 1861, 1874, 1877 and 1880, are records
of experiments which justify a claim of priority in the
description and explanation of certain phenomena ob-
served later by others and now universally adopted by
writers on physiology. I had an opportunity, while teach-
ing physiology in the New Orleans School of Medicine,
in i860 and 1861, to experiment on alligators of large
size. It is well known that the excised heart of cold-
blooded animals will continue to beat for a considerable
time. I demonstrated that the heart, when filled with
blood, the valves between the cavities having been cut
away, wilj beat powerfully and w'ith regular rhythm; w^hile
the pulsations are more rapid, feeble and irregular w^hen
the cavities are empty. I also showed that the pulsations
are relatively rapid and feeble when the cavities are filled
with water instead of blood. I made an application of
the phenomena observed to the rapid and feeble action
of the heart in the reaction from hemorrhage and in ane-
mia. The recent " perfusion experiments," made chiefly

PREFACE

vu

on the heart of the frog, are to a certain extent elabora-
tions of these observations. Systematic perfusion experi-
ments are said to have been begun by Merunowicz, in
Ludwig's laboratory, in 1875. They were repeated, with
improved methods, by Cyon and the phenomena observed
are now- the subject of extended investigation.

In this series of experiments I showed that while cu-
rara usually paralyzes the inhibitory nerves of the heart,
as well as the general motor system, in alligators these
nerves are not affected by the poison. Bernard had shown
this to be the case in birds. In addition to the observa-
tions on alligators I showed that in dogs enfeebled by
loss of blood inhibition of the heart is but slightly affected
by curara. I reasoned from this that these nerves are
" protected from disturbing influences, like the action of
poisons, to a greater degree than others."

The experiments on respiration, published in 1861, led
me to think that the " respiratory sense " had its origin
in the general system and was due to want of oxygen. I
expressed the same opinion in an address on the " ^lech-
anism of Reflex Nervous Action in Normal Respiration,"
published in 1874.

In 1877, when I extended my observations on the
" respiratory sense," or the starting point of the impulses
which give rise to the movements of inspiration, opinions
as to the action of the respiratory centre in the bulb were
varied and conflicting. Rosenthal (1862) and Pfliiger
(1868), subsequently to my experiments of 1861, had
shown that the respiratory sense was due to a general
deficiency of oxygen in the system, having noted dyspnea
in animals made to breathe pure nitrogen or hydrogen.
Kussmaul and Tenner (before 1858), having noted dys-
pnea after ligation of the carotids, extended previous ob-
servations and referred the convulsions observed in suffo-
cation and after profuse hemorrhage to a deficiency in
oxygen in the brain and in the bulb. They described the

viii PREFACE

so-called "convulsions of anemia"; and some physiolo-
gists assumed the existence of a " convulsion-centre " in
the bulb. As early as 1839 John Reid wrote that the
respiratory movements were due to the action of black
blood in the bulb. In 1841 Volkmann attributed the re-
spiratory movements to the stimulation of carbonic acid
in every part of the body. Direct and conclusive experi-
ments, however, showing the efifects of cutting off the
blood-supply from the brain and bulb,- contrasted with
those observed after cutting ofT the supply from the trunk
and lower extremities, were wanting. In my experiments,
first published in 1877, and discussed fully, with a review
of the literature, in an article entitled " Is the Action of
the Medulla Oblongata in Normal Respiration Reflex? "
published in 1880, I showed that after arresting the respira-
tory movements in animals by supplying air in abundance
to the lungs in artificial respiration, respiratory efforts
began, although artificial respiration was continued, when
the vessels given ofif from the arch of the aorta were
tied; and that no respiratory efforts were made when the
aorta was tied below the arch and arterial blood was al-
lowed to circulate in the head and anterior extremities.
I believe these to be the first experiments demonstrating
positively the effects of depriving the respiratory centre
of oxygen. The views resulting from these observations
are now universally accepted.

Eighteen hundred and sixty-two is the date of the pub-
lication of what appears in these volumes as Article IX.,
on a " New Excretory Function of the Liver." This arti-
cle was published in French in 1868. In 1869 it received
an "honorable mention" with a "recompense" of 1,500
francs from the Institute of France (Academic des Sci-
ences), Concours Monthyon (medecine et chirurgie), be-
ing second to the essay by Villemin, on the specific char-
acter and inoculabihty of tuberculosis, the most important

i

PREFACE ix

work in medicine since the discovery of vaccination, which
received the Monthyon prize for that year. In 1876 I
gave an abstract of my work in an address before the
International Medical Congress held in Philadelphia. An-
other abstract, with a review of the literature since 1862,
appeared in the " New York Medical Journal," in 1877.

I mention all of these publications in this place, for
the reason that in 1896 an article appeared in Hoppe-
Seyler's " Zeitschrift," in which most of my experiments
and physiological deductions were published as original
by two workers in Schroeder's Pharmacological Institute
in Heidelberg.

In my article of 1862 I described a new substance ex-
tracted from normal feces, which I called stercorin. I
showed that this substance was excrementitious and that
it resulted from a change of the cholesterin of the bile in
its passage through the small intestine, incident to the
process of intestinal digestion; that cholesterin was prob-
ably a catabolic product of nerve-tissue; that in certain
extensive structural diseases of the liver, the proportion
of cholesterin in the blood was largely increased, consti-
tuting a condition which I called cholesteremia; and that
this might account for theretofore unexplained grave
nervous symptoms.

The chemists who claimed to have discovered a new
substance in the feces called it " koprosterin." They ob-
tained it by practically the same process employed by me
for the extraction of stercorin, in 1862. The only varia-
tions which saved their method from being identical with
the process employed by me were the use of Soxhlet's
extraction-apparatus, not known in 1862, by which the
ethereal extracts were made more rapidly, and the re-
moval of fats by saponification with sodium alcoholate
instead of potassium hydrate.

In 1897, in the Address on Medicine at the semicen-
tennial anniversary of the American Medical Association,

X PREFACE

I gave an account of new experiments in which I extracted
stercorin by my original process and by this process as
modified in 1896. I also compared the two products with
a specimen of stercorin extracted in 1862, w'hich I had
fortunately preserved, verifying the empiric formula for
each. I found the three products to be identical as to
formula, reactions and form of crystals.

Later in 1897 I sent these facts to Hoppe-Seyler's
" Zeitschrift," w'ith a reclamation of priority, which were
published in German in August of the same year. The
discoverers of " koprosterin " denied my claim of the iden-
tity of their product with stercorin, basing this denial on
a statement made by me in 1862, that stercorin fused at 36°
C. " Koprosterin " fuses at 95°-96°. In 1862 I regarded
stercorin as probably identical with a substance which had
been extracted in minute quantity from the serum of the
blood, by Boudet, called seroline; and I quoted Lehmann
as giving 36° as its fusing point. I do not remember,
after an interval of forty years, that I attempted to take
the fusing point of the stercorin which I obtained from
feces.

In this brief analysis I have simply recited facts which
I trust some may take the trouble to verify by referring
to the articles themselves; and I have no desire to add
what can be regarded as in any degree polemic. Assum-
ing a familiarity on the part of the chemists referred to
with the literature — which was not denied — I venture only
to suggest, as a possible reason why the pathological as
well as the physiological ideas as to the relations of ster-
corin were not appropriated, that W'Orkers in pure chem-
istry can hardly be expected to appreciate the importance
of such researches in their applications to practical medi-
cine.

At the time the article " On the Organic Nitrogenous
Principles of the Body with a New Method for their Esti-

PREFACE xi

mation in the Blood " was published (1863), all the anal-
yses of the blood to be found in works on physiology
gave estimates of dried albumin, fibrin and corpuscles.
The " new method " described in this article refers chiefly
to estimates of albumin and fibrin. Physiological chem-
ists, among whom may be mentioned Dumas, Denis,
Figuier, Becquerel and Rodier, Schmidt, and Zimmer-
mann, had attempted to estimate the corpuscles in their
moist, or natural condition. In my analyses for organic
nitrogenous matters I obtained the proportions of moist
albumin and fibrin; but physiologists now recognize, in-
stead of albumin and fibrin, a number of proteids in the
blood-plasma that had not been described in 1863. I suc-
ceeded, employing a method adapted from Figuier, in
estimating, with fair accuracy, the corpuscles in their nor-
mal condition. ]\Iany attempts to do this had been made,
by processes very complex and uncertain. Nearly all
works on physiology now give the proportion of moist
corpuscles, which closely corresponds with my estimates;
and the method which I employed was so simple and easy
of application that it could be made use of in hospital
or private practice. Of late years, however, apparatus
for blood-counting has superseded chemical analysis in
clinical work.

The remarkable discovery by Bernard, published in
1848, of what he called the sugar-producing function of
the liver was received with much enthusiasm; and his re-
markable experiments were extensively repeated and fre-
quently used as demonstrations in the teaching of physiol-
ogy. A few years later, Pavy claimed to have demon-
strated that neither the liver nor the blood of the veins
between the liver and the heart contains sugar during
life; and that the sugar found by Bernard in the liver and
in the blood of the hepatic veins was the result of post-
mortem changfe of an amvloid substance. This latter view

xii PREFACE

found main- adherents, parlicidaily in JuiL;land and Ger-
many; so that in \H(h) tlie (|iiestion was unsettled.

In 1869 1 puhHshed an aecount of experiments " un-
dertaken for the purpose of reconeihng- some of the dis-
cordant observations on the glycogenic function of the
liver." These experiments, so far as i know, were the
first made with this object. In 1857 the description by
Bernard of a substance in the liver, called glycogen, which
is gradually changed into sugar by a ferment and is car-
ried away as sugar by the liepatic veins, seemed to com-
plete the discovery of the glycogenic function. In my
experiments I attempted the analysis of the substance of
the liver in a condition as nearly as possible approaching
that of the organ actually in the living body. I opened
the abdomen rapidly and cnt a portion of the liver, pre-
viously rinsed in w^arm w'ater, into boiling water, the oper-
ation lasting but ten seconds. I found no sugar in the
liver, but the blood of the hepatic veins, taken from the
same dog, contained sugar. From these experiments I
concluded that during life the liver contains no sugar, thus
verifying the results obtained by Pavy; but that sugar
resulting from a transformation of glycogen, as fast as it
is formed, is w'ashed out by the blood-current and appears
in the blood of the hepatic veins, thus confirming the re-
sults obtained by Bernard. My experiments seemed to
harmonize the apparently discordant observations of these
tW'O physiologists. Since that time it has been the gen-
erally received opinion that the liver stores up the prod-
ucts of digestion of the carbohydrates in the form of gly-
cogen, and, in the carnivora at least, produces glycogen,
probably from the proteids; and that glycogen is gradu-
ally changed into sugar wdiich is carried away in the
blood of the hepatic veins, where it always exists during
life. In the experiments recorded in this article portions
of the liver were taken from living animals and analyzed
for sugar much more rapidly than in any previous ob-

PREFACE xiii

servations with which I am acquainted. These experi-
ments were repeated and somewhat extended by Lusk
in 1870.

The ideas in regard to the storing up of the carbo-
hydrates of food in the hver in the form of glycogen and
their gradual discharge into the blood in the form of sugar,
which these and other observations led me to entertain,
prompted me to make studies of the relations of diet to
diabetes mellitus, the results of which appear in Articles
XV., XVI. and XVII., published in 1884 and 1887.

In 1870 my interest in physical training and athletics
led me to witness the close of an effort by a professional
pedestrian to walk a hundred miles in twenty-two con-
secutive hours. By a mere chance I was able to procure
all the urine said to have been passed during that period.
The attempted feat of endurance was accomplished; and
my examination of the urine seemed to show that the un-
usual muscular effort largely increased the elimination of
nitrogen by the kidneys. This result encouraged me to
make an attempt to settle the disputed question of the
influence of muscular work on the elimination of nitrogen,
by a carefully prepared and much more elaborate series
of investigations on the same person in an attempt to
walk four hundred miles in five consecutive days. The
details of these observations, made in the fall of 1870, are
embodied in Articles XVIII., XIX. and XX. The results
were definite and, as it seemed to me, conclusive. I com-
pared the outgo with the income of nitrogen for three
periods of five days each, including the five days of the
walk.

The most important of the conclusions related to the
elimination of nitrogen and its proportion to the nitrogen
of the food. For the five days of the walk, I found 154
parts of nitrogen discharged for every 100 parts of nitro-
gen of food, against 93 parts, for the five days before the

xiv PREFACE

Avalk, and 85 parts, for the five days after the walk. The
investigations which formed the basis of these articles in-
volved much labor, and they are by far the most extensive
ever made on the questions considered. However, in 1876
a similar series of observations was made by Dr. Pavy, of
London, upon the same person, in a walk of six consecu-
tive days. The general results of these experiments con-
firmed my ow^n, obtained in 1870; although my conclu-
sions were not accepted, on theoretical grounds.

A careful study of the observations by Dr. Pavy and
others led me to publish, in 1877, the essay entitled
" Source of ^Muscular Power," in which I embodied my
own investigations, made in 1870, the results of Dr. Pavy's
investigations, made in 1876, with a discussion of experi-
ments by other physiologists, made on a smaller scale.
Since this publication it has appeared that certain quoted
estimates — at the best of doubtful accuracy — used in my
calculations, probably were incorrect; but the possible er-
rors involved do not materially afTect the general conclu-
sions. Quoting from this essay:

" I feel that I am justified in claiming priority in the
method of investigating the influence of exercise upon the
excretion of nitrogen by comparing the nitrogen elim-
inated with the nitrogen of food."

As my experimental data seemed opposed to the views
of Pick and WisHcenus, w^iich were then quite generally
accepted, the observations and conclusions of Oppenheim,
made in 1880, are of interest. Oppenheim concludes that
muscular work, when not carried to the extent of pro-
ducing shortness of breath or when moderate and extend-
ing over a considerable length of time, does not increase
the elimination of nitrogen; but that even less work, when
violent and attended with shortness of breath, increases
the discharge of nitrogen. In other words, when the in-
creased elimination of carbon dioxide, due to muscular
work, has reached its limit, the additional work is repre-

PREFACE XV

sented by an increased elimination of nitrogen. An ac-
ceptance of this proposition would go far to harmonize
the results obtained by different experimenters.

Without further discussion I may say that recent ad-
vances in knowledge of the phenomena of nutrition and
catabolism do not seem to have impaired, in any impor-
tant degree, the value of my experiments and conclusions
made thirty-two years ago.

The researches which formed the basis of the articles
upon the influence of muscular work on the elimination
of nitrogen and the essay on the source of muscular power
naturally led to a study of animal heat and the applications
of the theories of calorification to fever and its rational
treatment. In discussing the source of muscular power
I made use of the estimate by Senator, of the probable
production of four heat-units per hour per pound of body-
weight; and the same estimate was adopted in the article,
" Experiments and Reflections on Animal Heat," pub-
lished in 1879. With this estimate — which I regarded as
not entirely reHable — it seemed impossible to account for
the heat thus assumed to be actually produced and either
used or lost by radiation, by the heat-value of food. Even
with the estimate, made by the indirect method, of two
and a half heat-units per pound per hour, it was difficult
to account for the heat produced, by the heat-value of
the processes usually regarded as involved m calorifica-
tion.

Assuming that the total heat produced in the body,
deducting the loss by heat-dissipation, is used to maintain
the animal temperature and to accomplish work, the ele-
ments in the problem of its expenditure are discouragingly
uncertain as regards estimates of the quantities converted
into force to maintain circulation and respiration and to
accomplish general muscular work. The most important
element in this problem, however, is the estimation of the
actual quantity of heat produced per pound of body-weight

xvi PREFACE

per hour; and a fairly accurate estimate of this would ren-
der calculations of the proportion lost, the proportion used
as force and to maintain the body temperature compara-
tively unimportant in ascertaining the sources of heat-
production and muscular power; assuming, as we must,
the validity of the law of the correlation and conservation
of forces. But with the lowest estimates of heat expended
as force, it is difficult, if not impossible to account for it
by the heat-value of food or tissue consumed, represented
by the excreta, assuming anything near accuracy in these
measurements. To solve the problem, even approxi-
mately, it is necessary to find sources of heat which will
much more than account for the work, reduced back
from force-units to heat-units, the maintenance of body-
heat and the loss by heat-dissipation.

The difficulties that I have indicated in a measure ac-
count for the indeffiiite, not to say obscure manner in
which the subject of animal heat and force is treated in
nearly all modern systematic treatises on physiology. In
general terms, it may be said that the indirect method of
estimating heat-production is to calculate the heat-value
of oxygen taken in and correct this by comparing it with
the heat-value represented by oxidized matters discharged.
This has been found to correspond fairly well with the cal-
culated heat-value of food. Such a calculation, however,
almost begs the question; it simply indicates what should
be the heat-production and assumes that the heat-pro-
duction is what the calculations show that it should be.
The strictly logical process is the direct method, using
the calorimeter, and measuring, if possible, the heat ac-
tually produced. By the indirect method, the calculated
heat-production about equals the calculated heat-value of
food, with the body in a condition of physiological equilib-
rium; but the food accounts for only about 62^ per cent,
of the heat actually produced, calculated by the direct
method. With the very large elements of uncertainty in

PREFACE xvii

the reduction of the force used in circulation and respira-
tion and in general muscular work to heat-units, the ques-
tion of heat and force-production in the body seems as
far from a satisfactory solution to-day as it was before
1879.

Although Lavoisier and Laplace, in 1780 and 1785,
had attributed heat-production to oxidation of carbon and
hydrogen, it had never been demonstrated, before my ex-
periments published in 1879, that oxygen actually unites
in the body with hydrogen to form water. The heat-value
of such oxidation is very great; and this, added to the
heat represented by the carbon dioxide, urea, etc., eHm-
inated, would much more than account for the heat ac-
tually produced and used either as heat or as force, making
the calculations of heat produced, either by the direct or
by the indirect method. The increase in the production
of water due to increased muscular work also would ac-
count for the necessary increase in the production of heat
to supply the force.

I think I was the first to demonstrate positively by
experiments, some of which were made on my own per-
son, that under conditions, at least, when oxidation repre-
sented by carbon dioxide and nitrogenous excretions is
not sufficient to supply the heat required, water is pro-
duced in the body, as is shown by a considerable excess
of water discharged over and above the water taken in,
without loss of water by the liquids and tissues of the or-
ganism. I could thus account, also, for the oxygen of the
respired air lost and not represented in carbon dioxide and
other excreta.

At the ninth session of the International Medical Con-
gress, held in Washington in 1887, addresses were made
in general session by representatives of Great Britain,
France, Austria, Germany, Italy and the United States.
I was honored with the appointment to deliver the ad-
dress in behalf of the United States; and I chose the sub-

xviii PREFACE

ject of " Fever." In this address I endeavored to apply
my studies in animal heat to the mechanism and rational
treatment of fever, especially in the way of supplying ma-
terial to feed the fever and save the tissues until the dis-
ease should have run its self-limited course, restricting,
also, the destruction and degenerations of tissue by re-
ducing temperature. I took the ground that in certain
cases it became necessary to " feed the fever " with al-
cohol.

There has been, is at the present time and probably
will be far into the future, violent and acrimonious dis-
cussion as to the fate of alcohol taken into the body. The
main question now agitated is whether or not alcohol,
taken in quantity not sufficient to produce intoxication,
is oxidized and serves as food or, if not directly as food,
as an agent restricting the waste of tissue. A controversy
between the laity, opposed on moral grounds to the use of
alcohol, and scientific observers not practically familiar
with disease and its treatment but relying on studies of the
changes which alcohol undergoes in the healthy organism,
is not likely to promote a scientific solution of the question
involved. While it may be that in a healthy person, ade-
quately nourished, alcohol is not useful, even if not ac-
tually harmful, and that it can not contribute, except mo-
mentarily, to mental or physical power and endurance,
in its judicious and careful therapeutic administration, in
many diseases, it is often of great value. I therefore ad-
here to the views embodied in the two articles on fever
and in the article " On Some of the Therapeutic Uses of
Alcohol," published in 1887.

It is calculated that 10 grains of absolute alcohol,
when oxidized, will produce 23 heat-units; and one
ounce, weighing about 384 grains, is equal to about
883 heat-units. In fever alcohol administered in certain
quantity is not eliminated as alcohol: it does not intoxi-
cate and, as it seems, it must be oxidized. Thus admin-

PREFACE

XIX

istered it does not increase pyrexia; and if oxidized, it
must save tissue and moderate degenerations. If these
statements are true, alcohol can not properly be eliminated
from therapeutics any more than morphin or strychnin.

While I have thought it well, for the benefit of those
who may be led to read some of the articles here repub-
lished, to give, in a brief analysis, a rather more extended
account of what is contained in these volumes than is to
be found in the Table of Contents, I have not intended
to refer to individual articles unless they presented some
claim to original investigation or to unusual methods of
treatment of the subjects considered. In the three articles
on examination of urine I insisted on the importance of
examinations in all cases of application for life insurance,
which was rarely done at the time I became a medical
examiner for a large company, in 1871. An experience
of fifteen years in such work confirmed me in this judg-
ment. I endeavored, also, to popularize in the profession
urinary examinations by the general practitioner, by pre-
senting rapid and easy methods sufficiently accurate for
ordinary clinical purposes.

In 1888 I reported a case, in Article XXXII., of sci-
atica treated, with very prompt relief, with doses of anti-
febrin much larger than ever used before.

I may also refer briefly to a " Tonic Formula " (Article
XXXIII. ), which has been largely used since the publica-
tion of this article in 1889. In calculating this formula
I endeavored to make a preparation containing the inor-
ganic constituents of the blood in about the normal pro-
portions, with an excess of iron and of sodium chloride,
to be used as a remedy in certain cases in which it seemed
to me that patients were suffering from deficiency in saline
matters as well as corpuscles. My own experience with

XX PREFACE

the " Saline and Chalybeate Tonic " has been quite satis-
factory; and I have lately seen an imitation of the formula
recommended for the purpose I have indicated.

The so-called " Frenchy " murder trial, in 1891, ex-
cited at the time great professional and popular interest,
on account of the peculiar atrocity of the crime, the sav-
age character and history of the accused and the very un-
usual nature of the expert testimony. The evidence in
this case was entirely circumstantial; and there is now
much difference of opinion in regard to the justice of the
verdict. This case was again brought to public notice by
the release of the prisoner after eleven years of confine-
ment under a life sentence for murder in the second de-
gree, part of the time in the Asylum for Insane Criminals.
The very last article of this collection gives a brief retro-
spect of the case, written on the occasion of the action
of the Governor of the State of New York.

The verdict of the jury rested practically on testimony
as to recognizable differences between the contents of the
small and of the large intestine, small portions of which
were found about the person of the victim and the person
of the accused, including matters taken from beneath the
finger nails. " The evidence which convicted the prisoner
was that the various specimens examined by the experts
for the people presented blood mixed with matters which
must have come from the small intestine, and which by
no reasonable theory, could be on the prisoner's clothing
and person unless they came from the body of the mur-
dered worrian. It is this point in the case which, so far
as I know, is without precedent and is of peculiar medico-
legal interest."

It is to be regretted that a full report of this case has
never been published and that my own testimony is all
that has appeared. So far as expert work is concerned,
the case is unique.

PREFACE xxi

Late in 1892 I began to use bismuth subgallate in so-
called functional dyspepsia attended with gastric and in-
testinal flatulence. I was led to the use of this remedy by
seeing it recommended for the diarrhea of children, acting
as a disinfectant. I think I was the first to administer it
in ordinary digestive disturbances. It is now very ex-
tensively prescribed, and the general experience in regard
to its value as an antifermentative is in accord with my
own.

The case of " Filaria " with chyluria (Article XXXVI.),
reported in 1895, is the first on record in which methylene
blue was employed with the view of destroying this re-
markable nocturnal parasite. I advised this remedy in the
•case reported, reasoning from my experience in its action
on the Plasmodium malarise. It w^as suggested in this
article that there was a " possibility of benefit from methy-
lene blue in the treatment of other diseases due to the
filaria, such as chylous collections in the peritoneal cavity
and in the cavity of the tunica vaginaHs testis, hematuria
and elephantiasis."

In 1867, at the request of the then Commissioners of
Public Charities and Correction of the City of New York,
I made an examination of the food supplies and methods
of cooking and serving in Bellevue Hospital and in the
other hospitals, prisons, etc., under their charge. This
resulted in the recommendation of the dietaries embodied
in Article XXXVII. It is almost unnecessary to say
that for many years, the sick poor, the pauper insane,
prisoners and others, including infants and children, under
the care of the City and State have been subject to the
vicissitudes of politics. They sutifer, on the one hand, from
the ignorance or indifference of administration, and on
the other, from w^ell-meant efforts of dietetists to reduce
nutritive supply to the calculated requirements of nitrogen

xxii PREFACE

and carbon. It is fair to say that the dietaries suggested
were for a time carried out as fully as possible under the
then existing methods of purchase of supplies and of ap-
pointment of subordinate officers; but the many, and some-
times revolutionary changes in administration, that have
occurred since 1867, have led to such modifications in
these dietaries that their original character has long since
disappeared. I take this opportunity, however, again to
express my confidence in dietaries constructed on physi-
ological rather than on purely chemical principles applied
to metabolism; a belief which I think is shared by physi-
cians familiar with disorders in general nutrition so often
seen in private practice as well as in hospitals, asylums
and prisons.

I also prepared dietaries for the State Hospitals for the
Insane, in 1893, the population of which considerably ex-
ceeded twenty thousand. These dietaries were placed on
trial for one year. They were then revised in accordance
with suggestions and recommendations made by the Su-
perintendents of the different hospitals. The revised re-
port is republished as Article XXXVIII.

In 1898 there was a change in the personnel of the
State Commission in Lunacy; and the dietaries in opera-
tion since 1894 were superseded on the ground of economy.
I can not question the wisdom of this change, for lack of
information in regard to the experience with the new
schedules; although very elaborate tables showing the cal-
culated nutritive requirements were published in 1899 and
1900, in which it appeared that these requirements could
be adequately met by the calculated nutritive values of
supplies less than those in use. Still another change oc-
curred, in December, 1900, when the President of the
Commission, appointed in 1898, was removed by the Gov-
ernor. The dietaries were again more or less modified
under the new administration; but I have little or no in-
formation as to the nature of these changes.

PREFACE xxiii

In 1895, at the request of the Comptroller of the State
of New York, I prepared schedules of diet for the various
State charitable and reformatory institutions reporting to
the Comptroller's Office. These were made on the same
general lines as those of the dietaries for the State hos-
pitals, but with certain modifications that are indicated
in Article XXXIX. These dietaries, however, were never
put into operation, and they are now published for the
first time.

I was appointed by the Governor of the State of New
York, in 1894, the medical member of a commission of
three to investigate the administration of the New York
State Reformatory at Elmira, in view- of certain charges
brought against the General Superintendent. I was the
joint author, with the Hon. Israel T. Deyo, of the major-
ity report of this commission, w'hich was adopted by the
Governor. This report is not republished in these volumes
for the reason that I was not its sole author; but I am
glad to have the opportunity of putting myself again on
record as approving the reformatory system, especially as
it was carried out at Elmira. Article LIX., on the " Sci-
entific Treatment of Crime and Criminals," and Article
LX., " The Pain of Death," embody most of the features
of this report that are of interest to the medical profession
and to criminologists.

I am also more than ready to go on record as opposed
to capital punishment. My view's on this question — one
of great importance to our social system — are contained
in the address on " The Pain of Death," before the " Quill
Club," made in 1897.

What I have just written completes the analysis of the
strictly scientific essays and articles. In addition to these
are twenty-one magazine articles, which have appeared
in various periodicals between 1866 and 1901, including

xxiv PREFACE

two (" Gymnastics " and " Pugilism ") published in the
"American Cyclopaedia," in 1874 and 1875. In these arti-
cles I attempted the difficult task of popularizing certain
scientific subjects. Many of the titles are not my own
but were suggested by editors. I do not feel competent
to decide whether or not my efforts to clothe scientific
questions in popular language and style have been suc-
cessful. Articles LIV., LV. and LVL, however, are more
serious than some of those classed as " Miscellaneous."
They were published in " The Forum " in 1888, 1889 and
1891 and are devoted mainly to bacteriology and its bear-
ing on the recent remarkable progress in medicine and
surgery. It is gratifying to see that many of the predic-
tions which I ventured to make at the time these articles
were written, when the bacterial theories of disease were
in their infancy, have since been realized. Studies in bac-
teriology, dating from the discovery of the tubercle ba-
cillus by Koch, in 1882, excited much popular as well as
scientific interest; and " The Forum " was one of the first
of the magazines devoted to general literature to publish
articles on this subject.

The rather formidable list following the name on the
title page would, perhaps, be out of place, except as repre-
senting a personal professional history in volumes which
include all my literary work up to the present date.

New York, November, igo2.

CONTENTS OF VOLUME FIRST

ESSAYS AND ARTICLES ON PHYSIOLOGY AND
MEDICINE

I

PAGE

AN ANALYSIS OF ONE HUNDRED AND SIX CASES OF

PARONYCHIA i

Published in the "Buffalo Medical Journal" for October, 1S55.

II

PHENOMENA OF THE CAPILLARY CIRCULATION— AN
INAUGURAL DISSERTATION LAID BEFORE THE FAC-
ULTY OF THE JEFFERSON MEDICAL COLLEGE IN

FEBRUARY, 1857 11

Published in the "American Journal of the Medical Sciences" for
July, 1857.

Ill

EXPERIMENTS ON THE RECURRENT SENSIBILITY OF

THE ANTERIOR ROOTS OF THE SPINAL NERVES . 29
Published in the "New Orleans Medical Times," in 1861.

IV

HISTORICAL CONSIDERATIONS CONCERNING THE PROP-
ERTIES OF THE ROOTS OF THE SPINAL NERVES . 35
Published in the " Quarterly Journal of Psychological Medicine " for
October, i863.

EXPERIMENTAL RESEARCHES ON POINTS CONNECTED
WITH THE ACTION OF THE HEART AND WITH

RESPIRATION 61

Published in the " American Journal of the Medical Sciences" for
October, 1861.

XXV

PAGE

xxvi CONTENTS OF VOLUME FIRST

VI

MECHANISM OF REFLEX NERVOUS ACTION IN NOR-
MAL RESPIRATION— AN ADDRESS DELIVERED FEB-
RUARY i6, 1874, BEFORE THE NEW YORK SOCIETY
OF NEUROLOGY AND ELECTROLOGY . . . .112
Published in the " Chicago Journal of Nervous and Mental
Diseases " for April, 1874.

VII

EXPERIMENTS ON THE EFFECTS UPON RESPIRATION
OF CUTTING OFF THE SUPPLY OF BLOOD FROM
THE BRAIN AND MEDULLA OBLONGATA . . .124
Published in the " New York Medical Journal" for November, 1877.

VIII

IS THE ACTION OF THE MEDULLA OBLONGATA IN

NORMAL RESPIRATION REFLEX? 136

Published in the " American Journal of the Medical Sciences " for
July, 1880.

IX

EXPERIMENTAL RESEARCHES INTO A NEW EXCRETORY
FUNCTION OF THE LIVER; CONSISTING IN THE RE-
MOVAL OF CHOLESTERIN FROM THE BLOOD, AND
ITS DISCHARGE FROM THE BODY IN THE FORM OF
STERCORIN. (THE SEROLINE OF BOUDET.) . . .163
Published in the " American Journal of the Medical Sciences" for
October, 1S62.

X

THE EXCRETORY FUNCTION OF THE LIVER . . .239

Published in the " Transactions of the International Medical

Congress," held in Philadelphia in September, 1876.

XI

STERCORIN AND CHOLESTEREMIA 258

Published in the " New York Medical Journal " for June 5, 1897.

XII
UEBER STERCORIN 272

Published in Hoppe-Seyler's " Zeitschrift fiir physiologische
Chemie," August 28, 1897.

CONTENTS OF VOLUME FIRST xxvii

XIII

PAGE

ON THE ORGANIC NITROGENOUS PRINCIPLES OF THE
BODY WITH A NEW METHOD FOR THEIR ESTIMA-
TION IN THE BLOOD 277

Published in the " American Journal of the Medical Sciences" for
October, 1863.

XIV

EXPERIMENTS UNDERTAKEN FOR THE PURPOSE OF
RECONCILING SOME OF THE DISCORDANT OBSERVA-
TIONS ON THE GLYCOGENIC FUNCTION OF THE
LIVER 315

Published in the " New York Medical Journal" for November,
i86q.

XV

THE TREATMENT OF DIABETES MELLITUS . . .323

Published in the "Journal of the American Medical Association"
for July 12, 1884.

XVI

FOUR SELECTED TYPICAL CASES OF DIABETES MEL-
LITUS NOT BEFORE REPORTED 349

Published in the " New York Medical Journal " for November 22,

1884.

XVII

LITHIUM CARBONATE AND SODIUM ARSENATE DIS-
SOLVED IN CARBONIC ACID WATER IN THE TREAT-
MENT OF DIABETES MELLITUS 356

Published in the " Medical News" for July 9, 1887.

XVIII

THE INFLUENCE OF EXCESSIVE AND PROLONGED MUS-
CULAR EXERCISE ON THE ELIMINATION OF EF-
FETE MATTERS BY THE KIDNEYS 366

Published in the " New York Medical Journal " for October, 1870.

PAGE

xxvi CONTENTS OF VOLUME FIRST

VI

MECHANISM OF REFLEX NERVOUS ACTION IN NOR-
MAL RESPIRATION— AN ADDRESS DELIVERED FEB-
RUARY i6, 1S74, BEFORE THE NEW YORK SOCIETY
OF NEUROLOGY AND ELECTROLOGY .... 112
Published in the " Chicago Journal of Nervous and Mental
Diseases " for April, 1874.

VII

EXPERIMENTS ON THE EFFECTS UPON RESPIRATION
OF CUTTING OFF THE SUPPLY OF BLOOD FROM
THE BRAIN AND MEDULLA OBLONGATA . . .12+
Published in the " New York Medical Journal" for November, 1877.

VIII

IS THE ACTION OF THE MEDULLA OBLONGATA IN

NORMAL RESPIRATION REFLEX? 136

Published in the " American Journal of the Medical Sciences " for
July, 1880.

IX

EXPERIMENTAL RESEARCHES INTO A NEW EXCRETORY
FUNCTION OF THE LIVER; CONSISTING IN THE RE-
MOVAL OF CHOLESTERIN FROM THE BLOOD, AND
ITS DISCHARGE FROM THE BODY IN THE FORM OF
STERCORIN. (THE SEROLINE OF BOUDET.) . . .163
Published in the " American Journal of the Medical Sciences" for
October, 1862.

X

THE EXCRETORY FUNCTION OF THE LIVER . . .239

Published in the " Transactions of the International Medical

Congress," held in Philadelphia in September, 1876.

XI

STERCORIN AND CHOLESTEREMIA 258

Published in the " New York Medical Journal " for June 5, 1897.

XII
UEBER STERCORIN 272

Published in Hoppe-Seyler's " Zeitschrift fur physiologische
Chemie," August 28, 1897.

CONTENTS OF VOLUME FIRST

XIII

PAGE

ON THE ORGANIC NITROGENOUS PRINCIPLES OF THE
BODY WITH A NEW METHOD FOR THEIR ESTIMA-
TION IN THE BLOOD 277

Published in the " American Journal of the Medical Sciences" for
October, 1S63.

XIV

EXPERIMENTS UNDERTAKEN FOR THE PURPOSE OF
RECONCILING SOME OF THE DISCORDANT OBSERVA-
TIONS ON THE GLYCOGENIC FUNCTION OF THE
LIVER 315

Published in the " New York Medical Journal " for November,
1869.

XV

THE TREATMENT OF DIABETES MELLITUS . . .323

Published in the "Journal of the American Medical Association"
for July 12, 1884.

XVI

FOUR SELECTED TYPICAL CASES OF DIABETES MEL-
LITUS NOT BEFORE REPORTED 349

Published in the "New York Medical Journal " for November 22,

18S4.

XVII

LITHIUM CARBONATE AND SODIUM ARSENATE DIS-
SOLVED IN CARBONIC ACID WATER IN THE TREAT-
MENT OF DIABETES MELLITUS 356

Published in the " Medical News" for July 9, 1887.

XVIII

THE INFLUENCE OF EXCESSIVE AND PROLONGED MUS-
CULAR EXERCISE ON THE ELIMINATION OF EF-
FETE MATTERS BY THE KIDNEYS 366

Published in the " New York Medical Journal " for October, 1870.

xxviii CONTENTS OF VOLUME FIRST

XIX

PAGE

ON THE EFFECTS OF SEVERE AND PROTRACTED MUS-
CULAR EXERCISE; WITH SPECIAL REFERENCE TO
ITS INFLUENCE ON THE EXCRETION OF NITROGEN 375
Published in the " New York Medical Journal" for June, 1871.

XX

SUPPLEMENTARY REMARKS ON "THE EFFECTS OF SE-
VERE AND PROTRACTED MUSCULAR EXERCISE;
WITH SPECIAL REFERENCE TO ITS INFLUENCE ON

THE EXCRETION OF NITROGEN" 461

Published in the " Journal of Anatomy and Physiology," Cambridge
and London, for October, 1876.

I

AN ANALYSIS OF ONE HUNDRED AND SIX
CASES OF PARONYCHIA

Published in the " Buffalo Medical Journal " for October, 1855.
PARONYCHIA BENIGNA

The private records of Dr. F. H. Hamilton contain
■eighty-one cases of paronychia benigna.

In all these cases the sex has been noted, and the pro-
portion of females to males is nearly two to one, there being
fifty-three females and twenty-eight males. In considering
the occupation of these patients and, as far as could be as-
certained, the causes which operated to produce the dis-
ease, in the great majority of cases it was found that the
•occupation involved manual labor; and where the occupa-
tion was noted as the cause of the disease, it was most fre-
quently an occupation in which females are generally en-
g'aged. In the male patients, the cause w^as generally a
bruise or slight injury to one of the fingers and not the oc-
cupation. As feminine duties frequently cause paronychia
and accidental injuries are the most frequeftt causes in the
male subject, it is not surprising to find a larger proportion
■of cases occurring in females.

In sixty-one cases the hand affected with the parony-
chia was designated.

Of these cases forty-two occurred on the right hand
and nineteen on the left; showing that the right hand,
being more used and more subject to accidental injuries,
is much more liable to this affection.

In seventy-five cases the diseased finger was designated.
The thumb and first finger, which are most used, were
affected in the greatest proportion of cases and appeared
to be about equally liable to the disease. The thumb was
the seat of the affection in thirty-two cases and the first
I I

2 ANALYSIS OF CASES OF PARONYCHIA

finger in twenty-seven. The second finger was next in
order, being affected in ten cases. There were but two
cases affecting the third finger; one affecting the fourth
finger; two affecting the first, second and third; and one
affecting the second and third. The last three cases were
of the first variety, onychia cutanea. One of them was
caused by pricking the finger in sewing. This was very
trivial and got well spontaneously. The other two were
caused by suppressed menses and were soon cured by
nitrate of silver and poultices. Thus, not only the hand,
but the fingers which are most used are most liable to
paronychia.

In sixty-three cases the ages of the patients were
noted.

I found but three cases under fifteen years of age. One
of these patients was two years of age, another three years
and another eleven years. There were thirty-eight cas.es
from fifteen years to thirty; nineteen from thirty to forty-
five; two from forty-five to sixty, (one aged forty-eight and
the other fifty) ; and one from sixty to seventy-five, (aged
sixty-one).

According to these facts, paronychia is rarely met with
in patients under fifteen years of age or over forty-five;
although it may occur at the age of two or three years or
as late as sixty-one. The favorite age appears to be from
fifteen to thirty, at which period nearly two-thirds of the
cases, where the age was recorded, were observed. It is by
no means infrequent, however, from thirty to forty-five, at
which period nearly one-third of the cases have occurred.

In sixty-three cases the occupation of the patient was
recorded.

In all but seven of these cases, the patients were en-
gaged in occupations requiring considerable manual labor.
These seven exceptions were a clerk, a clergyman, a doctor,.
a student of medicine, a female teacher and two children
at school. The remaining fifty-seven were mechanics,
laborers or housemaids. Of these there were twenty-
three housemaids, five housewives, five seamstresses and
two laundresses. Of the males there were five shoemakers,
four laborers, two sailors and two blacksmiths.

By far the largest number of cases of any one occupa-
tion was the number of housemaids, twenty-three out of

ANALYSIS OF CASES OF PARONYCHIA 3

sixty-three, more than one-third of the entire number, and
nearly five times the number of cases of any other occupa-
tion, five being the next highest number.

In fifty-one cases the probable cause of the affection
was recorded.

Under this head I find the occupation recorded as the
cause in twenty-three cases. Of these, nine were accus-
tomed to housework, scrubbing, etc. One of the patients,
a shoemaker, says that shoemakers are pecuHarly hable to
paronychia from turning boots inside out. A similar state-
ment was made by another patient, who said that lathers
and plasterers were liable to it, from driving small nails and
frequently bruising their fingers.

Five cases were caused by bad health; two cases were
the result of slight wounds; two cases were caused by sup-
pressed menses. These were of the first variety, par-
onychia cutanea, and were treated with nitrate of silver and
poultices. One case, a boy three years old, was caused by
his being deprived of meat under the impression that he
would thus avoid the cholera. He had been accustomed
to meat diet and ordinarily was healthy; but now he has a
paronychia and cankers in his mouth and nose. A clergy-
man brought on a felon by rowing a boat; a school girl, by
practicing on the piano; and a housemaid, by washing
dishes. One case occurred after an attack of ship fever.
Another case, a seamstress, occurred in a patient of a
scrofulous diathesis who had an anal fistula.

From the foregoing facts it is seen that the causes of
paronychia are various. The most frequent causes, how-
ever, are exposure of the hands to hot water, as in washing
dishes, or a slight hurt or bruise. In forty-one cases the
causes were of this description. More rarely the cause is
general or constitutional. In ten cases the causes were re-
corded as bad health, ship fever, suppressed menses, etc.

Of the entire number of cases one was not properly a
paronychia but was a fungus at the root of the nail; eight
were of the first variety, paronychia cutanea; five were of
the first and second variety, cutanea and cellulosa; and the
remaining sixty-seven were of. the second, third and fourth
varieties, cellulosa, tendinosa and osteosa. In the case of
the fundus at the root of the nail nothing is recorded but

4 ANALYSIS OF CASES OF PARONYCHIA

that on the twenty-first day the fungus was the size of
a pea.

The cause was recorded as constitutional in three of the
five cases, which were of the first and second varieties com-
bined. There was no record, under this head, in the re-
maining two cases. In three of these cases the treatment
was merely the application of nitrate of silver; one case dis-
charged spontaneously on the eighth day, but the inflam-
mation extended to the areolar tissue, pus was formed and
it was opened on the fourteenth day; in the remaining case
there was no record under the head of treatment. All these
cases resulted in perfect cures.

Of the eight cases of the first variety, paronychia cuta-
nea, six were caused by slight injuries and two were de-
pendent upon constitutional causes. Six were treated with
nitrate of silver and poultices; one, with poultices only;
and one got w-ell spontaneously. One, however, was
opened before the nitrate of silver was applied. Four of
these cases resulted in perfect cures, one of them, in the
loss of the nail, and the remaining three appear to have been
lost sight of.

In the sixty-seven cases which were of the second, third
and fourth varieties, I shall consider only one feature in the
treatment; namely, w^hether it w^as opened or not and
how long after the onset of the disease before it was
opened. The other measures of treatment were so imper-
fectly recorded that their consideration would be of little
value.

In fifty-five cases the results w'ere recorded. Thirty-
six resulted in perfect cures; and nineteen, either in loss of
part of the finger or in anchylosis.

Of the thirty-six cases twenty-nine were opened; in the
remaining seven cases there was no record under this head.
In twenty-seven cases pus had been formed. The remain-
ing nine did not suppurate.

Of the twenty-nine cases where the finger was laid open,
ten were opened on the seventh day. Eight of these had
suppurated and tw-o had not. Seven were opened on the
tenth day; three on the fourteenth day; two on the thir-
teenth day; one on the eighth day; one on the eleventh day;
and one on the fifth day. All of these had suppurated.
Two were opened on the fourth day, one having suppurated

ANALYSIS OF CASES OF PARONYCHIA 5

and one not. One was opened on the third day and one on
the second day, neither of them having suppurated.

In the nineteen cases where the cure was imperfect,
twelve were opened and in seven there was no record
under this head. One was opened on the twenty-eighth
day; one on the twentieth day; one on the fifteenth day;
one on the fourteenth day; two on the seventh day; and one
on the fourth day. In the last case no pus was found. One
case discharged spontaneously. This case was treated by
an empiric, who was prosecuted and mulcted in damages
for not opening the finger. The case resulted in a loss of
the entire finger.

From the results of these fifty-five cases it is seen that
a perfect cure may be expected in the majority of cases.
In the cases which resulted in perfect cures only six out
of twenty-nine were opened after the tenth day; seven were
opened on the tenth day; ten on the seventh day; and one
was opened as early as the second day, before pus had been
formed. None were opened later than the fourteenth day.
But in the cases where the cure was imperfect, one was not
opened at all; seven were opened from the fourteenth to
the twenty-eighth day; two only were opened as early as
the seventh day, and one on the fourth day.

These facts show the importance of opening the finger
at least as early as the tenth day; and it seems, indeed, to be
proper to do so as soon as the disease becomes established,
even before pus has been formed.

INFLAMMATION OF THE FINGER OF THE SAME CHARACTER
AS PARONYCHIA, BUT NOT IN THE LAST PHALANX

Dr. Hamilton recorded eighteen cases which came
under this head. In nearly every particular they are the
same as paronychia proper; but as the number of these
cases is large, it may be as well to consider them by them-
selves.

As in paronychia, female patients predominate, ten
being females and eight males. The age at which they
seem to be most liable to the affection is also the same. No
case occurred under fifteen years ; twelve cases from fifteen
to thirty; three from thirty to forty-five; two at thirty-two
years; and one at thirty-seven. No cases occurred after
the age of thirty-seven.

6 ANALYSIS OF CASES OF PARONYCHIA

The right hand was affected in eight out of ten cases,
where the hand was noted. Out of thirteen cases the
thumb was atTected in one case; the first finger in one case;
the second finger in six cases; the third finger in five cases;
but in no case was the fourth finger afifected. Here is a
diliference from paronychia, w'here the thumb and first fin-
ger were aft"ected in a great majority of cases. I can see no
cause for this difierence, except, perhaps, that the causes
which produce this affection appear to be more purely acci-
dental than in paronychia and not so much due to the oc-
cupation of the patient; and that the last phalanges of the
thumb and forefinger are most used, not the entire finger
and thumb, while the other phalanges of the second and
third fingers are, perhaps, more liable to accidental injuries
than the first phalanx of the thumb or the first or second
phalanges of the forefinger.

Of sixteen cases the first phalanx was affected in four
cases; the first and second in one case; the second in five
cases; the second and third in one case; and the meta-
carpo-phalangeal articulation in five cases. This shows
that the first and second phalanges are about equally
liable to it; and also the metacarpo-phalangeal articula-
tion.

As regards the occupation of the patients, it is seen
that the same classes of society are affected with this dis-
ease as those affected with paronychia. Here, also, house-
maids and housewives predominate. Of seventeen cases
there were six housemaids, three housewives, two sailors,
tW'O stone cutters, one cabinet maker, one male cook, one
cooper and one clergyman. The clergyman is the one
referred to in the cases of paronychia. This affection oc-
curred wath the paronychia and was due to the same
cause; namely, rowing a boat.

As regards the causes which operated to produce the
disease, of ten cases where the causes were noted, in five
the occupation was recorded as the cause. These five
cases embraced four housemaids and one cabinet maker.
In one case the cause was a slight cut; in another a
slight burn; in another a slight bruise; and another was
caused by rowing a boat.

Fourteen cases w^re recorded as having been opened:
two, eight days after the beginning of the disease; five.

ANALYSIS OF CASES OF PARONYCHIA 7

seven clays after; six, five days after; and one, three days
after.

All had suppurated, where this point was noted, except
one case.

Ten cases were recorded as resulting in perfect cures;
and one, as resulting in a permanent contraction of the fin-
ger. This last case was opened on the seventh day; but
afterward the finger became very much inflamed and suppu-
rated profusely.

This afifection differs from paronychia only in the situ-
ation of the inflammation. It is of precisely the same char-
acter and demands the same treatment; namely, when the
inflammation is not superficial, an early and free opening.
It appears, however, to be rather less formidable than par-
onychia, and the results usually are much more favorable.
In only one of eleven cases of inflammation of the first or
•second phalanges was the cure imperfect; and in this case
the inflammation ran very high after the finger was opened,
and resulted in permanent contraction of the flexors; while
in nineteen out of fifty-five cases of paronychia proper, the
cure was imperfect, and in some of these cases the last pha-
lanx, or even more of the finger, was lost. Dr. Hamilton
informs me, however, that in two or three cases, not record-
ed, he has seen an entire phalanx destroyed by necrosis.

PARONYCHIA MALIGNA

I have records of seven cases of paronychia maligna.
Six of these cases were recorded by Dr. Hamilton, and one
case I recorded at the clinical lectures by Prof. Gross, of
the University of Louisville.

Case I. — Joseph Carnin, aged nine years ; admitted to the Buf-
falo Hospital of the Sisters of Charity, Oct. 19, 1848. Habit scrofu-
lous; the extremity of the great toe of the left foot was swollen,
red and sHghtly tender ; the nail was black, rotten as pasteboard,
and stood directly up from the matrix. This has been his condi-
tion for about a year.

A bread and water poultice was applied for the first twenty-
four hours, and from this time ung. hyd. rub. or the ung. hyd. nit.
was applied daily to the foot. The diet was generous and he was
allowed occasional exercise. Under this treatment the malady
gradually disappeared, the cure being accomplished in about three
months.

Case II. — Geo. Vangu, aged seven years. He had scarlatina
six months ago and was very ill but now looks healthy. The par-

8 ANALYSIS OF CASES OF PARONYCHIA

onychia began soon after his recovery from scarlatina. The nail is.
black and rotten ; the affection is seated on the second finger of the
right hand. Cause, constitutional and local. Treatment has been
poultices, unguents, caustics, etc., etc. Corrosive sublimate wash
increased the irritation; poultices gave most relief. Result is un-
known.

Case III. — Thomas O'Connor, aged six years. Five weeks ago.
he split the nail of his third finger ; one week since, he bruised it.
It has been treated with poultices. The nail became black and fell
off but was reproduced, and of the same character as before, black
and rotten. In this condition the finger remained many months,
under different plans of treatment. Soothing poultices gave most
relief, especially when combined with tonics and outdoor exercise.
He was eventually cured.

Case IV. — Henry W. Putnam, aged nine years. Disease af-
fects the thumb. Cause, constitutional and local. As regards treat-
ment, almost everything which has been recommended was tried.
Six nails have fallen off successively since the disease began. The
end of thumb is flat and the sides are puffed out and of a purplish
red color ; the lower half of nail is black and rotten ; there is ulcera-
tion under the nail; the parts in the vicinity are red and puffy.
The result in this case was a cure.

Case V. — Williams, male, aged five years. Cause, probably con-
stitutional. He was apparently in good health but had slight erup-
tions on various parts of his body. It has been treated with caustics,
arsenic, corrosive sublimate, poultices, tonics, hyd. chlor. mite, etc.,.
etc. The ulceration did not cease when the matrix of the nail was
gone. Arg. nit. in substance, was first applied ; but this only in-
creased the irritation ; hyd. chlo. corros. was then applied, with the
same result. The end of the thumb was then shaved off but the
ulceration attacked the stump, and it was finally necessary to ampu-
tate the last phalanx, when the wound slowly healed.

Case VI. — Wm. Fitzgerald, aged eight years. He has parony-
chia maligna affecting the second finger of the right hand. Cause,
constitutional and local. He ran a sliver of wood under the nail
four months ago. It has been poulticed occasionally. The finger
presents the usual appearance except that the nail is not blackened.
He has a scrofulous ulceration and his mother is scrofulous. The
poultices, with good diet and cleanliness, had the best effect. This-
case was cured after several months.

Case VII. — Catharine Hynes, aged nine years, has paronychia
maligna affecting the great toe of the left foot. Cause, constitu-
tional and local. She has a scrofulous appearance and received a
severe contusion upon the toe. The nail was removed by Prof.
Gross, and the toe has the characteristic shovel shaped appearance.
Treatment was the local application of blue wash, and slight mer-
curialization.

I saw the case some days after and it was progressing favor-
ably.

This case I saw at the Louisville Marine Hospital, in 1854. It
was treated by Prof. Gross.

ANALYSIS OF CASES OF PARONYCHIA 9

Paronychia maligna, according to these observations, is
a disease pecuHar to children. Of the foregoing cases none
were more than nine years of age. Three cases were nine
years of age, and in one case the age was eight years.
There was one case of seven years; one case of six years;
and one case of five years of age. There were no cases of
less than five years of age.

All the cases recorded by Dr. Hamilton were males;
and the single case which was seen by myself was a female.
This shows a very great predominance of males.

The affected hand or foot was not noted in a suf^cient
number of cases to make its consideration of value.

The great toe was affected in two cases; the thumb in
two cases; the second finger in two cases; and the third fin-
ger in one case. Thus the hand was affected in five cases,
and the foot in only two; showing that the disease was
much more frequently seated in the finger or thumb than
in the great toe, which I believe is contrary to the general
opinion. When the foot was affected it was always in the
great toe; but in the cases where the hand was affected it
attacked the thumb or second and third finger. No cases
were recorded of the disease seated in the first or fourth
finger.

In all these cases but one the cause appeared to be
either purely constitutional or at least partially so. In one
case, however, the cause was apparently local (Case IV,
H. W. Putnam), though the progress of the disease shows
that the system was somewhat at fault. In three cases the
cause was pvtrely constitutional; and in three cases it was
constitutional and local.

Such a variety of treatment has been practiced in these
cases that its consideration, with reference to results, is of
little value. Tonics, cleanliness and soothing applications
appear to have had the best effect; and mild mercurial ap-
plications were used with advantage in two cases in connec-
tion with outdoor exercise, tonics and poultices. Caustics,
where they have been used, have not been productive of
any good effects but appear rather to have aggravated the
disease.

Four cases (I. III. IV. and VI.) are known to have re-
sulted in perfect cures. In three cases tonic measures and
poultices were employed. In addition to these measures,

lo ANALYSIS OF CASES OF PARONYCHIA

in one case, ung, hyd. rub. dilutiim was used. In one case
(V.) it was necessary to amputate the last phalanx of the
thumb. In one case (II.) the result was unknown. I saw
Case VII. several times at the Louisville Marine Hospital.
It was progressing favorably and probably resulted in a
perfect cure.

From these facts it may be inferred, that although the
disease is likely to be protracted and tedious, yet with
proper care a perfect cure is to be expected. Amputation
of the affected part will rarely be necessary.

II

PHENOMENA OF THE CAPILLARY CIRCU-
LATION—AN INAUGURAL DISSERTATION
LAID BEFORE THE FACULTY OF THE
JEFFERSON MEDICAL COLLEGE IN FEB-
RUARY, 1857

Published in the " American Journal of the Medical Sciences" for July, 1857.

The Statements which I shall make from my own ob-
servation concerning the capillary circulation are based
upon examinations made from time to time during the past
summer, eight of which have been carefully recorded. The
recorded observations were made on the web of the frog,
although I made examinations of the various other parts
where the circulation can be conveniently exhibited, to
which I shall refer.

The microscope used was the large instrument of
Nachet; and unless otherwise stated, with a magnifying
power of 165 diameters.

I shall first point out what I have found to be the
most convenient methods of conducting examinations of
the circulation in the frog, then proceed to describe the
various phenomena of the circulation as viewed by means
of the microscope, and then draw my deductions from these
observations.

The parts of the frog which I have subjected to exami-
nation are the web of the foot, the tongue, the peritoneum
and the lungs. All parts except the peritoneum should be
examined by transmitted light; but in examining the cir-
culation in the latter situation it is necessary to.use reflected
hght.

It is exceedingly inconvenient to miake observations
while the frog has the power of motion, and in securing it
to the frog-plate in a proper position, we are likely to inter-
rupt or modify the circulation by constricting the vessels

12 THE CAPILLARY CIRCULATION

with the Ijands which we must use. Under these circum-
stances medicated solutions can not conveniently be ap-
plied to the entire surface, and mechanical or chemical
irritation of any part occasions struggles which greatly
increase the difficulty of the experiment. By breaking up
the medulla oblongata, or even the posterior part of the
brain (for it is not easy to invariably reach the medulla
without some practice), one is enabled to observe all the
phenomena of the circulation with great facility, avoiding
the necessity of forcibly retaining the frog in the desired
position, with the consequent liability to constriction of the
vessels and shifting of the field of observation. I shall here-
after refer to the experiments of E. Brown-Sequard, of
Paris, and two of my recorded examinations, which show
that observations of the circulation may be made with as
much accuracy on a frog after the medulla has been de-
stroyed as though it had not been subjected to the opera-
tion. The operation may be performed by introducing a
dissecting needle into the cranium, a line or two behind the
eyes, passing it backward and a little downward to the
articulation of the spine with the skull, and then thoroughly
breaking up the medulla. The web of the foot may be
examined in the following manner: First break up the me-
dulla oblongata in the manner just described; the frog will
then remain perfectly motionless in any position. The w^eb
may be stretched over the opening in the frog-plate and
secured in position by means of pins, care being taken not
to extend the web too forcibly, and to put no pins above
the foot, but nearly at the extremities of the toes, as in
either case the circulation may be disturbed. The part
should then be moistened, and the lenses of the microscope
protected from the evaporation by a glass cover, broken to
fit between the toes.

The entire surface of the frog should be moistened from
time to time with cool water.

The magnifying power best adapted to such observa-
tions, is one of 150 to 200 diameters.

In examining the tongue, draw it out of the mouth and
stretch it so as to form a thin transparent film by means
of the forceps and pins. The circulation may be exhibited
in the peritoneum by merely exposing that membrane and
examining it wath a power of 60 or 70 diameters by reflect-

THE CAPILLARY CIRCULATION 13

ed light. The method of exhibiting the circulation in the
lungs of the frog is much more complicated and difficult
than either of the preceding experiments, but when suc-
cessfully performed, it is one of the most beautiful and curi-
ous demonstrations in the whole range of microscopic
work.

Dr. Robert Willis, in his edition of " Wagner's Physiol-
ogy," refers to the appearances of the pulmonary circula-
tion in the water newt. He directs that the newt be stran-
gled after an inspiration. " The abdomen is then to be laid
open, and the entire animal, being held in the hands, is
placed upon a glass plate as a ' porte-objet,' and one of the
lungs brought into the field of view." He observes, how-
ever, that the circulation lasts but a short time. The frog
appears to me to be a much better subject for this experi-
ment ; and as I have never seen the process of showing the
pulmonary circulation in this animal detailed in the books,
I shall describe it with some minuteness as practised by
Prof. John C. Dalton, of Xew York, and as repeated fre-
quently by myself.

In undertaking it, a large sized frog should be selected.
After having broken up the medulla oblongata, a ligature
is to be placed around the larynx in the following manner:
The mouth being widely opened, the larynx is seen just in
front of the oesophagus. A ligature is now carried just
under the mucous membrane by means of a small curved
needle. This is effected by making four or five stitches,
the needle being introduced at the point where it came out
at each preceding stitch, so that the ligature shall smoothly
encircle the larynx and its extremities emerge at the same
point. This being done, a small blowpipe is introduced
into the windpipe and the ligature is held in readiness to be
drawn tight by an assistant when required. The lungs
must now be moderately distended and the ligature tight-
ened, at the same time removing the blowpipe. If the side
is now carefully opened the lung will protrude and may
be examined by transmitted light.

It is very much more difficult to exhibit the circulation
in the lungs than in any other part. The chief difficulties
to be encountered are the following: First, it is no easy
matter to fix the ligature properly around the larynx; but
when this has been done, if the lungs are distended too

14 THE CAPILLARY CIRCULATION

forciljly. they will either burst or the circulation will be
greatly impeded; and if not distended sufficiently, they will
not protrude when the side is opened. There is, also, always
some difficulty in introducing the blowpipe, and its delicate
orifice is often occluded by the secretion of the part. When
successful, however, in exhibiting the circulation in the
lungs, the capillaries are seen encircling the air-cells, which
are quite large in the frog. This is an extremely beautiful
and interesting sight — but more as a scientific curiosity
than as a field for useful investigation. It was observed by
Dr. Willis, and confirmed by Wagner and Gluge, that the
transparent plasma which is found occupying the space next
to the walls of the capillaries in most situations, while the
blood-disks occupy the centre, constituting the still layer
of Kirkes, is not observed in the capillaries of the lungs;
in other words, the vessels are crowded to their very walls
with corpuscles.

For this remarkable deviation from a general law they
ofifer no explanation.

I have never observed this peculiarity, as my attention
was not directed to it when examining the pulmonary cir-
culation. Those who believe that the heart is solely in-
strumental in propelling blood through the capillaries
would not be able to account for this phenomenon; but
it seems to me it can be explained in the following manner:
The blood circulating in the systemic capillaries nourishes
the tissues by the liquor sanguinis, and thus the attract-
ive vital force operates on this constituent. The plasma
then is nearest the tissues and next the walls of the vessels;
but the pulmonary capillaries are for the aeration of the
blood, a process which is effected by the globules and not
by the plasma, since the great mass of blood is not sent to
the lungs for purposes of nutrition, but for aeration; hence,
the globules, which here feel the force of attraction for oxy-
gen, occupy the space next the walls of the vessels.

Taking the view which I do of the causes of the capil-
lary circulation, this explanation is satisfactory.

Before proceeding to describe minutely the phenomena
of the capillary circulation, I shall briefly consider the ana-
tomical structure of the capillaries and of the blood.

Ch. Robin recognizes three varieties of capillaries. The
first variety is -j-sVo to -g-j-Q of an inch in diameter, and

THE CAPILLARY CIRCULATION 15

is composed of a transparent homogeneous membrane,
Tswo of ai'' iiich in thickness, with nuclei, and sometimes
nucleoli, projecting into the calibre of the vessel. The nu-
clei are oval, with their long diameter in the direction
of the vessel. These are embraced under the head of the
" true capillaries " of Prof. Kolliker.

The second variety, M. Robin describes as having two
coats: the membrane with the longitudinal nuclei of the
first variety, and investing it, a second membrane with
transverse nuclei. The diameter of the second variety
varies between -^^ and ^^ of an inch. This variety also
probably comes under the head of the " true capillaries "
as described by Kolliker, though he does not mention the
second investing membrane.

The third variety, M. Robin calls venules and arteri-
oles; Kolliker, venous and arterial transitionary vessels.
Their diameter is -gV to iV of an inch, and they have
added to the two coats of the second variety a third coat of
areolar tissue. It seems to me most convenient and proper
to consider the first tw-o varieties of M. Robin, or the " true
capillaries " of Prof. Kolliker, simply as capillaries (their
tunic being a prolongation of the inner coat of the arteries),
and the third variety of M. Robin as venules and arterioles.
One may easily distinguish the arterioles from the venules,
by noticing that the arterioles give off branches, while the
venules receive them; that the arterioles diminish in size
in the direction of the current of blood, while the venules
increase in size.

The blood consists of a transparent plasma holding two
kinds of corpuscles in suspension, called the red and white,
or colorless. In the human subject the red corpuscles are
disks like pieces of coin, but thinner in the centre than at
the edges. They have no nuclei, though the difference in
thickness causes the centre to appear dark when the edges
are in focus. They are j-gig-g- of an inch in diameter. The
white corpuscles are larger than the red, being j-^\-^ of an
inch in diameter; they are globular, white and granular.
If water is applied to them they are rendered transparent,
and we can distinguish a nucleus. They are much less
abundant than the red corpuscles. In the frog, the red
corpuscles are oval and large, with a central rounded nu-
cleus. They are y^Vo- o^ ^'"i ^"^^'^ i" their long diameter.

i6 THE CAPILLARY CIRCULATION

The white globules are smaller and proportionally more
abundant than in man. The blood-disks in nearly all ani-
ma are red by reflected light, but of a pale amber color by
transmitted light.

In a paper communicated to the '' Medical Examiner,"
August, 1852, by E. Brovvn-Sequard, M. D., of Paris, en-
titled " Experimental Researches applied to Physiology
and Pathology," I find some very interesting observations
on the effect, or more properly the absence of effect on the
capillary circulation, of the section of various nerves. This
observer, with the assistance of Dr. Siebert, found, " after
the section of all the nerves (the sympathetic and cerebro-
spinal) in the legs of a number of frogs, that there was no
appearance of trouble in the capillary circulation, either in
one hour or three or four days after the division of the
nerves." He concludes from another experiment that the
nervous action (that of the sympathetic as well as the cere-
bro-spinal nerves) is not necessary for the change of col-
or of the blood in the capillaries. It is proved by this ex-
periment that the capillary circulation is not immediately
dependent in any measure on nervous influence.

A curious fact has been observed by Bernard; viz., that
after a section of the sympathetic in the neck, the corre-
sponding side of the face, and more particularly the ear, be-
comes warmer and more sensiti\-e than the other side. The
bloodvessels appear more abundant than before and are
enlarged. Brown-Sequard has repeated this experiment
and concludes that the increase in temperature and sensi-
bility is due merely to passive dilatation of the vessels from
paralysis of their coats and consequent congestion. I have
myself seen the experiment performed by Prof. Dalton, of
New York, and concur with him in the opinion that the
increase in temperature and sensibility is due rather to an
exaggeration of the nutrition of the parts; for specimens
of blood drawn from the two ears have been compared,
and there has been found a marked difference in their actual
chemical composition.

These considerations are interesting in connection with
animal heat as produced by the molecular changes in the
various tissues, and appear, also, to bear in some measure
on the subject of the capillary circulation.

I shall hereafter take the ground that the capillary cir-

THE CAPILLARY CIRCULATION 17

dilation is in a great measure dependent upon an attrac-
tion of a chemico-vital character between the tissues and
the nutrient fluid.

Now, if the nutrition of the part is augmented, the con-
gestion is due to the greater attraction of the tissues for the
blood, the capillaries being first affected by its influence.
The nutrition is affected, because the blood actually under-
goes greater changes than on the other side. The capil-
lary circulation, then, in this case seems clearly to be in a
measure dependent on the process of molecular regenera-
tion and disintegration. There is no new action induced
in the part, but simply an augmentation of the usual pro-
cesses; and if this is so, a cause of the capillary circulation
is a chemico-vital attraction of the tissues for the blood.
The fact that there can be a greater supply of blood, cir-
culating with greater force, on one side of the body than
in the corresponding part on the other side, seems to me
an insuperable objection to the idea that the heart alone
circulates the blood in the capillaries; but I have antici-
pated, in some degree, the points which I shall hereafter
consider more fully.

When I began to describe the manner of making ob-
servations on the capillary circulation in various parts, I
assumed that destruction of the medulla oblongata had no
appreciable effect on the capillaries. Brown-Sequard has
demonstrated by experiment, that frogs are able to live
perfectly well for three or four months after extirpation of
the medulla, and that all the functions, except pulmonary
respiration, go on apparently as usual.

Before I met with these observations, I made two ex-
periments with reference to the reliability of observations
made on a frog after breaking up the medulla or the pos-
terior part of the brain.

In my first experiment the posterior part of the brain
was broken up in an unsuccessful attempt to reach the
medulla.

Observation I. — The circulation was observed for seven hours
and was but slightly retarded when the experiment was concluded.
For the first two hours the circulation appeared as usual. I have
made many unrecorded observations on this point and have always
arrived at the same result : I have introduced a dissecting needle
at the back of the head, sometimes reaching the medulla and some-
2

i8 THE CAPILLARY CIRCULATION

times not, but always rendering the frog perfectly quiet and man-
ageable; and I have been unable to discover any effects upon the
circulation or the phenomena produced by irritants.

After making this experiment I made several dissec-
tions so as to be able to reach the medulla oblongata with
certainty, and succeeded in destroying the medulla in the
following observations:

Observation II. — I examined the circulation for five hours
M^ith the same results as in the preceding experiment. There was
no alteration from the appearances of the circulation in the unin-
jured frog, at least for the first two or three hours.

From these observations added to my unrecorded ex-
periments I have no hesitation in saying that observations-
on frogs after breaking up the medulla oblongata or the
posterior part of the brain are quite as valuable as those
made on uninjured frogs; therefore all the subsequent ob-
servations were made after breaking up the medulla, un-
less otherwise stated.

Dr. Wilson Philip made an experiment which is inter-
esting, though not throwing any light upon the causes of
the capillary circulation. " While Dr. Hastings was observ-
ing the circulation, he crushed the brain by the blow of a
hammer. The vessels of the web instantly lost their power,
the circulation ceasing; an effect which we have seen can-
not arise from the ceasing of the action of the heart. (Dr.
Philip here refers to experiments by which it is ascer-
tained that the blood will circulate for several minutes
after the interruption of the heart-action.) In a short time
the blood began to move, but with less force." I may
here add the notes of a similar experiment performed by
myself:

Observation III. — The brain of the frog was crushed while
Prof. Flint was examining the circulation, which was brisk and
regular ; the motion instantly ceased, but began again in a few sec-
onds, though it proceeded more slowly. This observation in every
respect confirms that of Dr. Philip.

This, as I have before remarked, cannot be thought to
show that the capillary circulation is dependent upon nerv-
ous influence, but merely that a violent shock is able to
arrest momentarily all the vital functions. In several of my
observations, I have minutely recorded the appearances of

THE CAPILLARY CIRCULATION 19

the capillary circulation and have noticed the following
phenomena :

Observation IV. — I examined the web of a young frog.

From a careful and prolonged examination, it is evident that
there is a difference between the modes of circulation in the arteri-
oles and the venules. The blood moves more freely in the former
and the motion appears to be dependent on an attractive force.
This is not so evident, however, here as in the capillaries; there
the blood shoots off to different parts of the tissues in a manner
which cannot be dependent upon a " vis a tergo." It also moves
much more rapidly in some of the capillaries than in others, the
velocity varying in the same vessel at different times. In the
venules, the movement is more sluggish, the globules apparently
crowding each other along, and on careful examination making a
decided contrast to the movement in the arterioles. The number
of colorless globules is greater in the venules ; they adhere to the
walls of the vessels and appear to be pushed along by the central
mass, moving very much more slowly and occasionally remaining
stationary for a time.

Observation V. — In this observation, the same points attracted
attention as in the preceding one, and in addition, the following
phenomena were noted :

A small transverse capillary, admitting but a single globule at
a time, was abruptly bent at a certain point. The globules passed
along in single file, irregularly isolated from each other, and were
bent nearly double in passing the sudden turn in the vessel. This
caused the globules to present a singular appearance at this point ;
they seemed to move by volition, like animate beings. The motion
of the globules under the above circumstances seemed to indicate
an attractive force.

In several instances the walls of the vessels were distinctly
seen ; they were perfectly motionless, evidently taking no active
part in the circulation. The darting of single globules through
small vessels, at a velocity greater than the velocity of the circu-
lation in the vessel from which they branched, was repeatedly noted.

Observation VI. — The points noticed in Observation IV were
here confirmed. I was forcibly struck with the great difference
in the velocity of the circulation in different parts of the field, both
in vessels of the same size and of unequal sizes. I also remarked
a difference of velocity in the same vessels, especially capillaries,
at different times.

An attractive force is evident; and a certain condition
of the disks is necessary in order that the force should
operate. This condition, it may be presumed, is brought
about by respiration.

The appearances of the capillary circulation in the web
of the foot may be described as follows:

When the web is subjected to examination in the man-

20 THE CAPILLARY CIRCULATION

ner already described, there are vessels of various sizes in the
field, consisting of arterioles and venules, wdiich vary most
in their diameters, and the true capillaries which are all
of nearly equal diameters. The blood is seen coursing
along these vessels with great rapidity, especially in the
arterioles, where we may observe a slight pulsatory move-
ment.

In the arterioles, blood moves with unvarying rapidity
as a general rule; and here especially we notice a space next
the walls of the vessels, which is not occupied by the red
globules, but along which the colorless globules move at
a diminished rate, appearing to have a tendency to adhere
to the walls of the vessels, and sometimes even remaining
entirely stationary for a time, to be pushed along again by
the central mass. This constitutes the " still layer " of
Kirkes.

The white or colorless corpuscles are much fewer than
the red and they move at least ten or twelve times more
slowly than the central mass. On careful examination I
have been able to note a decided difference between the
circulation in the arterioles and the venules. In the latter
the movement is not so rapid, the globules appearing to
be impelled more by a " vis a tergo " and to feel less the
" vis a fronte," wdiich seems to operate in the arterioles.
The comparative number of the white corpuscles is greater,
but the " still layer " appears to occupy a smaller propor-
tion of the calibre of the vessel.

In the true capillaries the movements are less regular
and apparently are dependent in a great measure on a force
which acts directly upon them; the "capillary power," as
it is designated by Dr. Carpenter. This will be more fully
touched upon presently in considering the causes of the
capillary circulation.

In the true capillaries the blood moves in every possi-
ble direction, at different rates of speed in different vessels
and at different times in the same vessel. In one instance
I remarked a capillary branching from a vessel at an obtuse
angle (that is, turning almost directly opposite to the cur-
rent in the main vessel), and individual globules shooting
through it with great rapidity. In many instances, I ob-
served a complete stasis in one or two of the capillary ves-
sels, but it existed only for a moment and the current began

THE CAPILLARY CIRCULATION 21

again with its original vigor. Dr. Carpenter has remarked
a stasis followed by a current in an opposite direction.

It frequently happens that a globule is caught at the
point of junction of two vessels and remains stationary until
it is carried along by the current of blood. Globules are
frequently bent upon themselves as they pass from one ves-
sel to another, but so soon as the cause is removed they
regain their original conformation.

The walls of the vessel are motionless, and they do not
take an active part in the normal circulation as was sup-
posed by some of the older writers.

Pigment-cells are observed scattered over the field,
when they, are very abundant obscuring the view of the
circulation; therefore it is best to select a light colored
frog for demonstrations.

The pavement variety of epithelium may also be seen.

This is a description of the capillary circulation as it ap-
peared to me under the most favorable circumstances:
more minute, but not otherwise differing from the ordinary
description in works on physiology.

I now come naturally to a consideration of the causes
of the capillary circulation. I say causes, because I shall
take the ground that it is not produced by a single cause;
namely, the heart's contraction, as was supposed by the
great discoverer of the circulation. While it may be that
the action of the heart is sufficient to propel the blood
through the whole round of the circulation, as is contended
by Magendie, by Dr. Allen Thompson, in the " Cyclopedia
of Anatomy and Physiology," Dr. Kirkes and others, I
believe that there are other causes which operate and are
able to carry on the circulation unassisted, as was the case
in the acardiac foetus of Dr. Houston, reported in the
" Dublin Medical Journal," 1837, where, of course, the cir-
culation was stopped at the birth of the child by the want
of due aeration of the blood.

Harvey, followed by Magendie, Kirkes and other emi-
nent physiologists, supposed that the heart was alone con-
cerned in the production of the circulation, and some very
striking arguments were made use of to prove it. It is
found that under the most favorable circumstances a very
inconsiderable force is required to propel a bland fluid from
the arteries through the capillaries and out again by the

22 THE CAPILLARY CIRCULATION

veins. The pulsative movements, which are observed un-
der some circumstances in the capillaries, is also brought
forward as an argument. Dr. Kirkes dismisses the subject
with the remark that " there is no need of an hypothesis of
any action of the capillaries for regular propulsion of the
blood through them, nor is it probable they have such an
office." This appears to me a most unphiloso])hical mode
of treating a very important subject. The circulation of
the blood is a process immediately necessary to existence;
and even admitting that the action of the heart is quite
capable of carrying on the circulation, it would not be out
of place to inquire if there be not some other force which
also operates to this end, and can take on, in some degree,
the function of circulating the blood, should the heart be-
come W'Cakened from any cause. In the performance of
that essentially vital function, respiration, we commonly
use but about one-third of the entire capacity of the lungs;
and though the lungs seem to be only aerating organs,
they divide that function with the skin. One might as well
say that as the diaphragm is sufficient to carry on respira-
tion, there is no need of supposing that there are any other
respiratory muscles.

There are several phenomena which are difficult of ex-
planation on the theory of the sole action of the heart in
producing the circulation. In the first place it is difficult
to understand how the heart could impel the blood through
the second set of the capillaries in the portal system. Then
the experiments of Dr. Dowler show that the blood prob-
ably circulates in the capillaries in patients dead from yel-
low fever, after the heart's action has ceased.

In the frog, Dr. Carpenter asserts, and I have myself
seen that the blood will circulate in the capillaries after
complete excision of the heart. Carpenter also mentions
instances wdiere the heart has suffered such a degree of
fatty degeneration or displacement that there existed
scarcely a trace of muscular fibre, and the circulation must
have been chiefly dependent on the " capillary power."
Hassall records a most remarkable phenomenon; namely,
the continuance of circulation in a portion of the tongue
which had been entirely detached from the body. He
states that while examining the tongue of a frog, a small
portion w^as torn off, which he placed between two plates

THE CAPILLARY CIRCULATION 23

of glass and was astonished to see the circulation continu-
ing in many of the smaller vessels with unabated vigor.
This phenomenon he observed for several hours, in con-
nection with several medical gentlemen ; and on examining
it the next day, preserving it under water in the interval,
the circulation still continued to some extent. This seems
almost incredible; but coming from such authority the fact
can not be doubted. Hassall appears to have made no sub-
sequent experiments with reference to this point. After
seeing this statement, I made two or three experiments,
and once saw a slight movement in a portion of the tongue
entirely detached; these experiments were not made, how-
ever, under favorable circumstances, the weather being
cold, and the frog in a state of torpor until partially aroused
by immersion in tepid water.

A case is mentioned by Dr. Carpenter of an acardiac
foetus which was subjected to examination by Dr. Houston,
where the organs were tolerably well developed, with the
exception of the heart, and the circulation could be ef-
fected only by the " capillary power." The cases which I
have described are amply sufficient to disprove the theory
that the heart is the sole cause of the circulation. In
addition, the phenomena of inflammation as seen under
the microscope; the normal appearances of the capillary
circulation, which appear to the eye to be in some measure
dependent on an attraction of the molecules of the tissues
for the blood; the experiment of the section of the sym-
pathetic in the neck of the rabbit, which I have previously
noticed, and which produced an augmentation of this at-
tractive force in the corresponding ear and side of the face;
and comparison with the circulation in some aquatic plants,
which is not dependent upon the action of a heart ; all these
go to show that the heart alone does not carry on the cir-
culation.

Prof. Draper, of the University of New York, has pro-
posed a theory in regard to the circulation, which makes
the heart of minor importance. His is the theory of capil-
lary attraction and affinity. He starts with the proposition
that, " if two liquids communicate with each other through
a capillary tube, for the substance of which they have affini-
ties of different intensities, movement will ensue; the liquid
having the highest affinity will occupy the tube, and may

24 THE CAPILLARY CIRCULATION

even drive the other from it; the same effect will ensue in a
porous object." He believes that this is the main cause of
the circulation; namely, an affinity between the blood and
the tissues; that thus the blood is forced into the veins; and
that the action of the heart is limited to filling the arteries
and presenting a supply of blood to the capillaries. The
blood circulates in the lungs chiefly on account of its
affinity for oxygen.

This theory can not be sustained. The heart undoubted-
ly has a much more important office in the production of
circulation. When a small artery is cut the blood is seen
forcing itself in a jet to a distance of several feet; and this
happens after it had entirely lost the influence of the capil-
lary force. The illustration of Prof. Dunglison; namely,
the law that fluids confined in tubes will rise to the same
level, and that thus the blood in the veins, by a simple hy-
drostatic principle, would rise as high as the right auricle in
a line with the blood in the left ventricle, shows how slisfht a
force from the heart would be propagated through the cap-
illaries to the veins and be sufficient to return the blood.

Dr. Dowler, of New Orleans, believes in a distinct capil-
lary action. In some of the experiments which he adduces
in support of his position, and which are noticed by Prof.
Dunglison in his " Human Physiology," bodies of yellow
fever patients were carried to the dissecting room a few
moments after death. " The external veins sometimes be-
came distended, and when punctured, the blood flowed in
a good stream; the operation of bleeding at the arm was
imitated, and as the muscles were moved, the blood shot
forth for some distance." Other experiments on the veins,
of a similar character, are recorded by him.

These observations seem to show that there is some
action in the capillaries after death, and inferentially during
life, which is independent of the heart's action. The entire
emptying of the arteries after death cannot be satisfactorily
explained by mere contraction of the vessels.

What causes seem to operate to produce the capillary
circulation, judging merely from the appearances under the
microscope? In the observations which I have recorded
on this point, I noted an irregularity of the movement in
the capillaries, both in different vessels at the same time
and in the same vessel at different times; the irregularity

THE CAPILLARY CIRCULATION 25

sometimes amounting to entire cessation of the circulation
in a single vessel, and then a current in an opposite direc-
tion; a shooting off of single globules through vessels
which were before empty; the darting of¥ of globules
through capillary branches with a velocity greater than
that of the blood in the main vessel; and in short, all the
phenomena which are presented to the eye seem to indi-
cate that there is an attractive force, resident in the solid
particles, which operates on the blood in the capillaries.

I am not supposing the existence of a force with the
operation of which physiologists are unacquainted. The
present school of physiology teaches that the processes of
nutrition, of molecular disintegration and of secretion are
dependent on a vital force resident in the solid particles of
the organism which are essentially vitalized. Inflamma-
tion is now supposed to be due to a perversion of this force.

What other explanation is there of the fact that every
tissue takes from the mass of arterial blood the substances
which are required for its nutrition? The blood sent to the
systemic capillaries by the heart is the same in all parts of
the body; but when the great change which is effected in
the capillaries has taken place, the blood which has thus
been rendered venous is not the same in all the veins; for
example, the blood in the renal vein is almost as florid as
arterial blood.

The existence of a distinct capillary action is now be-
lieved by the highest authorities. Lehmann believes that
a chemico-vital attraction of the blood for the tissues, to-
gether with the physical capillary attraction, produces the
movement of the blood in the capillaries and forces it into
the veins. Dr. Carpenter believes that there exists a " cap-
illary power " which is superadded to the force of the heart.
Prof. Dunglison teaches that there is an independent power
resident in the tissues about the capillaries, and that, " by
the united action of the heart, arteries and capillaries, or
intermediate system of vessels, the blood attains the veins."
Even those who recognize the heart as the only efficient
organ of circulation admit that the capillaries possess a
"distributive force;" that is. though the circulation is
effected by the heart's unassisted action, the tissues have
an attraction or affinity for the blood, which distributes
it for their nutrition to each and every part of the body.

26 THE CAPILLARY CIRCULATION

Taking into consideration everything that I have seen
bearing on this point, it seems to me to be clearly proved
that the normal capillary circulation is dependent, in the
hrst place, on the action of the heart. It cannot be denied
that the heart has a considerable share in producing ca])-
illary circulation. Taking into account the conditions of
the blood and vessels, apparently a slight force is capable
of propelling the blood through the capillary system.
When a small artery is divided, the force with which the
blood flows out is considerable and appears sufificient to
exert a decided effect on the motion of the blood in the
capillaries. It is impossible to estimate with much accura-
cy the proportional influence which the heart has in produ-
cing the capillary circulation. The vital affinity between
the tissues and the blood, which I suppose to be the other
power concerned in this function, never ceases; still, as the
action of the heart is frequently much interfered with, as
in cases of excessive fatty degeneration, and as the heart
has been removed from the frog, the capillary circulation
nevertheless continuing, I cannot think that its power is
greater than the active force, or Carpenter's " capillary
power," which I hold to be essentially concerned in the
performance of this function. The value of the heart's ac-
tion is also variable, both in different individuals and in
the same individual at different times.

The only other force which has any share in the produc-
tion of the capillary circulation, except, perhaps, a slight
suction force from the veins, is the " capillary power." This
seems to me to play the more constant and effective part.
When this ceases to act the animal dies and the blood re-
fuses to circulate in spite of the heart. This is the great vital
force of nutrition which is constantly operating and which
is so wonderful and inexplicable. It is a fact that there is
such a force and that it continually acts; but what it con-
sists of or what is its essential character is beyond the wis-
dom of man to explain. It is life. Finally, the following
inquiry suggests itself: What conditions are necessary to
the healthy performance of the capillary circulation?

First, a healthy condition of the vital particles, which
is produced by healthy nutrition. Second, a certain con-
dition of the blood, which is produced by respiration.

No arguments appear to be necessary to prove the

THE CAPILLARY CIRCULATION 27

former statement; but I have made experiments, which I
shall proceed to describe, which conclusively establish the
second point.

The following experiment, made by Dr. J. Reid, and re-
ported in the " Edinburgh Medical and Surgical Journal,"
April, 1 84 1, is quoted by Dr. Carpenter:

Dr. Reid found that when the ingress of air through the
trachea of a dog was prevented and asphyxia was pro-
ceeding to the stage of insensil)ility, the pressure in the
femoral artery, indicated by the hemadynamometer, was
much greater than usual.

Upon applying a similar test to a vein, however, the
pressure was proportionally diminished; whence it became
apparent that there was an unusual obstruction to the pas-
sage of the venous blood (the blood being venous in the
arteries) in the systemic capillaries.

Before seeing an account of this experiment, I had made
the following observations, carefully recording them, with
reference to the same point:

Observation VII. — The medulla of a medium-sized frog was
broken up and the web submitted to microscopic examination. The
frog was bathed with sulphuric ether, care being taken not to allow
the ether to touch the web under examination, and the circulation
was watched for ten minutes. No effect could be discovered. The
object of this experiment was to determine whether the phenomena
in the succeeding experiment were in any degree dependent on the
ether which is contained in collodion.

The frog was then painted over with an impermeable coating
of collodion, care being taken as before not to touch the web. The
effect on the circulation was immediate. It instantly became less
rapid, until at the expiration of twenty minutes it had entirely
ceased.

The smaller vessels were the first to become affected, the larger
arterioles resisting it longest. One of the first effects was a pul-
satile movement in vessels where the blood had previously flowed
in a continuous stream, showing, as it seemed, that the attractive
force was lost, but that the heart's action was felt.

The fact of the first arrest of the blood in the capillaries seemed
to indicate that the blood was unfit to supply the wants of the tis-
sues, and that the attractive force had ceased to be operative. The
arrest of the circulation was steady, and at the expiration of twen-
ty minutes the motion had entirely ceased.

The entire coating of collodion was then instantly peeled off,
and the effect on the circulation was instantaneous. Quite a rapid
circulation immediately began, but it soon began to decline, and in
twenty minutes had almost ceased. The heart was now exposed

28 THE CAPILLARY CIRCULATION

and found contracting regularly. In this experiment all respiration
was abolished, the medulla being broken up and an impervious coat-
ing applied to the entire surface.

Ohservation VIII. — I painted a frog with a thick coating of
collodion without destroying the medulla. It struggled vigorously
at first, but soon became quiet and the web was put under the mi-
croscope.

The circulation was affected in the same manner as in the pre-
ceding experiment and entirely ceased in twenty-five minutes.

During the first few minutes the nostrils dilated and contracted
rapidly but soon became motionless. Care was taken not to ob-
struct the nostrils with collodion, although it was applied effectually
to all other parts except the foot under observation.

The experiment of Dr. Reid proves this fact inferen-
tially; namely, that the blood, deprived of oxygen, as in
asphyxia, is retarded in the systemic capillaries; but the
experiments just related bring the processes directly under
the eye; and one can see clearly that when the blood is not
aerated it will not circulate, although the heart contracts;
and that it is retarded in the capillaries. My second ex-
periment demonstrated the comparatively small part which
the lungs of the frog take in respiration; the blood circu-
lating in the frog, in which the pulmonary respiration was
not interfered with, only five minutes longer than in the
frog after destroying the medulla. Capillary circulation
will go on in the lungs of the frog after tying the trachea,
as I stated when describing the circulation as seen in vari-
ous parts of the animal, the blood being suf^ciently aerated
by means of the skin.

Thus it is experimentally proved that an oxygenated
state of the blood is an indispensable condition for its circu-
lation through the capillaries. When the process of respi-
ration, or aeration of the blood, is interrupted, the blood
cannot circulate. This is an acknowledged fact; but I have
shown, by the preceding experiments, that in asphyxia the
impediment to the circulation is in the capillaries; that
the condition of oxygenation is necessary to the per-
formance of the vital functions; and it may be that the en-
tire want of the " capillary power " throws all the onus on
the heart, and that the heart is insufficient for the labor.
In one of my experiments, after the capillary circulation had
entirely ceased, the chest was opened and the heart was
found beating regularly.

Ill

EXPERIMENTS ON THE RECURRENT SENSI-
BILITY OF THE ANTERIOR ROOTS OF THE
SPINAL NERVES

Published in the " New Orleans Medical Times," in 1861.

There are few facts in physiology better known and
more generally admitted than those which have refer-
ence to the properties of the two roots of the spinal
nerves. The anterior roots are motor and the posterior
roots are sensory. Like most important discoveries,
however, the credit of its authorship has been somewhat
disputed, though it is now usually conceded to Sir Charles
Bell. It is a curious fact, nevertheless, that in 1809, two
years before the appearance of Sir Charles Bell's first
essay, Mr. Alexander Walker, an English physician, ad-
vanced the idea that the two roots of origin of the spinal
nerves had dififerent properties; but he supposed that the
posterior roots were motor and the anterior roots sen-
sory. To support this view, which was a mere supposi-
tion, Walker brought neither physiological nor patho-
logical proofs; but in 181 1, Charles Bell made the great
discovery with which his name is connected; viz., that
the posterior roots conducted sensations and that their
irritation produced no movements, while the anterior
roots were motor, as proved by the occurrence of mus-
cular movements when they were stimulated. Bell, how-
ever, was not a vivisector; his experiments were chiefly
on rabbits, which he killed suddenly, opened the spinal
canal and irritated the posterior and anterior roots of
the nerves, the experiments resulting, as just stated, in
movements of muscles when the anterior roots were
stimulated, and none when the same stimulation was ap-
plied to the posterior roots. These experiments were

repeated by French and German physiologists, among

29

30 RECURRENT SENSIBILITY

whom were Miiller, Valentin, Magendie and Longet.
Longet, especially, carried Bell's experiments on the
nerve-roots to the columns of the cord and demonstrated
that the anterior columns were motor while the poste-
rior were sensory. He also made a number of confirma-
tory experiments upon the roots of the nerves in living
animals.

The experiments which are chiefly to be noticed in
the present communication were made by Magendie;
who, though many physiological facts had of course al-
ready been arrived at by experiment, may be said to be
the father of the experimental school of physiology. He
made experiments, which were published in 1822, upon
the roots of the spinal nerves, and found that while the
posterior roots were purely sensory, the anterior roots,
were not, in all of his observations, purely motor, but some-
times possessed a slight degree of sensibility. These ex-
periments he repeated in 1839 and was able to establish at
that time a certain degree of sensibility in the anterior roots.
He also showed that the facial possessed some sensibility
and that this was derived from the fifth pair. This he called
the " recurrent sensibility; " and these experiments tended
to show that the views of Sir Charles Bell and his followers
had been too exclusive; that the anterior, or motor roots
possessed a certain degree of sensibility, though not so
acute as in the posterior roots. Here is met a curious event
in the history of the recurrent sensibility: Magendie's ex-
periments, being in a manner opposed to the views of Bell,
which were then universally received, attracted consider-
able notice; but when, after 1839, he attempted to repeat
them, he utterly failed, and finally abandoned the ground
that he had taken — one of the many examples of the hon-
esty of description which mark the experiments of this dis-
tinguished physiologist. It was not until 1846 that Ber-
nard revived " recurrent sensibility " and succeeded in
again demonstrating it. He remembered that in 1839 the
experiments for the lectures of Magendie were prepared in
the morning, and that the animals used for the purpose of
demonstrating recurrent sensibility were thus permitted a
period of repose before demonstrations were made during
the lecture, which took place in the afternoon. He himself
had made operations on the spinal cord and roots of the

RECURRENT SENSIBILITY 31

nerves, and had found that after the operation of opening
the spinal canal, which is exceedingly painful and tedious,
the general sensibility of the animal was blunted. The
state of the nerves, then, was more natural after the animal
had been permitted to recover from the first effects of the
operation than immediately after the exposure of the roots.
Carrying this idea into practice, he opened the spinal canal
in dogs and allowed them two or three hours' repose before
he made his observations on the roots of the nerves. In
experiments conducted in this way, especially in dogs that
were vigorous and well nourished, he always found the an-
terior roots of the nerves sensitive. He found, also, that
the sensibility was derived from the posterior roots; for the
division of these immediately abolished the sensibility of
the anterior roots. He made in addition some interesting
observations upon the disappearance of sensibility from ex-
haustion, anesthetics and other causes. He showed that
sensibility first disappeared in the anterior roots, then in
the periphery and last in the posterior roots. When the
sensibility reappeared, it was first manifest in the posterior
roots, then in the periphery and last in the anterior roots.
These experiments of Bernard have fully established the
fact of recurrent sensibility; but so far as I am aware, they
have been repeated and confirmed only by Schiff.

As I have lately had occasion to repeat these experi-
ments at the New Orleans School of Medicine and to
demonstrate to the class, in my regular course of lectures,
recurrent sensibility, I have thought the subject sufficient-
ly interesting to put upon record my own experiments
which confirm the view held by Magendie, in 1839,
afterward abandoned by him but confirmed in 1846 by
Bernard.

Bernard's experiments were made before the use of
ether as an anesthetic; but Schiff, who repeated these ex-
periments at a later date, always made use of ether in the
operation of opening the spinal canal. This of course
abolishes pain during the preliminary operation; and in the
course of one or two hours the animal entirely recovers
from its effects and is ready for the observations on the
nerve-roots. It is best to select a vigorous healthy dog
for the operation as the sensibility is then much more
marked. The most convenient situation, also, at which to

32 RECURRENT SENSIBILITY

ojicn the spinal canal is in the Inmbar rci^ion at the point
of junction of the iliac bones with the spinal column.

Experiment I. — February 15, 1861, 11 a.m. A vigorous me-
dium-sized dog was completely etherized, placed on his belly on the
table, with a billet of wood under the lumbar region to make this
part of the spinal column prominent. The hair was then cut from
the i)arts to be incised, and a longitudinal incision about four inches
in length was made just to the left of the spinous processes of the
lower lumbar vertebrae. This incision was then carried down by
the sides of the spinous processes to their junction witb the laminae.
The lamin.-e of the fifth, sixth and seventh lumbar vertebra; were
then denuded of their muscles and were cut through vertically by
a fine saw carried as near the spinous processes as possible. The
laminre were then divided near the transverse processes, by a cut
of the saw parallel to the first but directed obliquely inward. There
is danger in making this second cut of wounding the nerves as they
emerge from the spinal canal and also of opening the vertebral
sinus; but this may be avoided by cutting wath great care, not going
through the lamin?e entirely but breaking them off by prying with
a chisel introduced into the cut next the spinous processes. In
opening the spinal canal the roots of the fifth pair of lumbar nerves
were divided. The roots of the ixth pair, however, were intact.
These roots were separated carefully by a delicate blunt hook,
threads were passed beneath them, the wound was closed by su-
tures and the animal set at liberty. After recovering from the
effects of the ether, it was discovered that his left posterior ex-
tremity was partially, though not completely paralyzed, owing to
the injury to the nerves during the operation of opening the spinal
canal.

February 16, 11 a.m. Twenty- four hours after the operation
the wound was opened; the discharges, which had been consider-
able, were removed, and irritation by means of pinching with for-
ceps was applied to the roots of the nerves. Both roots were sen-
sitive, as manifested by the cries of the animal, but the sensibility
of the posterior root was by far the more acute.

The wound was then again closed and the same experiments
were made before the medical class, at 2 p. m. The sensibility
of the posterior root was then acute; but the sensibility of the an-
terior root had considerably diminished, probably on account of
exhaustion produced by the experiment at 11 a. m.

Experiment II. — February 16, 11.30 a.m. The dog used in
this experiment was a larger, younger and more vigorous dog
than the one used in Experiment I. The animal was etherized and
the incisions made, denuding the spinous processes and laminae of
the sixth and seventh lumbar vertebrae, as in Experiment I, with
the difference that the operation was made on the right side. The
laminae of the sixth and seventh lumbar vertebrae were then re-
moved W'ithout wounding the roots of any of the nerves. This was
done by makmg the cut witb the saw farthest from the spinous
processes extend only partially through the bone and then removing

RECURRENT SENSIBILITY 33

the laminae by prying them off with a chisel. The roots of the
sixth lumbar nerves were then isolated, and threads of fine silk
were passed beneath them. The wound was then closed and the
animal set at liberty. The operation lasted about three quarters
of an hour.

2 p. M. The animal was exhibited to the medical class and
the following observations were made. The slightest touch of the
posterior root produced intense pain manifested by cries. Upon
pinching the anterior root, the animal cried, evidently suffer-
ing pain though not so intensely as when the posterior root was
barely touched. Care was taken in irritating the anterior root not
to touch the posterior root. The posterior root was then divided,
its section causing intense pain, and the anterior root was again
irritated. Now, however, its sensibility had entirely disappeared,
and it could be contused in the roughest manner without producing
any evidence of suffering.

The operation for the purpose of exposing the spinal
cord is quite difficult and tedious, on account of hemor-
rhage, which is sometimes abundant, and difficulty in avoid-
ing injury of the roots of the nerves and opening the ver-
tebral sinus. These accidents can be avoided, however,
with a little practice. The instruments necessary for open-
ing the spinal canal are a small saw, a Hey's saw, a pair of
small bone-nippers and a chisel. When the laminae of the
vertebrae have been removed, the spinal cord is exposed,
surrounded by a certain quantity of fat which should be
carefully removed with forceps. A pair of small blunt
hooks are then necessary for the purpose of isolating and
catching up the roots of the nerves. It is best then to
pass a fine thread under the nerves before closing the
wound, so as to be able easily to find them again. The
wound is then to be closed and the animal allowed to
repose for two or three hours, when it will have re-
covered entirely from the effects of the operation and the
roots of the nerves will have regained their normal sen-
sibility.

I have thus detailed two experiments which show in a
marked manner, especially Experiment II, that the anterior
roots of the spinal nerves are not exclusively motor but
that they possess a certain degree of sensibility; that this
sensibility is recurrent and is derived from the posterior, or
sensory roots; and that after the division of these roots, it
is immediately lost. In this I have confirmed the experi-
ments of Magendie, in 1822 and 1839, experiments which
3

34 RECURRENT SENSIBILITY

he failed to repeat with success after that date, which were
repeated in 1846 by Bernard, and later still by Schiff, but
have never been repeated, so far as I am aware, ni England
or this country. In these experiments I have attempted
to show nothing beyond the recurrent sensibility and its
derivation from the posterior, or sensory roots.

IV

HISTORICAL CONSIDERATIONS CONCERNING
THE PROPERTIES OF THE ROOTS OF THE
SPINAL NERVES

Published in the " Quarterly Journal of Psychological Medicine " for October,

1868.

At the time when the functions of the nerves given off
from the spinal cord began to be understood by physiolo-
gists, there was much discussion in regard to the claims
of different observers to the honor of the discovery of the
different properties of their anterior and posterior roots.
Alexander Walker,* Sir Charles Bell f and Herbert jNIayo.:}:
in England, all claimed a share, more or less considerable,
in this great discovery: and in France. Magendie * pro-
fessed to have been the first to demonstrate this important
fact by direct experiment.

* Walker, " The Nervous System, anatomical and physiological : in which
the functions of the various parts of the brain are for the first time assigned,
and to which is prefixed some account of the author's earliest discoveries, of
which the more recent doctrine of Bell, Magendie, etc., is shown to be at
once a plagiarism, an inversion, and a blunder, associated with useless experi-
ments, which they have neither understood nor explained." London, 1S44,
p. 50, et seq.

f Bell, " The Nervous System of the Human Body : as explained in a
series of papers read before the Royal Society of London." London, 1844,
p. 13, et seq.

Shaw, " Narrative of the Discoveries of Sir Charles Bell in the Nervous
System." London, 1839.

X Mayo, " Outlines of Human Physiolog}'." London, 1827, p. 240.

* Magendie, " Experiences sur les fonctions des racines des nerfs rachi-
diens," — Journal de physiologie. Paris, 1822, tome ii., p. 276 ; et " Expe-
riences sur les fonctions des racines des nerfs qui naissent de la moelle epinere."
Ibid., p. 366.

Magendie et Desmoulins, " Anatomic des syst^mes nerveux des animaux
a vertebres." Paris, 1825, tome ii., p. 777.

Magendie, " Precis elementaire de physiologie." Deuxieme edition.
Paris, 1825, tome i., pp. 167 and 216.

" Note additionelle aux deuxieme memoire sur les nerfs de la

face," — Journal de physiologie. Paris, 1830, tome x., p. 189.

" Le9ons sur les fonctions et les maladies du systeme nerveux."

Paris, 1 841, tome i., p. 64.

35

36 ROOTS OF THE SPINAL NERVES

The pretensions of Walker and of Mayo are easily dis-
posed of. Walker, who was undoubtedly the first to dis-
tinctly state, in 1809, that one of the roots of the nerves was
for sensation, while the other presided over movements,
did not support his theory by any facts or experiments and
was led into the error of supposing that the anterior roots
were sensitive and the posterior were motor, precisely the
reverse of what was proved to be the case by the subsequent
experiments of Magendie. Walker, in his work, ridicules
the idea of studying the functions of the body by experi-
ments on living animals; yet he details an experiment, " the
only operation on a living animal which he ever has per-
formed, or ever will perform," in which he exposed the
roots of the spinal nerves in a frog and found " that irri-
tation of the anterior roots caused motion, and irritation
of the posterior caused little or none." * Inasmuch as
Walker claimed in his publications, as late as 1844, that he
had always considered the posterior roots as motor and the
anterior as sensitive, it does not seem that he has any well-
founded title to the discovery of the real pro])erties of these
nerves. The claims of Mayo are even more indefinite. He
simply states, long after the publication of the experiments
of Magendie, that " the remarkable analogy which exists
between the fifth nerve and the spinal nerves, led me to
suppose that the two roots of the spinal nerves had the
same discrepancy of function with the two roots of the
fifth; and that the ganglionic portion might belong to sen-
sation, the smaller anterior portion to volition." f

All discussion, therefore, relative to priority in the dis-
covery of the true functions of the roots of the nerves is
confined to the claims of Bell and of Magendie. The ex-
periments of Midler :|: and others were all made after 1822,
the date of the first publication of the experiments of Ma-
gendie in the " Journal de physiologic."

In nearly every treatise on physiology published since
1822 and in almost all w^orks on the nervous system subse-
quent to that date, the great discovery of the distinct seat
of motion and sensation in the spinal nerves is ascribed to

* Walker, Oj>. a'(., p. i8. \ Mayo, Loc. cit.

% Mliller, " Physiologic du systeme nerveux." Paris, 1840, tome i., p.
85, et seq. ; and " Manuel de physiologie," Paris, 1851, tome i., p. 598, et seq.
The experiments of Miiller were first published in 1831.

ROOTS OF THE SPINAL NERVES 37

Sir Charles Bell. The name of Magendie is seldom men-
tioned in this connection, even in France; and his discov-
eries are supposed to relate chiefly to the seat of sensation
and motion in the different columns of the spinal cord.

Before discussing the real claims of Bell and Magendie,
it may not be uninteresting to review the statements in
some of the more common works by English, German
and French authors. Todd and Bowman * say that " it
can not be denied that the endowment of the roots was dis-
covered by Bell; " Carpenter f says " that the merit of this
discovery is almost entirely due to Sir Charles Bell;"
Kirkes :{: makes the same statement; Bostock * associates
the names of Bell and Magendie but says that the experi-
ments of Bell were clearly antecedent to those of Magen-
die; but Elliotson.il who had evidently consulted carefully
the literature of the subject, distinctly asserts that Bell had
no idea that the anterior roots of the spinal nerves were
motor and the posterior roots sensory, before the publica-
tion of Magendie's experiments in 1822; and he ascribes
the whole honor of the discovery to Magendie. So far as
I am aware, Elliotson is the only English writer, except
Walker and Mayo, who themselves laid claim to the dis-
covery, who does not ascribe the whole honor to Bell.^

In all the German works which I have examined, the
credit of the discovery is given to Bell. Reference has
already been made to the work of Miiller on the nervous
system, 0 and his manual of physiology. 1^ The discovery is
also unreservedly ascribed to Bell by Valentin,^ by Volk-
mann I and by Budge.**

* Todd and Bowman, " The Physiological Anatomy and Physiology of
Man." Philadelphia, 1857, p. 274.

f Carpenter, " Principles of Human Physiology." Philadelphia, 1853, p. 651.
i Kirkes, " Manual of Physiology." Philadelphia, 1857, p. 327.

* Bostock, "An Elementary System of Physiology." London, 1824, vol.
i., p. 281.

II Elliotson, " Human Physiology." London, 1840, p. 465.

^ I should also except the author of a review in the " London Medical
and Physical Journal " for 1829. This review will be referred to hereafter.

^ Op. a'L, p. 85.

t Op. cit., p. 598.

% Valentin, " Lehrbuch der Physiologie des Menschen." Braunschweig,
1844, Band ii., S. 627.

I Volkmann, in " Wagner's Handworterbuch der Physiologie." Braun-
schweig, 1S44, Band ii., S. 558.

** Budge, " Lehrbuch der Speciellen Physiologie des Menschen." Leipzig,
1862, S. 623.

38 ROOTS OF THE SPINAL NERVES

The most interesting bibliographical researches on this
subject are in connection with the French treatises on phys-
iology and on the nervous system. In 1816 Magendie
published his " Precis elementaire de physiologic," which,
in its arrangement and the general method of considering
the subject, has served as the model of the best works on
physiology which have appeared since that date. In his
various publications already referred to, and in the second
edition of the " Precis elementaire," published in 1825, as
well as in subsequent editions of the same work, Magendie
formally lays claim to the credit of the discovery of the
functions of the roots of the nerves; and in the " Journal de
physiologic " * he gives full credit to Sir Charles Bell for
his observations, quoting, in the original, the account of
the only experiment performed by Bell; and yet, with one
or two exceptions, all the French works which treat of the
subject seem to regard Sir Charles Bell as the real discover-
er. The author to whom I particularly refer as the excep-
tion is Vulpian, who has lately published a very interesting
work on the nervous system. Vulpian does not distinctly
state that he has consulted the original memoir printed by
Bell in 181 1, but he seems to appreciate so fully the state
of the question that the present review would have been
rendered unnecessary had I not been enabled to produce
an exact reprint of the original memoir f (of the existence
of which Vulpian does not seem to be aware), and from this
to confirm fully the statements in regard to the priority
in this great discovery. Vulpian :|: recognizes fully the in-
justice which Magendie has so long received, and exposes,
also, the unwarrantable alterations wdiich Bell has made in
a paper originally published in the " Philosophical Trans-
actions " in 1 82 1, and reprinted subsequently in 1844.* In
the reprint of this paper Bell has not hesitated to so modify
his language as to make his remarks correspond with the
facts discovered by Magendie in 1822, giving to the reader
the impression that he held these opinions as early as 1821.

* Tome X., p. 370.

•f " Documents and Dates of Modern Discoveries in the Nervous System."
London, John Churchill, 1839, p. 37, et seq.

\ Vulpian, " Le9ons sur la physiologic generale et comparee du systeme
nerveux." Paris, 1866, pp. 109 et 127.

* Bell, " The Nervous System of the Human Body : as explained in a series
of papers read before the Royal Society of London." London, 1844, p. 33.

ROOTS OF THE SPINAL NERVES 39

Longet in his work on the nervous system says: " We
see that, without having absohitely demonstrated it, Ch.
Bell suspected that the role of the posterior roots relates
to sensibility." * In this work Longet quotes from Bell's
memoir of 181 1 reprinted in the " Documents and Dates
of Modern Discoveries in the Nervous System." The same
passage occurs in Longet's " Traite de physiologic," but
the quotations are here made from the English and the
French editions of the work of Mr. Shaw.f Among the
other French authors who ascribe the discovery of the prop-
erties of the roots of the spinal nerves to Ch. Bell, may be
mentioned Beclard,:j: Flourens,* Foville || and Gratiolet.^
All of these authors, with enthusiasm, ascribe to Charles
Bell the great discovery which I shall show belongs to
Magendie.

REVIEW OF THE CLAIMS OF SIR CHARLES BELL TO THE
DISCOVERY OF THE PROPERTIES OF THE ROOTS OF THE
SPINAL NERVES, AS SHOWN BY HIS WRITINGS, AND BY
THE NARRATIVE OF HIS DISCOVERIES, BY MR. SHAW

The original memoir by Sir Charles Bell, entitled " Idea
of a New Anatomy of the Brain," which was printed in
1811,0 is now almost inaccessible. It was printed for
private distribution and it is said that the number of copies

* Longet, " Anatomic et physiologic du systeme nerveux de ''homme at des
animaux vertebres." Paris, 1832, tome i., p. 28.

f Longet, " Traite de physiologic. " Paris, i860, p. 172.

:]: Beclard, " Traite elementaire de physiologic humainc." Paris, 1859,

* Flourens, " Rccherchcs experimentales sur Ics proprietes et Ics fonc-
tions du systeme nerveux dans Ics animaux vertebres." Paris, 1842, p. 13.
Flourens, in his Memoir of Magendie read at the Academy of Sciences, soon
after the death of this great physiologist, in 1S55, again ascribes the credit of
the discovery of the different properties of the roots of the spinal nerves to
Charles Bell. A translation of this memoir is published in the Smithsonian
Report for 1866, p. gi, et seq.

II Foville, " Tr«ite complct de I'anatomie, de la physiologic ct de la
pathologic du systeme nerveux cerebro- spinal (i^re partie) anatomic." Paris,
1S44, p. 493.

"^ Lcuret et Gratiolet, " Anatomic comparec du systeme nerveux considere
dans ses rapports avec rintelligencc." Paris, 1839-1857, tome ii , p. 330.

^ In a paper read before the Medico-Chirurgical Society, in April, 1822,
Mr. J. Shaw gives the date of the first paper by Charles Bell as 1809. This
error is quoted into many reviews and other publications, but it has been cor-
rected by Bell himself and by Mr. Shaw. (Alexander Shaw's " Narrative of the
Discoveries of Sir Charles Bell in the Nervous System," London, 1830, p. 14.)

40 ROOTS OF THE SPINAL NERVES

was only one hundred.* From the writings of various au-
thors who have discussed the claims of Bell and of Magen-
die, it appears that few have had the opportunity of con-
sulting the original paper. It is, of course, frequently re-
ferred to by Bell himself, and by Mr. Shaw, his brother-in-
law. Magendie speaks of having obtained a copy of this
work and gives a quotation from it in the " Journal de
physiologie," f Miiller refers to the original paper but
does not definitely state that he has had the opportunity
of consulting'it.ij; In a review published in the " London
Medical and Physical Journal " in 1829, it is distinctly
stated that the original paper was consulted;** and in a
reply to this review by a pupil of Charles Bell, published
in the same Journal, in 1830, reference is again made. to
the original tract. || A later writer in the " British and
Foreign Medico-Chirurgical Review " assumes to have
compared the reprint, already referred to, with the orig-
inal paper.'^ With these exceptions, no author, so far
as I know, has consulted the original document ; and
the claims of Charles Bell to the discovery are based
upon quotations from the pamphlet of 181 1, made by
himself and by Mr. Shaw, which have been copied into
nearly all works treating of the physiology of the nervous
system. Writers on this subject have thus been forced to
get their ideas of the claims of Charles Bell from his later
publications, particularly his work on the nervous system,^
which has been very . widely circulated and has passed
through several editions. I have before me a w^ork, appar-
ently very little known, entitled " Documents and Dates
of Modern Discoveries in the Nervous System," published
in London, in 1839, by John Churchill. This volume con-
tains a reprint of the original paper of Charles Bell, entire.
So far as I have been able to compare this reprint with the

* Vulpian, " Le9ons sur la physiologie generale et comparee du syst^me
nerveux," Paris, 1866, p. 109.

f Op. cit., tome ii., p. 370.

\ Miiller, " Physiologie du systeme nerveux," Paris, 1840, tome i., p. 85.

* " The London Medical and Physical Journal," 1829, vol. Ixii., p. 525.

II Ibid., 1830, vol. Ixiii., p. 40. This writer refers to the tract as printed
in i8og.

•^ " The British and Foreign Medico-Chirurgical Review," London, 1840,
vol. ix., p. 98.

0 Bell, " The Nervous System of the Human Body," third edition, London^
1844.

ROOTS OF THE SPINAL NERVES 41

quotations from the original by Bell and by Shaw, it has
proved to be entirely accurate. Its accuracy is also attested
by the writer in the " Medico-Chirurgical Review," already
referred to. It does not appear that this volume is referred
to by any physiological writers except Longet;* and it is
a matter of surprise that this distinguished author, if he
has carefully read the memoir of Charles Bell, can refrain
from giving to Magendie full credit for his brilliant discov-
ery. In his work on physiology, f Longet quotes the paper
of Bell from the " Narrative " of Mr. Shaw, and says noth-
ing about the '* Documents and Dates." It is all the more
surprising that the claims of Magendie should not be rec-
ognized in France, when an English writer, Elliotson, had
already rendered him full justice, which was also given him,
in 1829, by a reviewer in the " London Medical and Phys-
ical Journal," the author of the review here attributing
" this great discovery entirely to Magendie." X

With all the publications by Bell and Magendie before
us, it would seem that now, when the acrimony of contro-
versy has subsided, we should be able to settle the claims
of each of these physiologists to the discovery under consid-
eration. I shall abstain from reviewing the discussions of
this question which took place soon after the publication
of Magendie's experiments, and proceed to study carefully
the various publications on this subject, by Bell and Ma-
gendie, beginning with the memoir printed in 181 1.

VIEWS OF SIR CHARLES BELL, IN 181I, CONCERNING THE
PROPERTIES OF THE ROOTS OF THE SPINAL NERVES,
TAKEN FROM HIS " IDEA OF A NEW ANATOMY OF THE
BRAIN "

Almost all the quotations which I shall make from this
remarkable pamphlet are to be found in Shaw's " Narra-
tive " of Bell's discoveries, a work which is sufTficiently
common and accessible and which certainly presents the
claims of Bell in the most favorable light possible. I refer

* Longet, " Anatomic et physiologic du systeme nerveux de rhomme et
des animaux vertebres," Paris, 1842, tome i., p. 27.

This reprint of Bell's original memoir is distinctly referred to by Bernard in
his " Rapport sur le progr^s et la marche de la physiologic generale en France,"
Paris, 1867, p. 155, which has appeared since this review was written.

+ Longet, " Traite de physiologic," Paris, i860, tome ii., p. 172.

I Zoc. cit., p. 532.

42 ROOTS OF THE SPINAL NERVES

the reader to this work to show that nothing is omitted in
the following quotations which has an important bearing
on the subject under consideration.

After a short notice of the then prevailing opinions con-
cerning the structure and functions of the nerves and the
encephalon, Bell proceeds to give a general statement of
his views, as follows:

" In opposition to these opinions, I have to offer reasons for be-
lieving that the cerebrum and cerebellum are different in function
as in form ; that the parts of the cerebrum have different functions ;
and that the nerves which we trace in the body are not single nerves
possessing various powers, but bundles of different nerves, whose
filaments are united for convenience of distribution, but which are
distinct in office, as they are in origin, from the brain.

" That the external organs of the senses have the matter of the
nerves adapted to receive certain impressions, while the correspond-
ing organs of the brain are put in activity by other external excite-
ment. That the idea or perception is according to the part of the
brain to which the nerve is attached, and that each organ has a
certain limited number of changes to be wrought upon it by the
external impression.

" That the nerves of sense, the nerves of motion, and the vital
nerves, are distinct through their whole course, though they seem
sometimes united in one bundle; and that they depend for their
attributes on the organs of the brain to which they are severally
attached.

" The view which I have to present will serve to show why
there are divisions, and many distinct parts in the brain ; why some
nerves are simple in their origin and distribution, and others intri-
cate beyond description. It will explain the apparently accidental
connection between the twigs of nerves. It will do away with the
difficulty of conceiving how sensation and volition should be the
operation of the same nerve at the same moment. It will show how
a nerve may lose one property and retain another; and it will give
an interest to the labors of the anatomist in tracing the nerves " —
(pp. 39, 40).

This extract simply shows that Bell entertained the
opinion prevalent at that day, that all the nerves derived
their properties from the encephalon. The new idea which
he advances is, that the nerves are to be divided into nerves
of motioti, nerves of sensation and vital nerves, which last
were at that time supposed to be the nerves which pre-
sided over the organic functions. The theoretical division
of the nervous fibres into motor and sensory had been made
by Alexander Walker in 1809; '^ and Willis held the opin-

* Loc. cit.

ROOTS OF THE SPINAL NERVES 43

ion that the cerebellum, from which Bell supposed that the
" vital nerves " were derived, presided over the functions
of organic life. These ideas, therefore, cannot be claimed
as original.

After some general considerations concerning the struc-
ture and probable function of different parts of the nervous
system, the following experiments are detailed:

" In thinking of this subject, it is natural to expect that we
should be able to put the matter to proof by experiment. But how
is this to be accomplished, since any experiment direct upon the
brain itself must be difficult, if not impossible? I took this view
of the subject. The medulla spinalis has a central division, and also
a distinction into anterior and posterior fasciculi, corresponding
with the anterior and posterior portions of the brain. Further,
we can trace down the crura of the cerebrum into the anterior
fasciculus of the spinal marrow, and the crura of the cerebellum
into the posterior fasciculus. I thought that here I might have
an opportunity of touching the cerebellum, as it were, through the
posterior portion of the spinal marrow, and the cerebrum by the
anterior portion. To this end I made experiments, which, though
they were not conclusive, encouraged me in the view I had taken.

" I found that injury done to the anterior portion of the spinal
marrow convulsed the animal more certainly than injury done to
the posterior portion ; but I found it difficult to make the experi-
ment without injuring both portions.

" Next, considering that the spinal nerves have a double root,
and being of opinion that the properties of the nerves are derived
from their connections with the parts of the brain, I thought I had
an opportunity of putting my opinion to the test of experiment, and
of proving at the same time that nerves of different endowments
were in the same cord, and held together by the same sheath.

" On laying bare the roots of the spinal nerves, I found that I
could cut across the posterior fasciculus of nerves, which took its
origin from the posterior portion of the spinal marrow, without
convulsing the muscles of the back; but that on touching the ante-
rior fasciculus with the point of the knife, the muscles of the back
were immediately convulsed. Such were my reasons for conclud-
ing that the cerebrum and the cerebellum were parts distinct in
function, and that every nerve possessing a double function ob-
tained that by having a double root. I now saw the meaning of the
double connection of the nerves with the spinal marrow ; and also
the cause of that seeming intricacy in the connections of the nerves
throughout their course, which were not double in their origin.

" The spinal nerves being double, and having their roots in the
spinal marrow, of which a portion comes from the cerebrum and a
portion from the cerebellum, they convey the attributes of both
grand divisions of the brain to every part; and therefore the dis-
tribution of such nerves is simple, one nerve supplying its distinct
part"— (pp. 50-52).

44 ROOTS OF THE SPINAL NERVES

The above quotation embodies all the experiments de-
tailed by Bell in his first essay. From the account of these
experiments given by Vulpian, it would not seem that he
had consulted the orignal work. Vuli)ian speaks of the first
experiment on the spinal cord as performed upon a rabbit
recently killed. No such statement is made in the original.
He also speaks of the experiment upon the roots of the
nerves as made upon a living animal.* This does not
appear in the original. On the contrary, Bell speaks
of cutting across the posterior roots (p. 51) without
"convulsing the muscles of the back," and has nothing
to say about the sensibility, which certainly would have
been manifested if the operation had been performed on
a living animal.

A careful review of the last quotation, which is alsO'
made in full by Shaw, will give a clear idea of the real opin-
ion of Bell concerning the different properties of the roots
of the nerves. He evidently regards the anterior fasciculi
of the cord as prolongations of the crura cerebri; and the
posterior fasciculi as prolongations of the crura cerebelli;
and he found that injury to the anterior portion of the cord
produced convulsions " more certainly " than injury done
to the posterior portion. He next assumes that the double-
roots of the spinal nerves receive their properties from their
connections with different parts of the brain (the cerebrum
and cerebellum); and his experiments on the roots of the
nerves agreeing in every respect with the experiments upon
the anterior and posterior fasciculi of the cord, he concludes
that the cerebrum and cerebellum, and consequently the
different roots of the spinal nerves, are parts distinct in
function.

It remains now to see what distinct functions are as-
cribed to the cerebrum and cerebellum, and consequently
to the nerves proceeding from these parts. This is clearly
indicated in the following quotation:

" The cerebellum, when compared with the cerebrum, is sim-
ple in its form. It has no internal tubercles or masses of cineritious
matter in it. The medullary matter comes down from the cineritious
cortex, and forms the crus ; and the crus runs into union with the
same process from the cerebrum ; and they together form the me-
dulla spinalis, and are continued down into the spinal marrow;

* Vulpian, Op. cit., p. iii.

ROOTS OF THE SPINAL NERVES 45

and these crura or processes afford double origin to the double
nerves of the spine. The nerves proceeding from the crus cere-
belli go everywhere (in seeming union with those from the crus
cerebri) ; they unite the body together, and control the actions of
the bodily frame ; and especially govern the operation of the vis-
cera necessary to the continuance of life.*

" In all animals having a nervous system, the cerebellum is
apparent, even though there be no cerebrum. The cerebrum is seen
in such tribes of animals as have organs of sense, and it is seen
to be near the eyes, a principal organ of sense; and sometimes it
is quite separate from the cerebellum.

" The cerebrum I consider as the grand organ by which the
mind is united to the body. Into it all the nerves from the external
•organs of the senses enter; and from it all the nerves which are
agents of the will pass out" — (pp. 53, 54).

The above quotations complete the history of Sir
Charles Bell's ideas in regard to the functions of the roots
of the nerves. The posterior roots are supposed to
" unite the body together, and control the actions of the
bodily frame; and especially govern the operation of the
viscera necessary to the continuance of life." The anterior
roots convey to the cerebrum impressions " from the ex-
ternal organs of the senses," and are the nerves by which
the agents of the will pass out. It is true that the language
is not very clear or strictly scientific according to our
present ideas, but it must be evident to every one that Bell
regarded the anterior roots as nerves of both motion and
sensation, and the posterior roots as the so-called " vital "
nerves. Indeed, Mr. Alexander Shaw, the most enthusi-
astic and persistent partisan of Bell, admits the uncertainty
of Bell's statements concerning the seat of sensation in the
nervous roots in the following passage: " Accordingly, that
it is left in doubt by Sir Charles Bell, when he composed his
■* Essay on the Brain ' in 181 1, whether the power of giving
sensation belonged to the posterior root, must be admit-
ted." f The quotation made above, which was omitted by
Mr. Shaw, shows that this statement is not strictly correct.
The question of sensibility of the posterior roots was not

* This important paragraph, in which the functions of the posterior roots of
the nerves (" the nerves proceeding from the crus cerebelli ") are distinctly
assigned without a mention of any sensory property, is not quoted by Shaw ;
and this passage, which is nowhere contradicted, makes it evident that Bell
knew nothing and discovered nothing of the properties of the sensory roots.

f Shaw, " Narrative of the Discoveries of Sir Charles Bell in the Nervous
System." London, 1839, P- 4^-

46 ROOTS OF THE SPINAL NERVES

mentioned by Bell; and, far from being " left in doubt," an-
other function was assigned.

The following quotation from Bell's work reiterates the
supposed functions of the roots:

" The convex bodies, which are seated in the lower part of the
cerebrum, and into which the nerves of sense enter, have extensive
connection with the hemispheres on their upper part. From the
nieduHary matter of the hemispheres, again, there pass down, con-
verging to the crura, striae, which is the medullary matter, taking
upon it the character of a nerve ; for, from the crura cerebri, or its
prolongation in the anterior fasciculi of the spinal marrow, go off
the nerves of motion.

" But with these nerves of motion, which are passing outward,
there are nerves going inward ; nerves from the surfaces of the
body; nerves of touch; and nerves of peculiar sensibility, having
their seat in the body or viscera. It is not improbable that the
tracts of cineritious matter which we observe in the course of the
medullary matter of the brain, are the seat of such peculiar sensibili-
ties; the organs of certain powers which seem resident in the body "
— (PP- 55. 56)-

The above passage leaves no doubt that Bell thought
that the nerves of motion, going off from the anterior fas-
ciculi of the spinal marrow, contained filaments of sensation
in the same sheath.

The last paragraph of the original memoir, which ap-
parently contains the conclusions drawn by its author from
his facts and experiments, should never have been omitted
in quotations intended to give a correct idea of the views
of Sir Charles Bell, as exemplified by this remarkable
pamphlet. This, however, is not quoted by Mr. Shaw, or,,
so far as I can ascertain, by any other writer. This para-
graph needs no comment, as it presents the views of the au-
thor more clearly than any other passage:

" From the cineritious matter, which is chiefly external, and
forming the surface of the cerebrum ; and from the grand centre
of the medullary matter of the cerebrum, what are called the
crura descend. These are fasciculated processes of the cerebrum,
from which go off the nerves of motion, the nerves governing the
muscular frame. Through the nerves of sense the sensorium re-
ceives impressions, but the will is expressed through the medium
of the nerves of motion. The secret operations of the bodily frame,
and the connections which unite the parts of the body into a sys-
tem, are through the cerebellum and the nerves proceeding from
it"— (p. 60).

It is not pretended that Charles Bell made any publica-
tion concerning the functions of the roots of the spinal

ROOTS OF THE SPINAL NERVES 47

nerves between 181 1 and 1821, when he read before the
"Royal Society of London" a paper "On the nerves;
giving an account of some experiments on their structure
and functions, which lead to a new arrangement of the sys-
tem." In this article, as it is printed in the " Philosophical
Transactions," 182 1, Part I., p. 398, ct scq., there is no
indication that the author was aware of the true properties
of the anterior and posterior roots. The claims of Bell to
this discovery, then, rest entirely on the unpublished
pamphlet of 181 1; and the extracts I have given show con-
clusively that he attributed to the posterior roots proper-
ties w^hich they do not possess, and gave to the anterior
roots the properties both of motion and sensation.

The state of the question in 181 1 may, then, be
summed up in a very few words:

In 1809, Alexander Walker proposed the theory- that
one of the roots of the spinal nerves was for motion and
the other for sensation. This was done on purely theoret-
ical grounds; and Walker erred in supposing that the pos-
terior roots were motor and the anterior sensory.*

In 181 1, Sir Charles Bell advanced the views which I
have already fully given; and to him is due the credit of
having been the first to attempt to verify his theories by

* Walker states his theory of the distinct functions of the roots of the nerve
in the following words :

" Thus, then, it is proven to us, that medullary action commences in the
organs of sense ; passes, in a general manner, to the spinal marrow, by the an-
terior fascicula of the spinal nerv'es, which are, therefore, nerves of sensation,
and the connections of which with the spinal marrow or brain must be termed
their spinal or cerebral terminations ; ascends through the anterior columns of
the spinal marrow, which are, therefore, its ascending columns ; passes forward
through the inferior fasciculi of the medulla oblongata, and then through the
crura cerebri ; extends forward, outward, and upward through the corpora
striata ; and reaches the hemispheres of the cerebrum itself. This precisely is
the course of its ascent to the sensorium commune.

" From the posterior part of the medulla of the hemispheres, it returns by
the thalami, passing backward, inward, and downward ; flows backward in the
fasciculi under the nates and testes ; backward and upward through the pro-
cesses cerebelli ad testes or anterior peduncles of the cerebellum ; and thus
reaches the medulla of the cerebellum itself.

" From the cerebellum it descends through the posterior columns of the
spinal marrow, which are, therefore, its descending columns ; and expands
through the posterior fasciculi of all the nerves, which are, therefore, the nerves
of volition, and the connection of which with the spinal marrow or brain must
be termed their spinal or cerebellic origins. This precisely is the course of its
descent from the sensorium commune toward the muscular system." — (" Docu-
ments and Dates of Modern Discoveries in the Nervous System." London,
1839, p. 36.)

48 ROOTS OF THE SPINAL NERVES

experiments. He was iin(loiil:)te(lly the first to operate upon
the roots of the spinal nerves in an animal recently killed;
but he was far from attributing to each root its proper func-
tion, which was done by Magendie in 1822.

REVIEW OF THE WRITINGS OF SIR CHARLES BALL SUBSE-
QUENT TO 181 I, IN WHICH IT IS IMPLIED THAT HE DIS-
COVERED THE FUNCTIONS OF THE ROOTS OF THE SPINAL
NERVES

All the credit which I have to give to Sir Charles Bell
for advances in the anatomy and physiology of the spinal
nerves must cease with the review of the pamphlet of 181 1.
In a memoir on the nerves of the head, read before the
" Royal Society," July 12, 1821, more than a year before
the publication of the experiments of Magendie, there is
no mention of distinct motor and sensory roots of the
spinal nerves or of distinct properties in different portions
of the spinal cord. This paper was republished by Bell,
after the publication of Magendie's observations, in a work
on the nervous system; and it is this republication which is
most accessible and most frequently referred to by physio-
logical writers. The republication avowedly contains
" some additional explanations; " but a careful comparison
of it with the original shows that every portion of it that
was susceptible of such verbal alteration has been modi-
fied to make it correspond with the discovery, by Magen-
die. But at the same time, the impression received by the
reader is that it is essentially the same as the memoir pub-
lished in 1 82 1. These alterations have been commented
upon by Vulpian; but I propose to give some extracts from
the two papers, side by side, showing how the unwarrant-
able verbal alterations in the reprint are calculated to give
the impression that Bell was fully aware of the true seat of
motion and sensation in the spinal cord and the spinal
nerves, and had succeeded, by applying the same mode of
investigation to the nerves of the brain, in demonstrating
" that the principle in question held good equally with re-
gard to them as with regard to the spinal nerves." *

* " This is claimed for Bell by his brother-in-law, Mr. Alexander Shaw, from
whom the above passage in quotation marks is taken." — (Shaw, " Narrative of
the Discoveries of Charles Bell in the Nervous System." London, 1839, p. 8.)

ROOTS OF THE SPINAL NERVES

49

EXTRACTS FROM THE MEMOIRS OF SIR CHARLES BELL, PUB-
LISHED IN THE PHILOSOPHICAL TRANSACTIONS AND IN
HIS WORK ON THE NERVOUS SYSTEM *

On the nerves ; giving an
account of some experiments
on their strl'cture and func-
tions, which lead to a new
arrangement of the system.
By Charles Bell, Esq., commu-
nicated by Sir Humphrev Daw,
Bart., P. R. S. Read, July 12,
1821. Philosophical Transac-
tions, London, 1821, Part L, p.
398, et seq.

Original

Of THE TRIGEMINUS, OR FIFTH

PAIR. In all animals that have
a stomach, with palpi or tentac-
ula to embrace their food, the
rudiments of this nerve may be
perceived ; and always in the
vermes, that part of their nerv-
ous system is most easily dis-
cerned which surrounds the
•oesophagus near the mouth. If
a feeler of any kind project
from the head of an animal,
whether the antenna of a lob-
ster or the trunk of an elephant,
it is a branch of this nerve
■which supplies sensibility to the
member and animates its mus-
cles. But this is only if it be
a simple or^an of feeling, and
is not in its office connected with
respiration.

On THE nerves; giving a

VIEW OF THEIR STRUCTURE AND
ARRANGEMENT, WITH AN AC-
COUNT OF SOME EXPERIMENTS
ILLUSTRATIVE OF THEIR FUNC-
TIONS. From the Philosophical
Transactions, 1821, with some
additional explanations. — The
nervous system of the human
body, as explained in a series of
papers read before the Royal
Society of London. By Sir
Charles Bell, K. G. H., etc., etc.
Third edition, London, 1844, p.
33, et seq.

Reprint

Of THE TRIGEMINUS, OR FIFTH

PAIR, the nerve of sensation and
mastication. In all animals that
have a stomach, with palpi or
tentacula to embrace their food,
the rudiments of this nerve may
be perceived ; and always in the
vermes, that part of their nerv-
ous system is most easily dis-
cerned which surrounds the
oesophagus near the mouth. If
a feeler of any kind project
from the head of an animal,
whether the antenna of a lob-
ster or the trunk of an elephant,
it is by a branch of this nerve
that it is supplied with sensibil-
ity. But if it be not merely a
simple organ of feeling, but in
its office connected with respira-
tion, another nerve is added.
The trunk of the elephant is not
a simple feeler; it is a tube
through zvhich it respires, and
therefore it has a different
nerz'e superadded, to move it as
a hand, and to expand it in the
act of inspiration.

* The passages that have been altered are printed in italics.
4

5°

ROOTS OF THE SPINAL NERVES

From the nerve which comes
off from the anterior ganglion
of the leech, and which supplies
its mouth, we may trace up
through the gradations of ani-
mals a nerve of taste and man-
ducation, until we arrive at the
complete distribution of the
fifth, or trigeminus, in man.
Here in the highest link, as in
the lowest, the nerve is subser-
vient to the same functions. It
is the nerve of taste and of the
salivary glands; of the muscles
of the face and jaws, and of
co)nnion sensibility. It comes
off from the base of the brain in
so peculiar a situation, that it
alone, of all the nerves of the
head, receives roots both from
the medullary process of the
cerebrum and the cerebellum.
A ganglion is formed upon it
near its origin, though some of
its filaments pass on without en-
tering into the ganglion. Be-
fore passing out of the skull, the
nerve splits into three great
divisions, which are sent to the
face, jaws, and tongue. Its
branches go minutely into the
skin, and enter into all the mus-
cles, and they are especially
profuse to the muscles which
move the lips upon the teeth
— (pp. 409, 410).

From the nerve which comes
off from the anterior ganglion
of the leech, and which supplies
its mouth, we may trace up
through the gradations of ani-
mals a nerve of taste and man-
ducation, until we arrive at the
complete distribution of the
fifth, or trigeminus, in man.
Here in the highest link, as in
the lowest, the nerve is subser-
vient to the same functions. It
is the nerve of the muscles of
the jaws, and of common sensi-
bility, of taste, and of the sali-
vary glands. It comes off from
the base of the brain in so pecid-
iar a situation, that it alone, of
all the nerves of the head, re-
ceives roots both from the col-
umn of sensibility and that of
motion. A ganglion is found
upon it near its origin, though
some of its filaments pass on
without entering into the gan-
glion. Before passing out of
the skull, the nerve splits into
three great divisions, which are
sent to the face, jaws, and
tongue. Its branches go mi-
nutely into the skin, and enter
into all the muscles, and they
are especially profuse to the
lips— (pp. 47, 48).

Of the respiratory nerve
of the face, being that
which is called the portio
dura of the seventh.

Of THE PORTIO DURA OF THE

SEVENTH NERVE THE MOTOR

AND RESPIRATORY NERVE OF
THE FACE.

In this extensive distribution,
the nerve penetrates to all the
muscles of the face ; muscles
supplied also zvith the branches
of the fifth pair. Its branches
penetrate to the skin accom-
panying the minute vessels of
the cheek — (p. 411).

In this extensive distribution,
the nerve penetrates to all the
muscles of the face ; muscles
supplied also with the sensitive
branches of the fifth pair —
(P- 50).

ROOTS OF THE SPINAL NERVES

51

Experiments on the nerves
OF THE face.

An ass being thrown, and its
nostrils confined for a few sec-
onds, so as to make it pant and
forcibly dilate the nostrils at
each inspiration, the portio dura
was divided on one side of the
, head; the motion of the nostril
of the same side instantly ceased,
while the other nostril contin-
ued to expand and contract in
unison with the motions of the
chest.

On division of this nerve, the
animal will give no sign of
pain ; or in no degree equal to
what results from dividing the
fifth nerve.

An ass being tied and thrown,
and the superior maxillary
branch of the fifth nerve ex-
posed, touching this nerve gave
acute pain. It zvas divided, but
no change took place in the mo-
tion of the nostril ; the cartil-
ages continued to expand regu-
larly in time with the other
parts, which combine in the act
of respiration. If the same
branch of the fifth be divided
on the opposite side, and the
animal let loose, he will not pick
up his corn ; the power of ele-
vating and projecting the lip, as
in gathering food, was lost.
He will press the mouth against
the ground, and at length will
lick the oats from the ground
with his tongue. In my first
experiment, the loss of motion
of the lips Tvas so obvious, that
it was thought a useless cruelty
to cut the other branches of the
fifth— (pp. 412, 413).

Experiments on the nerves
OF the f ace, zvith avicwto ascer-
tain the uses of the portio dura.

If an ass be thrown, and the
portio dura be cut across where
it emerges upon the face, before
the ear, all the muscles of the
face, except those of the jaws,
zcill be paralysed. If its nos-
trils be confined for a fezv sec-
onds, so as to make it pant and
forcibly dilate the nostrils at
each inspiration, and if the por-
tio dura be nozu divided on one
side of the head, the motion of
the nostril of the same side will
instantly cease, zuhile the other
nostril zvill continue to expand
and contract in unison zvith the
motions of the chest.

On division of this nerve, the
animal will give no sign of
pain ; or in no degree equal to
what results from dividing the
fifth nerve.

If an ass be tied and thrown,
and the superior maxillary
branch of the fifth nerve ex-
posed, touching this nerve gives
acute pain. When it is divided,
no change takes place in the
motion of the nostril ; the car-
tilages continue to expand reg-
ularly in time with the other
parts which combine in the act
of respiration; but the sensibil-
ity is entirely lost. If the same
branch of the fifth be divided
on the opposite side, and the
animal let loose, the parts will
be deprived of sensibility, and
he will not pick up his corn : the
power of elevating and project-
ing the lip, as in gathering food,
zvill appear to be lost. He will
press the mouth against the
ground, and at length lick the
oats from the ground with his
tongue. In my first experi-
ments the loss of sensibility of
the lips zuas so obvious, that it

52

ROOTS OF THE SPINAL NERVES

From these facts we are en-
titled to conclude, that the por-
tio dura of the seventh is the
respiratory nerve of the face ;
that the motions of the lips, the
nostrils, and the velum palati,
are governed by its influence,
when the muscles of these parts
are in associated action with the
other organs of respiration —
(p. 414).

Of the functions of the
trigeminus, or fifth nerve,
as illustrated by these ex-
periments.

was thought a useless cruelty to
cut the other branches of the
fifth — (p. 52).

From these facts we are en-
titled to conclude, that the por-
tio dura of the seventh is the
nerve of motion to the muscles
of the forehead, eyebrow, eye-
lids, nostril, lips, and ear; that
is, to all the muscles of the face
except those of mastication —
that it is the respiratory nerve
of the face ; that the motions of
the lips, the nostrils, and the
velum palati, are governed by
its influence, when the muscles
of these parts are in associated
action with the other organs of
respiration — (p. 54).

Of the FUNCTIONS OF THE
TRIGEMINUS, OR FIFTH NERVE.

Independently of the differ-
ence of sensibility in these
nerves, there was exhibited, in
all these experiments, a wide
distinction in their powers of
exciting the muscles. The
slightest touch of the portio
dura, or respiratory nerve, con-
vulsed the muscles of the face,
whilst the animal gave no sign
of pain. By means of the
branches of the fifth nerve, it
was more difficult to produce
any degree of action in the
muscles, although, as I have
said, touching the nerve gave
great pain — (p. 58).

Independently of the differ-
ence of sensibility in these
nerves, there was exhibited, in
all these experiments, a wide
distinction in their powers of
exciting the muscles. The
slightest touch of the portio
dura, or respiratory nerve, con-
vulsed the muscles of the face,
whilst the animal gave no sign
of pain. By means of the
branches of the fifth nerve, it
zvas not possible to excite the
muscles, if the trunk of the
nerve were divided behind the
part bruised; that is to say, if
the communication with the
sensorium zvere cut off — (p. 58).

The paper from- which the above extracts are made does
not treat directly of the spinal nen'es, but many passages
are so worded in the reprint as to make it appear that its
author recognized fully the distinction between the motor

ROOTS OF THE SPINAL NERVES 53

and the sensory nerves throughout the system; and, as be-
fore remarked, it has been referred to by Shaw and others
as evidence that these facts were well known before the
publication of Magendie's experiments. In republishing
a paper of this kind, the author undoubtedly had a right
to make such additional explanations and such corrections
as might be demanded by the advanced state of knowledge
on the subject; but such alterations should have been so
introduced as to be distinguishable from the original mat-
ter. Many additions, not bearing on the subject under con-
sideration, have not been quoted; * and I have noted some
unimportant alterations so as not to destroy the sense of
the extracts; but a careful comparison of some of the pas-
sages which have been put side by side will make it evident
that most of Sir Charles Bell's definite knowledge regard-
ing the seat of motion and sensation in the nervous system
was acquired after the first publication in the " Philosoph-
ical Transactions."

In the first extract, in speaking of a branch of the fifth,
it will be seen that Bell confounds the two properties of
motion and sensation; but he corrects this error in the
reprint. He again speaks of this nerve as receiving roots
from the medullary process of the cerebrum and the cere-
bellum; wdiich, in the reprint, he calls " the column of sensi-
bility and that of motion." In the first publication he calls
the portio dura simply the '* respiratory nerve of the face; "
and in the reprint he has modified his phraseology, and
speaks of it as the " motor and respiratory nerve of the
face." In another place he details an experiment in which
the superior maxillary branch of the fifth was divided in an
ass; and in the reprint he states that sensibility was entirely
lost, etc., but does not mention this in his original paper.
He also says, in the same connection, that after this opera-
tion '■' the loss of motion of the lips was so obvious," etc.,
and in the reprint he has it that " the loss of sensibility of
the lips was so obvious." A careful study of the first mem-
oir will show that he never made correct applications of
the terms motor and sensory with reference to different

* The alterations from the original publication in the " Philosophical Trans-
actions " are much more extensive in the late editions of the work on the nerves
than in the previous issues. In an edition reprinted in this country (Washing-
ton, 1833) the corrections are much fewer.

54 ROOTS OF THE SPINAL NERVES

portions of the nervous system; and that this memoir of
1 82 1 added nothing, as regards the discovery of the func-
tions of the roots of the nerves, to the paper printed in
1811.*

II

REVIEW OF THE CLAIMS OF MAGENDIE TO THE DISCOVERY
OF THE DISTINCT PROPERTIES OF THE ROOTS OF THE
SPINAL NERVES

The first publications of rvlagendie concerning the anat-
omy and the functions of different portions of the nerv-
ous system appeared in the " Journal de physiologic," in
1821. In the first volume of this journal is a notice of the
researches of Charles Bell on the nerves of the face, with
an account of the observations of Mr. Shaw on the same
subject. f Magendie here states that he repeated the ex-
periments of Bell with MM. Shaw and Dupuy at Alfort.:}:
Magendie had not at that time received the memoir of Bell;
but in a succeeding number of the Journal he gives a full
analysis of it.* In this number, also, he speaks of having
repeated the experiments. In the same Journal follows a
translation of the experiments of Mr. Shaw.|i In none of
these publications is there any allusion to the properties of
the anterior and posterior roots of the spinal nerves, nor
is there any evidence that either Bell, Shaw or Magendie
knew anything about the distinct seat of motion and sensa-
tion in the spinal cord and the spinal nerves.'^

* A paper by Mr. John Shaw, in the " Medico-Chirurgical Transactions,"
in June, 1822, some months before Magendie's experiments were published, is
said to contain an account of Bell's views of the nerves. The statements here,
however, are no more definite than the quotations which I have made from
Bell's original writings.

f " Recherches anatomiques et physiologiques sur le systeme nerveux ; "
par M. Charles Bell. — "Journal de physiologie," Paris, 1821, tome i., p. 384,
et seq.

X Loc. cit., p. 387.

* " Suite des recherches anatomiques et physiologiques sur le systeme ner-
veux," par M. Bell. — "Journal de physiologie," Paris, 1S22, tome ii., p. 66,
et seq.

II " Experiences sur le systeme nerveux ; " par M. Shaw. Extrait et tra-
duit de I'Anglais par M. Cairns. — "Journal de physiologie," Paris, 1822, tome
ii., p. 77, et seq.

^ In the same volume of the Journal (p. 363), Magendie gives an account of
Bell's observations on the respiratory nerves of the chest, which were presented
to the " Royal Society," May 2, 1822.

ROOTS OF THE SPINAL NERVES 55

In August, 1822 Magendie published his first experi-
ments on the functions of the roots of the spinal nerves."^
Unlike any of the experiments performed by Bell on
the spinal nerves, these were made upon living animals.
The spinal canal was opened, and the cord, with the roots
of the nerves, exposed. The posterior roots of the lumbar
and sacral nerves were then divided upon one side and the
wound united with sutures. The result of this ol^servation
was as follows: f

" I thought at first that the limb corresponding to the divided
nerves was entirely paralyzed; it was insensible to pricking and
to the most severe pinching, it also appeared to me to be motionless ;
but soon, to my great surprise, I saw it move in a very marked man-
ner, although the sensibility was still entirely extinct. A second,
a third experiment, gave me exactly the same result; I commenced
to regard it as probable that the posterior roots of the spinal nerves
might have functions different from the anterior roots, and that
they were more particularly devoted to sensibility." ^

The experiments in which the anterior roots were di-
vided were no less striking:

" As in the preceding experiments, I only made the division
upon one side, in order to have a term of comparison. One can
conceive with what curiosity I followed the effects of this division ;
they were not at all doubtful, the limb was completely motionless
and flaccid, while it preserved a marked sensibility. Finally, that
nothing should be neglected, I divided at the same time the anterior
and the posterior roots ; then followed absolute loss of sensation and
of motion." *

* " Experiences sur las fonctions des racines des nerfs rachidiens ; " par
F. Magendie. — " Journal de physiologie," Paris, 1822, tome ii., p. 276, et seq.

f The original of the important passages quoted from Magendie is given in
foot-notes, and the translation into English is as nearly literal as possible.

J " Je crus d'abord le membre correspondant aux nerfs coupes, enti^rement
paralyse ; il etait insensible aux piqures et aux pression les plus fortes, il me
paraissait aussi immobile ; mais bientot, a ma grande surprise, je le vis se mou-
voir d'une mani^re tres apparente, bien que la sensibilite y fut toujours tout-a-
fait eteinte. Une seconde, un troisi^me experience, me donnerent exactement
le meme resultat ; je commenfais a regarder comme probable que les racines
posterieures des nerfs rachidiens pourraient bien avoir des fonctions dififerentes
des racines anterieures, et qu'elles etaient plus particuli^rement destinees a la
sensibilite." — (" Journal de physiologie," Paris, 1822, p. 277.)

* " Comme dans les experiences precedentes, je ne fis la section que d'un
seul cote d'avoir un terme de comparaison. On conceit avec quelle curiosite je
suivis les effets de cette section ; ils ne furent point douteux, le membre etait
completement immobile et flasque, tandis qu'il conservait une sensibilite non
equivoque. Enfin, pour ne rien negliger, j'ai coupe a la fois les racines ante-
rieures et les post^rieures ; il y a eu perte absolue de sentiment et de mouve-
ment." — {Ibid., p. 278.)

56 ROOTS OF THE SPINAL NERVES

From these experiments IMagendie drew the following"
conclusions:

" I am following out my researches, and shall give a more de-
tailed account of them in the following number ; it is sufficient for
me to be able to announce at present as positive, that the anterior
and the posterior roots of the nerves which arise from the spinal
cord have different functions, that the posterior seem more par-
ticularly devoted to sensibility, while the anterior seem more espe-
cially connected with motion." *

In the second note, published in the same volume of the
" Journal de physiologic," Alagendie exposed and irritated
the two roots of the nerves, with the following results:

" I commenced by examining in this regard the posterior roots,,
or the nerves of sensibility. The following is the result which I
observed: on pinching, pulling, or pricking these roots, the animal
manifested pain ; but this was not to be compared as regards inten-
sity with that which was developed if the spinal cord was touched,,
even lightly, at the point of origin of the roots. Nearly every
time that the posterior roots were thus stimulated, contractions
were produced in the muscles to which the nerves were distributed;
these contractions, however, are not well marked, and are infinitely
more feeble than when the cord itself is touched. When, at the
same time, a bundle of the posterior root is cut, there is produced
a movement in totality in the limb to which the bundle is distributed.

" I repeated the same experiments on the anterior roots, and I
obtained analogous results, but in an opposite sense ; for the con-
tractions excited by the contusion, the pricking, etc., are very forci-
ble, and even convulsive, while the signs of sensibility are hardly
visible. These facts are, then, confirmatory of those which I have
announced; only they seem to establish that sensation is not exclu-
sively in the posterior roots, any more than motion in the anterior
roots. Nevertheless, a difficulty may arise. When, in the preceding"
experiments, the roots had been cut, they were attached to the spinal
cord. Might not the disturbance communicated to the cord be the
real cause either of the contractions or of the pain which the ani-
mals experienced ? To remove this doubt, I repeated the experi-
ments after having separated the roots from the cord ; and I must
say that, except in two animals, in which I saw contractions when
I pinched or pulled the anterior and posterior roots, in all the other
instances I did not observe any sensible effect of irritation of the
anterior or posterior roots thus separated from the cord." f

* " Je poursuis ces recherches et j'en donnerai un recit plus detaille dans le
prochain numero ; il me suffit de pouvoir avancer aujourd'hui comme positif,
que les racines anterieures et les posterieures des nerfs qui naissent a la moelle
epin^re, ont des fonctions dififerentes, que les posterieures paraissent plus par-
ticulierement destinees a la sensibilite, tandis que les anterieures semblent plus
specialement liees avec la mouvement." — [Ibid., p. 279.)

f " J'ai commence par examiner sous ce rapport les racines posterieures, ou
les nerfs du sentiment. Voici ce que j'ai observe : en pinjant, tiraillant»

ROOTS OF THE SPINAL NERVES 57

Magendie then goes on to say that when he pubHshed
the note in the preceding number of the Journal he sup-
posed that he was the first who had thought of cutting the
roots of the spinal nerves; but he was soon undeceived by
a letter from Mr. Shaw, who stated that Bell had divided
the roots thirteen years before. Magendie afterward re-
ceived from Mr. Shaw a copy of Bell's essay (" Idea of a
New Anatomy of the Brain"), and, as will be seen by the fol-
lowing extract, gave Bell full credit for all his observations.

" It is seen by this quotation from a work which I could not be
acquainted with, inasmuch as it had not been published, that Mr.
Bell, led by his ingenious ideas concerning the nervous system, was
very near discovering the functions of the spinal roots ; still the
fact that the anterior are devoted to movement, while the posterior
belong more particularly to sensation, seems to have escaped him;
it is, then, to having established this fact in a positive manner that
I must limit my pretensions." *

Such are the experiments by w-hich the properties of the
roots of the spinal nerves were discovered. From that time
the fact took its place in science that the posterior roots

piquant ces racines, Tanimal temoigne de la douleur ; mais elle n'est point k
comparer pour I'intensite avec celle que se developpe si Ton louche, meme
legerement, la moelle epinere a Tendroit ou naissent ces racines. Presque
toutes les fois que Ton excite ainsi les racines posterieures il se produit des con-
tractions dans les muscles ovi les nerfs se distribuent ; ces contractions sont
cependant peu marquees, et infiniment plus faibles que si on touche la moelle
elle-meme. Quand on coupe a las fois un faisceau de racine posterieure, il se
produit un mouvement de totalitc dans le membre ou le faisceau va se rendre.

" J'ai repete les memes tentatives sur les faisceaux anterieurs, et j'ai obtenu
de resultats analogues, mais en sens inverse ; car les contractions excitees par
le pincement, la piqure, etc., sont tres-fortes et meme convulsives, tandis que
les signes de sensibilite sont a peine visibles. Ces faits sont done confirmatifs
de ceux que j'ai annonces ; seulement ils semblent etablir que le sentiment
n'est pas exclusivement dans les racines posterieures, non plus que le mouve-
ment dans les anterieurs. Cependant une difficulte pouvoit s'elever. Quand,
dans les experiences 'que precedent, les racines ont ete coupees, elles etaient
continues avec la moelle epinere : I'ebranlement communique k celle-ci ne
serait-il pas la veritable origine soit des contractions, soit de la douleur qu'ont
epreuves les animaux ? Pour lever ce doute, j'ai refait les experiences apres
avoir separe les racines de la moelle ; et je dois dire qu'excepte sur deux ani-
maux, ou j'ai vu des contractions quand je pin9ais ou tiraillais les faisceaux
anterieurs et posterieurs, dans tous les autres cas je n'ai obsei-ve aucun effet
sensible de I'irritation des racines anterieures ou posterieures ainsi separees de
la moelle." — {Ibid., p. 368.)

* "On voit par cette citation d'un ouvrage que je ne pouvois connaitre,
puisqu'il n'a point ete publie, que M. Bell, conduit par ces ingenieuses idees
sur la systeme nerveux, a ete bien pres de decouvrir les fonctions des racines
spinales ; toutefois le fait que les anterieures sont destinees au mouvement,
tandis que les posterieures appartiennent plus particulierement au sentiment,
parait lui avoir echappe : c'est done a avoir etabli ce fait d'une maniere positive
que je dois borner mes pretentions." — {Ibid., p. 371.)

58 ROOTS OF THE SPINAL NERVES

are for sensation and the anterior for motion. Some dis-
cussion has arisen as to whether the anterior roots do not
possess a certain degree of sensibihty, called recurrent sen-
sibility, and this question has engaged the attention of phys-
iologists with a few years; * but the distinct functions of
the two roots have never been doubted. It has already been
seen what use Bell made of these facts in late editions
of his work on the nervous system. Before the days of
anesthetics, exposing the roots of the nerves in the dog
was very laborious, and painful to the animal, and the dis-
turbances produced by so serious an operation interfered
somewhat with the effects of irritation of the different roots.
But now that the canal may be opened without pain to the
animal, the experiments are much more satisfactory and
have often been repeated by physiologists. I have fre-
quently, indeed, demonstrated the properties of the roots
of the nerves in public teaching.f

Although, as has been seen, almost all physiological
writers, even in France, regarded Bell as the real discov-
erer, Magendie continued to claim that he first positively
ascertained the seat of motion and sensation in the spinal
nerves. In 1823, after reiterating his statements in regard
to the nerves, he extended his researches to the cord itself,
and demonstrated that the anterior columns are motor and
the posterior columns sensory. :{: In all his subsequent
publications the same statements are made.*

* Bernard, " Le9ons sur la physiologic et la pathologie du systeme ner-
veux." Paris, 1858, tome i., p. 20, et seq. Even Bernard, a pupil, and for a
long time the " preparateur " for Magendie, at one time seemed to regard Sir
Charles Bell as the discoverer of the functions of the roots of the spinal nerves
(ibid., p 25, and " Lecons sur les effets des substances toxiques et medica-
menteuses." Paris, 1857, p. 20) ; in a late worlc, however, in which this whole
subject is reviewed, the claims of Magendie to the discovery are fully recog-
nized (Bernard, " Rapport sur les progres et la marche de la physiologic gene-
rale en France." Paris, 1867, pp. 12 and 154). Bernard states that he was
unable to obtain the original memoir of Bell, printed in l8ri, but finally pro-
cured an exact copy, which is probably the reprint of 1839. {IHd., p. 155.)

f Flint, " Experiments on the Recurrent Sensibility of the Anterior Roots
of the Spinal Nerves." — " New Orleans Medical Times," 1861, p. 21, et seq.

At the time that this paper was written, I had not had an opportunity of
consulting the original memoir of Sir Charles Bell, and, with others, I regarded
him as the discoverer of the functions of the roots of the nerves. I have also
had occasion to modify the views therein expressed concerning the recurrent
sensibility of the anterior roots.

\ Magendie, " Note sur le siege du mouvement et du sentiment dans le moel-
le epinere." — " Journal de physiologic," Paris, 1823, tome iii., p. 153, et seq.

* Desmoulins et Magendie, "Anatomic des systemes nerveux des animaux

ROOTS OF THE SPINAL NERVES 59

Shaw, in his " Narrative," states that in 1822 Magen-
die " admitted that the experiments on the roots of the
spinal nerves, which he had claimed as original, had been
performed many years before by Sir Charles Bell." * This
is not correct; and I have already quoted in full the passage
in which Magendie gives Bell full credit for what he had
done, but expressly states that the fact that the anterior
roots preside over movements and the posterior over sensa-
tion seems to have escaped him. Shaw also quotes Des-
moulins and Magendie as admitting '* that there is no ab-
solute distinction between the functions possessed by the
two roots; " f but in doing this he translates the expres-
sion into English incorrectly. In the passage referred to,
it is stated that " L'isolement des deux proprietes dans
chacun des deux ordres de racines, n'est done pas absolu,"
which simply means that the motor roots are not absolute-
ly without sensibility and the sensory roots are not abso-
lutely devoid of motor properties.

The experiments of Magendie made in 1822 must stand
without further question as the first to demonstrate the true
properties of the two roots of the spinal nerves; and be-
fore the publication of these experiments no physiologist
had a correct idea, theoretical or experimental, of the seat
of motion and sensation in these nerves. There can be no
doubt that the honor of this discovery belongs exclusively
to Magendie.

CONCLUSION

In its bearing on future knowledge in physiology, no
discovery can be regarded as equal to that of the circula-
tion of the blood, by Harvey. But since this, which marks
a great epoch in science, there has been nothing so impor-
tant as the location of the properties of motion and sensa-
tion in different portions of the cerebro-spinal nervous sys-
tem. From this dates nearly all positive knowledge
concerning the functions of this system. For many years
the credit of this great discovery has been either indefinitely
or incorrectly assigned by the great majority of physio-
logical writers, simply because few had an opportunity of
consulting for themselves the original pamphlet in which

k vertebres." Paris, 1825, tome ii., p. 777. Magendie, " Pre'cis elementaire de
physiologic," deuxieme edition. Paris, 1825, tome i., pp. 167, 216, et quatrieme
edition, 1836, tome i., pp. 200, 266. * 0/>. cit., p. 156. f Op. cit., p. 168.

6o ROOTS OF THE SPINAL NERVES

the first observations of Charles Bell, the reputed discover-
er, are contained. If Bell or his defenders had published
this memoir, which is only twenty pages in length, entire,
he would undoubtedly have received full credit for all the
advances which he really made in the physiology of the
nervous system, and no injustice would have been done to
others. Having obtained a complete and authentic reprint
of the original memoir, I have endeavored to review it care-
fully and dispassionately, quoting all the passages which
bear upon the functions of the nerves, in the hope of being
able to settle forever the respective claims of Sir Charles
Bell and Magendie to this discovery. From a review of
this and other papers l)y Walker, Bell, Shaw and Magendie,.
the following conclusions are inevitable:

Like many great discoveries, the idea, and the experi-
ments by which it was carried out and elaborated, did not
emanate from a single mind.

In 1809, Alexander Walker proposed for the first time
the theory that the properties of motion and sensation in
the mixed nerves were derived from the two roots by which
they take their origin from the spinal cord. This idea w^as
entirely theoretical; and sensation was assigned to the an-
terior root and motion to the posterior root.

In 181 1, Charles Bell, who was the first to experiment
on the spinal nerves in animals recently killed, ascertained
by experiment that the posterior roots of the spinal nerves
had hardly any motor properties. He ascribed both mo-
tion and sensation to the anterior roots and supposed that
the posterior roots presided over w-hat are now known as
the vegetative, or organic functions. He knew nothing
about the sensibility of the posterior roots.

In 1822, F. Magendie, who was the first to experiment
on the spinal nerves in living animals, ascertained by ex-
periment that the anterior roots of the spinal nerves pre-
sided over movement and the posterior roots over sensa-
tion. He believed these to be distinct functions of these
roots, but he thought at that time that the anterior roots
might be slightly sensitive and the posterior roots might
possess some motor properties.

From the experiments of Magendie dates all positive
knowledge of the physiological properties of the two roots
of the spinal ner\^es.

V

EXPERIMENTAL RESEARCHES ON POINTS
CONNECTED WITH THE ACTION OF THE
HEART AND WITH RESPIRATION

Published in the " American Journal of the Medical Sciences " for October,

1 86 1.

It is not intended in this paper to take up all points
•connected with either of the functions which will come un-
■der consideration. This of course would be inconsistent
wdth its scope; for many are so demonstrable and now so
well established that their consideration here would be a
mere recapitulation of facts well known and universally
admitted. It is rather my object to present some original
•experiments by which I hope to elucidate points which are
yet subjects of dispute among physiologists and which,
in my opinion, cannot be settled by argument alone, but
are capable of being brought under direct obsen^ation
and if established can be made subjects of actual demon-
stration. Some functions can not as yet be disclosed to
the senses in their natural operation; but others, which
are connected with questions here to be considered, re-
quire only correct description to serve as facts from
which each inquirer may make his own deductions. For
the understanding of those processes which can easily be
described and about which there can be no mistake, noth-
ing usually is necessary but simple observation; but there
are others, more delicate and obscure, which different ex-
perimenters see in different ways. In the investigations
into their phenomena one should strive to perfect methods
of observation, to devise means by which all confusing
circumstances may be removed, to invent instruments
which will make them more prominent, so that any ob-
server, willing to take the trouble to look for himself, can
see and interpret them in but one way. This is no less a

6i

62 ACTION OF THE HEART AND RESPIRATION

desideratum in physiological than in pathological investi-
gations; and means of physical exploration should be
sought which will be to the physiologist what the stetho-
scope, the speculum, the ophthalmoscope and our many
modern exploring instruments are to the pathologist. Ob-
stetricians might differ in regard to conditions of the os
uteri, exploring only by the touch, when the speculum, ex-
posing the parts to the eye, would leave no room for dis-
cussion; auscultators, listening with the naked ear through
the clothing of a patient, might dispute about sounds heard
within the thorax, when they would agree if a stethoscope
were applied to the naked chest. I'hus, perfected appa-
ratus enables the chemist and physiologist to demonstrate
facts that would be obscure with less certain means of in-
vestigation. Many points in the physiology of the heart
and of respiration are yet undecided; and it is by removing
some sources of self-deception in the simple observation
of phenomena and by multiplying demonstrable facts, the
only true basis of general deductions, that I have endeav-
oured to go a step beyond what is already known and es-
tablished.

The questions which I shall take up in this essay are,
with reference to the heart:

First: Does the organ shorten or elongate during its
ventricular systole, or contraction?

Second: How far is it possible to determine the cause
of its regular and periodic action?

Third: What are some of the causes of arrest of the
action of the heart?

Fourth: What is the mechanism of some of the nervous
influences over the action of the heart?

Fifth: What is the mechanism of the action of the
valves which guard the orifices of the heart?

And, in regard to respiration: What is the cause, and
w^here is the seat of the impression, or " besoin de respirer,"
which is conveyed to the respiratory centre and which ex-
cites the action of the muscles of inspiration?

These questions have either never been fully under-
stood by physiologists or are now explained in a contra-
dictory manner in the various systematic physiological
treatises.

ACTION OF THE HEART AND RESPIRATION 6^

It was with the hope of contributing something to the
further ehicidation of these obscure and disputed points
that the experiments which form the basis of this paper
have been undertaken.

Changes in Consistence, Position and Form of
THE Heart during its Action. — In regard to the move-
ments and action of the heart, there is manifestly but one
correct mode of study, and that is the one which led Har-
vey to make the discovery of the circulation of the blood.
This method is to expose the heart in living animals during
its action and observe its movements. This may be done
in various animals and in different ways. It is easy to ob-
serve the heart in action in the cold-blooded animals, by
simply removing the anterior walls of the thorax; and its
contractions will continue for a long time after such an
operation and even after the organ has been entirely sepa-
rated from the body. Such observations give a great deal
of information but are made more valuable when compared
with phenomena observed in warm-blooded animals, in
which the heart resembles the corresponding organ in
man. In operating upon the heart of these animals, such
as dogs, cats, sheep or horses, it is necessary to keep up
artificial respiration, as this function can not, of course, be
performed by the animal after the thorax has been opened.
Here it is convenient as well as humane to abolish sensi-
bility by some means which will not interfere with the
heart's action. This may be done by crushing the medulla
oblongata in such a way as to avoid hemorrhage, as done
by Erichsen and Pavy, of London; by stunning the ani-
mal with a blow upon the head, as done by Drs. Pennock
and Moore; by decapitation and ligature of the vessels of
the neck, as done by Legallois; by inoculation with curara
or by the administration of ether or chloroform, which are
the most convenient methods and those now most com-
monly employed by physiologists. The experiments which
I have made have been performed upon animals rendered
insensible by curara or ether; and I have been accustomed
to operate in the following way:

The animal, preferably a good-sized dog, is first poi-
soned with curara by injecting about a grain of this sub-
stance into the subcutaneous areolar tissue or is completely

64 ACTION OF THE HEART AND RESPIRATION

etherized. If poisoned with curara, its cllects are watched,
and in ten to thirty minutes the dog comes under its in-
lluence; more readily, if he is made to move about. If
ether is used, he is rendered insensible in the ordinary way.
The trachea is then opened and the nozzle of a bellows is
introduced for the purpose of keeping- up artificial respi-
ration. An incision is then made in the median line from
the top of the sternum to a point a little below the ensi-
form cartilage, through the skin, fascia and fat. The next
step is to cut through the superficial muscles the whole
length of the sternum on each side, about an inch from
the median line, down to the costal cartilages, and then to
tear away the muscles from the chest, exposing the ribs.
The next step, after having exposed the chest in this man-
ner, is to saw through the sternum in the median line, open-
ing into the thoracic cavity; then to hold open the chest
by sticks, or what is more convenient, to cut across the
ribs on each side with a pair of strong cutting pliers, turn
back the anterior walls of the thorax and retain them in
that position by a strong ligature passed under the back of
the animal and firmly tied. In this way, the lungs, which
are regularly inflated with the bellows, are exposed and be-
tw'een them is seen the heart enclosed in its pericardium.
The pericardium may then be removed by slitting it up and
cutting it away from its attachments at the base of the
heart, w^hich may then be observed in the natural perform-
ance of its functions.

When the heart of a dog is exposed in this way, one of
the most constant effects is an increase in the rapidity of its
contractions. The pulse of a dog is always irregular in a
state of health, varying between lOO and 120 beats in the
minute. When the heart is exposed its pulsations become
more frequent, sometimes numbering 200 to 250.

The phenomena which are observed in connection with
the contraction of the ventricles are:

I. Hardening. — This is a phenomenon constantly at-
tending muscular contraction. It was described by Har-
vey, who proved that it took place during contraction of
the ventricles, by introducing a small canula through the
walls of the left ventricle, applying the hand to the heart
and noticing that the hardening took place when a jet of
blood was forced through the canula. Nearly all physio-

ACTION OF THE HEART AND RESPIRATION 65

logical authors are agreed on this point, although Dr.
Wood, late of the University of Pennsylvania, was of the
opinion that the heart hardens during the diastole. I have
repeatedly verified the fact that the heart hardens during
the systole by repeating the experiment of Harvey. One
who examines the heart in action can hardly be mistaken
in regard to this point.

II. Tilting Upwards of the Point of the Heart
AND Locomotion of the Apex from Left to Right. —
About this phenomenon there is no difference of opinion.
It can easily be observed in vivisections, and this movement
would be expected from the spiral and oblique course of
the superficial fibres of the heart from right to left, arising
at the base and inserted, as it were, into the apex, which
is free.

III. Twisting from Left to Right. — This can be ob-
served by examining the apex of the heart. It is univer-
sally admitted by physiologists and is explained by the
spiral course of the fibres from right to left. This phe-
nomenon, like the preceding, I have repeatedly ob-
served.

IV. Elongation of the Ventricles. — This change
in the length of the ventricles is denied by modern French,
English and German physiologists, who seem all to agree
that Harvey was wrong in this part of his description of
the action of the heart. Harvey, Vesalius, Riolan, Fon-
tana, Borelli. Winslow and Oueye contended for the elon-
gation of the organ during its systole; but this view was
•combated by Steno, Lancisi, Bassuel and Haller. It seems
to me that the prevalence of the opinion, at the present
■day, that the heart shortens during systole can be attributed
in great measure to the weight of the opinion of Haller.
I am fortunate in having an opportunity of referring to an
edition of his original works, published in 1757, and could
not but be struck with its similarity in views, in arguments,
and sometimes even in actual mode of expression, when
treating of the change in the length of the heart during the
systole, with the works on physiology which are now used
as text-books, especially those by French authors.

Haller bases his views on his own experiments upon
a case of ectropy of the heart (" Denique in puero, cui cor
•extra pectus propendebat, cor in diastole longius, et in sys-

5

66 ACTION OF THE HEART AND RESPIRATION

tole brevius factum est, perinde ut in l)estiis videnuis " *)
and on an argument of Bassuel. This last argument against
the elongation of the heart is employed by many physiolo-
gists of the present day. Haller, after stating the views and
arguments of Vesalius, Riolan and others, says:

" Varia nupcrrimi scriptores reposuerunt. Et quidem CI. Bas-
suel ad argumentum a valvulis venosis repetitum rcspondit, earum
fabricam contra adversaries facere. Si enim in systole cordis mu-
cro a basi recideret, tunc certe sequeretur, ut adtractis ad apicem
funiculis, valvulse in cordis caveam deductae ostium aperirent, san-
guinique venoso earn viam referarent, quam utique clausam esse
oportet, dum cor contrahitur Mihi vero videtur, valvulas quidem
venosas eo tempore a sanguine versus aures repulso extrorsum,
inque aurium cavitates cessuras, nisi a musculis suis papillaribus,
eo ipso tempore se decurtantibus, retinerentur, inque ventriculum
reducerentur.

" Aliud experimentum addidit CI. Bassuel ; cor nempe aqua re-
plevit, viditque, dum brevius fiebat, aquam expelli." f

I have exposed thus fully the views of Haller on this
subject, because of the commanding influence he so long
exercised in the physiological world, and especially be-
cause, on this point, late authors seem to have followed
him so closely. In addition it may not be uninteresting
to cite a few of the authorities who favor the shortening of
the heart during its systole.

Todd, in the article on the heart in the " Cyclopedia of
Anatomy and Physiology," speaking of the organ during
its systole, says: " In all warm-blooded animals, at least,
it becomes shortened."

Carpenter, in the '' Principles of Human Physiology,"'
London, 1855, page 226, says:

" During their contraction, the form of the ventricles undergoes
a very marked change, the apex of the heart being drawn up
towards its base, and its whole shape becoming much more glob-
ular."

Kirkes, " Handbook of Physiology," in speaking of the
action of the ventricles, says:

" They contract much more slowly than the auricles, and simul-
taneously in every part, the whole wall of each ventricle being
drawn up uniformly towards the origin of the artery at its base,
diminishing the cavity in every diameter, but especially in length,
so that the heart assumes a shorter and more globular form than it
had in the relaxed and distended state of the ventricles."

* " Elementa Physiologiae," tome i., p. 392. + Ibid., tome i., p. 391.

ACTION OF THE HEART AND RESPIRATION 67

Among the French authors is Beclard, " Traite de phys-
iologie," Paris, 1856:

" Le Raccourissement general de I'organe, au moment de la
contraction des oreillettes, est assez limite. Son plus grand rac-
courssement coincide avec la contraction des ventricles, qui I'em-
porte par dimensions les oreillettes "... " chez quelques animaux,
le raccourissement suivant la verticale est moins prononce que le
raccourissement sur I'horizontale, ce qui a fait penser faussement
a quelques observateurs que le cceur s'allonge pendant la systole
ventriculaire."

Richerand, " Elements de physiologie." tome i., p. 478,
says :

" D'apres cela, il est evident que le coeur se raccourcit," meaning
during the systole.

Beraiid, " Elements de physiologie," revus par Ch.
Robin, tome ii., p. zyy, says, speaking of the systole:

" Le sommet des ventricles se rapproche de la base et du som-
met, il suit de la que la coeur se raccourcit."

Magendie, " Precis elementaire de physiologie," tome
ii., p. 395, says:

" Les partisans de I'allongement ne persistent plus ; mais il re-
stait a demontrer comment, les ventricules se raccourissant, le coeur
se porte en avant."

Berard, " Cours de physiologie," Paris, 1851, tome iii.,
p. 603, speaking of the systole, says:

" Le sommet des ventricules se rapproche de la base, et la base
du sommet ; il suit de la que le coeur se raccourcit."

M. H. Milne Edwards, in his " Leqons sur la physiol-
ogie et I'anatomie comparee de I'homme et des animaux,"
tome iv., p. 19, now in course of publication, in speaking
of the systole of the heart, says:

"En effet, il devient presque circulaire a sa base; la portion
voisine de la region ventriculaire se bombe d'une maniere assez
reguliere, et la portion inferieure qui avoisine la pointe retrecit et
se raccourcit."

Finally, in the " Traite de physiologie consideree com-
me science d'observation," par C. F. Burdach, Professor a
rUniversite de Konigsberg, translated into French by Jour-
dan, are to be found the opinions of the German physi-
ologists; for Burdach w'as assisted in the preparation of this

68 ACTION OF THE HEART AND RESPIRATION

work by Baer, Mayen, Meyer, J. Miillcr, Rathke, Valentin,
and Wagner: tome vi., p. 234, he says:

" La contraction, ou systole, s'opere avec la rapidite de I'eclair.
Le coeur se reserre sur lui-meme ; il devicnt plus forme et plus dur ;
il se raccourcit, c'est a-dire que sa base et son sommet se recourbe
un peu."

It is thus seen what a weight of authority there is in
favor of the shortening of the heart during the systole,
all of the English, French and German authors holding
this opinion, and all of them denying the description of
Harvey, who states that the heart elongates during con-
traction; " that it is everywhere contracted, but more espe-
cially towards the sides, so that it looks narrower, relatively
longer, more drawn together." * It is only in this country
that this opinion has been controverted; and though ex-
periments have been made in England, with reference to
this point, f they confirmed the prevalent view, and Amer-
ican experiments thus far have stood alone.

In November, 1839, Drs. Pennock and Moore made a
number of experiments upon the hearts of rams and young
calves, in order to settle disputed points in the change of
the form of the heart during its action, and the mechanism
of the production of the heart sounds. These were pub-
lished in the " Philadelphia Medical Examiner," No. 44,
and also in the American edition of " Hope on the Heart,"
1846. page 59. It is not my object minutely to detail these
experiments; I shall simply state that the animals oper-
ated on were stunned by a blow on the head, a bellows was
introduced into the trachea, by means of which artificial
respiration was kept up, the chest was opened and the
movements of the heart were observed. With reference
to the form and length of the heart during its systole, in all
of these experiments, Drs. Pennock and Moore found that
the heart elongated. Its elongation was measured with
an ordinary shoemaker's rule and found in one experiment
on a ewe one year old, to be one-quarter of an inch.

There are many sources of dif^ficulty in examining a
phenomenon apparently so simple as that of elongation

* Harvey's Works, published by the Sydenham Society, page 21.

f Experiments on the Motions and Sounds of the Heart, by the London
Committee of the British Association for i838-'39 and l839-'40. Experiments
for 1839-40. " Hope on the Heart," Amer. ed., 1846, p. 65.

ACTION OF THE HEART AND RESPIRATION 69

or shortening during the systole of the heart. In the first
place, in the warm-blooded animals, as the dog, the heart's
action is so rapid that it is difficult at first to determine,
even, which is the systole and which is the diastole. Then
in examining the heart, when the lungs are being alter-
nately filled and emptied, partly covering the organ at each
expansion, its apex only is seen, and it seems to retract
when the heart contracts. In order to demonstrate the
period of contraction in systole of the ventricles, I have
employed the proceeding of Harvey, pushing a small sil-
ver tube through the walls of the heart into the left ven-
tricle, withdrawing the stylet; and at each systole, a small
jet of blood is forced through the tube, which enables one
to determine at a glance when it takes place. In order to
determine the period of elongation and shortening of the
heart, I have devised an apparatus by means of which this
phenomenon is exaggerated.*

In reasoning from the action of the heart in the lower
animals to the corresponding movements in man, one should
take into consideration the similarity in structure and ar-
rangement of the organ and also take care that the ordi-
nary conditions of life should approximate as nearly as
possible to those in the human subject. For this reason,
the most valuable experiments are on the warm-blooded
animals; and the phenomena found here are not always
verified in animals lower in the scale. I have not touched
upon the change in form of the heart in the cold-blooded
animals in the body of this paper; for although such inves-
tigations are interesting in themselves, they do not teach
much in regard to human physiology. I may here state,
however, that in the turtle the heart shortens during sys-
tole. This is due to the thinness of the ventricle and the
great size of its cavity compared with the warm-blooded
animals. The heart of the frog, also, shortens slightly dur-
ing systole, and I have been able to measure the actual
extent of shortening with a pair of ordinary dividers. An
American observer f has described an experiment, which

* Since the publication of this article in 1861, I have become convinced, by
a number of more exact observations on the exposed heart, that the ventricles
shorten during their systole. I have therefore omitted the wood-cut and de-
scription of the apparatus which I devised and which seemed to show elonga-
tion of the ventricles.

t Dalton's " Treatise on Human Physiology," 2d edition, p. 258.

70 ACTION OF THE HEART AND RESPIRATION

I have often repeated, to prove the elongation of the frog's
heart dnring contraction, which consists in holding the
heart by the base between the thumb and finger, with the
apex upward, and irritating it with the point of a needle.
At each irritation the apex is elevated, giving an appear-
ance of elongation. This appearance is not deceptive; the
heart actually elongates, but the position in which it is
held, the ventricle being empty, causes its flaccid walls dur-
ing relaxation to collapse, shortening the heart more than
is natural. The same experiment I have repeated with
the heart of the turtle; but in altering the position of the
heart and allowing the apex to hang downward, the heart
wall be found to shorten during the systole, the dependent
apex being drawn up by the muscular contraction. These
experiments prove nothing one way or the other. It is
better, in all experiments of this description, to observe
the heart in situ, while its cavities are filled with blood. In
observations upon the irritability and various properties
of the anatomical elements of the heart, phenomena in
cold-blooded animals may be studied with advantage; for
here the properties are the same, modified only by the vital
condition of the animal, which, by diminishing the intensity
of their manifestations, render their study more simple.

The following experiments were made in regard to the
change in the length of the heart during the systole or
contraction:

Experiment I. January 28, 1861. — A good-sized dog was poi-
soned with curara, artificial respiration was kept up, and the heart,
which was beating strongly and naturally, was exposed in the usual
way. Upon holding the base of the heart between the index and
middle fingers, the thumb, placed upon the apex, was sensibly raised
at each systole, which was marked by the hardening of the ventri-
cles. The mekeoscope * was now applied and indicated elongation
with every systole, or contraction of the ventricles. The systole
of the heart was also marked by slight corrugation of the surface
of the ventricles, by a tilting movement of the apex upwards and
from left to right and by a twisting movement of the heart on its
axis, from left to right.

Experiment II. February i, 1861. — A medium-sized dog was
etherized and the heart exposed in the usual way. The facts which
are recorded in Experiment I were demonstrated upon this animal.
The mekeoscope was applied to the heart, which was acting nor-

* The instrument designed to show elongation of the ventricles, the descrip-
tion of which has been omitted.

ACTION OF THE HEART AND RESPIRATION 71

mally, and indicated elongation during the systole. This point was
verified by several medical gentlemen. The upper extremity of the
indicator moved one-half an inch to an inch with every beat of
the heart. It was determined that the heart elongated during the
systole, by introducing a small silver canula into the left ventricle
and noticing that the indicator showed elongation every time a jet
of blood was forced through the canula.

Experiment III. February 8, 1861. — A large dog was poisoned
with curara and the heart exposed in the usual way. The heart was
pulsating well ; the mekeoscope was applied, and elongation during
the systole was demonstrated. The various points recorded in Ex-
periment I were confirmed in this animal.

Experiment IV. February 15, 1861. — A medium-sized dog
was etherized and the heart exposed in the usual way. The mekeo-
scope was applied and the points recorded in the preceding experi-
ments were confirmed.

Experiment V. February 19, 1861. — A good-sized dog was
etherized and heart exposed in the usual way. The points recorded
in the preceding experiments were confirmed in this.

Conclusions. — From the five observations here re-
ported, which I have repeatedly confirmed in unrecorded
experiments, there is one legitimate conclusion; viz., that
the heart of the dog elongates during the systole, or con-
traction of the ventricles. In reasoning from the inferior
animals to the human subject, taking into consideration the
anatomical characters, it is found that the heart in the dog
has essentially the same anatomy as in man; but instances
are on record where the heart has been exposed to observa-
tion in the human subject. Harvey states, in his report of
the remarkable case of the son ofthe Viscount Montgomery:

" We also particularly observed the movements of the heart,
viz., that in the diastole it was retracted and withdrawn, while in
the systole it emerged and protruded ; and the systole of the heart
took place at the moment the diastolic impulse in the wrist was
perceived : to conclude, the heart struck the walls of the chest, and
became prominent at the time it bounded upwards and underwent
contraction of itself." *

Haller states that in the case of ectopia cordis which
he had an opportunity of observing, the heart shortened
during its systole, as it did in animals that he examined.
Both of these physiologists had the opportunity of exam-
ining the action of the heart in the human subject, and
both verified their previous observations on animals, al-
though the results were contradictory.

* Harvey's Works, published by the Sydenham Society, page 384.

72 ACTION OF THE HEART AND RESPIRATION

It seems, then, a legitimate conclusion that in man, as in
the animals examined, the heart elongates during its systole.

Having come to this conclusion from actual observa-
tion, the next step is to endeavour to account for it by
the anatomical arrangement of the muscular fibres of the
heart. This can easily be done; for if a heart is boiled so
as to dissolve the areolar tissue which holds together its
muscular bundles, the fibres can easily be separated and
traced. On the outside is a layer of fibres, common to both
ventricles, taking a spiral course from left to right, from
the base to the apex. Removing these superficial fibres,
beneath them is found a mass of circular fibres, enveloping
separately the right and left ventricles. The action of these
circular fibres in shortening is, of course, to increase in
diameter; and this increase in diameter, from the arrange-
ment of the fibres, would produce elongation of the body
of the heart.

The powerful action of these deep circular fibres of the
heart is also shown by a phenomenon noticed during con-
traction; namely, the production of rugae on the surface
of the ventricles. This appearance is not mentioned by
Harvey but is noticed by Haller in the work I have before
quoted, vol. i., page 389.

" Quando cor quietum, aut relaxatum, a stimulo quocunque in
motem cietur, tunc apparent in externa cullis superficiae rugae, in
quas fibrae contractae crispantur, undulatae, in rana et anguilla evi-
dentur transversae, neque in cane, fele, aut aliis calidi sanguinis
animalibus obscurae."

This may be because the superficial fibres, being ex-
posed to the air, are more irregularly and less powerfully
contracted than the deep, or it may be a phenomenon
which always takes place. At all events, it indicates that
the powerful contraction of the deep circular fibres throws
the superficial fibres into slight longitudinal folds from the
greater efBciency of their action; and that the superficial
fibres, which from their arrangement might tend to short-
en the heart, do not compress, in their contraction, the
deep fibres, but that the latter are the more powerful agents
in the systole. Thus what is demonstrated by observation
of the action of the heart in the living animal may easily
be accounted for by the anatomical arrangement of its
muscular fibres.

ACTION OF THE HEART AND RESPIRATION 73

In regard to the hypothesis of Bassuel, which is so
often quoted, that elongation of the heart, by putting the
chordae tendineae on the stretch, would prevent the closure
of the auriculo-ventricular valves and therefore is impos-
sible, I have nothing to say. It seems to me sufficient to
have demonstrated on the living animal the elongation;
and I have this simple fact to oppose to any hypothet-
ical objection.

Cause of the Rhythmical Contractions of the
Heart. — The cause of the regular and intermittent con-
tractions of the heart is obscure; and the experiments that
I have made on this subject, though far from being so satis-
factory as the preceding, still, I conceive, define the extent
of actual knowledge and bring to light some laws which
regulate the action of this organ. It was first supposed
that the blood circulating through the heart was the cause
of its rhythmical contractions; but the heart will continue
to beat regularly after it has been emptied of blood and
has been removed, indeed, from the body. The atmosphere
was then supposed to supply the place of the blood as a
stimulus; but the heart of a frog has been placed under the
receiver of an air-pump and still it continued to pulsate.
Without going farther into the opinions now entertained
by physiological writers, it is sufficient to state that physi-
ologists are not yet fully acquainted with the real cause of
the rhythmical contractions of the heart; and the follow-
ing experiments were made in the hope of throwing some
light upon this obscure subject.

Experiment VI.* November 14, i860. — An alligator, six feet
in length, was poisoned with curara, the thoracic cavity opened
and the heart exposed. Some experiments were then made upon
this organ which will be detailed in another place ; but, twenty-four
hours after the operation, the heart, which had been left in situ,
was found beating regularly and with considerable force.

Experiment VII. January 28, 1861. — An alligator of the same
size as the one used in Experiment VI. was poisoned with curara,
the chest opened and observations made upon the heart. The heart
was left in situ and twenty-four hours after death was found pul-
sating vigorously and regularly. The auricles were then stimulated
with an ordinary magneto-electric apparatus during the intervals
between the movements of the organ ; they immediately contracted,
and their contraction was immediately followed by contraction of

* For the anatomy of the heart of the alligator, see Appendix.

74 ACTION OF THE HEART AND RESPIRATION

the ventricles. Upon applying the stimulus to the ventricles they
contracted, contraction of the auricles following immediately.
These phenomena were repeatedly verified in the presence of two
assistants ; the same results followed irritation with the point of a
scalpel. The heart was then removed from the body and emptied
of ijlood. When placed upon the table it pulsated quite rapidly
(about ten times i)er minute instead of four or five) but its con-
tractions were feeble. On stimulating the ventricles, they con-
tracted powerfully, feeble contractions of the auricles following.
On stimulating the auricles, they generally contracted feebly and
sometimes no movement was excited; but the ventricles contracted
invariably.

The aortic (there are two in the alligator) were then tied and
the heart was filled with blood (which was prevented from coagu-
lating by the addition of a little solution of carbonate of soda) by
injecting it through the right auricle and confining it with a liga-
ture. The heart then began to contract regularly and forcibly. The
auricles contracted first, and then the ventricles, making about four
pulsations per minute. The contractions were powerful and regu-
lar, contrasting strongly with the rapid and feeble action before
the organ had been filled with blood. The heart was evidently
over-distended, but was relieved by dividing the coronary artery,
allowing some of the blood to escape, until it was reduced to about
its normal condition of fullness. Electric stimulation of the auri-
cles excited contraction, followed by contraction of the ventricles,
and the same stimulus applied to the ventricles excited contraction,
followed by contraction of the auricles, in about the same manner
as when these experiments were made upon the organ before its
removal from the body. This, also, was repeatedly verified. The
heart was then emptied of blood and placed upon a clean plate.
The contractions became such as were noted immediately after the
heart had been removed from the animal and before it had been
filled artificially with blood.

The heart was then filled v^^ith water. The contractions were
not so powerful and regular as when it had been filled with blood,
and were limited chiefly to the ventricles. They were also much
more rapid. It was impossible to establish the contraction of the
auricles on electric stimulation, followed immediately by contrac-
tion of the ventricles, and the reverse, as when the heart was filled
with blood. The ventricles, still filled with w-ater confined in their
cavity, were then firmly grasped in the hand so as to subject the
muscular fibres to powerful compression. From that time the heart
entirely ceased its contractions and became hard, like a muscle in
a state of cadaveric rigidity. The experiment was then terminated
twenty-eight hours after the death of the animal ; and the heart
was still beating until its pulsations were arrested in the manner
described.*

Experiment VIII. On Turtles. — The hearts of turtles were

* These observations were begun twenty-four hours after the death of the
animal.

ACTION OF THE HEART AND RESPIRATION 75

exposed and removed from the body while pulsating. Electric
stimulation applied to the auricles produced contraction, followed
by contraction of the ventricle ; and a stimulus applied to the ven-
tricle produced a contraction, followed by contraction of the auri-
cles. This took place whether the irritation was electric or me-
chanical, like the point of a needle, and indifferently whether the
heart was removed from the animal or left in situ.

These observations were repeatedly verified upon the same
turtles and in a number of subsequent experiments.

Experiment IX. March 11, 1861. — The heart of a turtle was
removed and the ventricles separated from the auricles. The auri-
cles contracted spontaneously and regularly for twenty minutes, the
time during which their movements were observed ; and the ven-
tricle contracted irregularly and at intervals of two minutes or
more. The ventricle always contracted when irritated with the
point of a needle.

In this experiment I was not certain that the ventricle con-
tracted without the application of a stimulus, for it was exposed
to currents of air, jars of the table, etc., which might be capable
of producing contractions.

Experiment X. March 13, 1861. — The heart of a turtle was
removed from the body while it was beating regularly, and the
ventricle was separated from the auricles as in the preceding ex-
periment. Both auricles and ventricle were then placed under a bell
glass and carefully observed for an hour and thirty minutes.

When placed under the bell glass, the auricles contracted regu-
larly twelve to sixteen times per minute. No contraction of the
ventricle occurred.

Five minutes after. — Auricles the same and the ventricle con-
tracted once.

Seven minutes after. — Auricles contracting regularl}^ sixteen
per minute, ventricle contracted. (The apparatus was shifted from
one table to another, which might have been the cause of the ven-
tricular contraction.)

Ten minutes. — Auricles the same and ventricle contracted.

Eleven minutes. — Ventricle contracted.

Twelve minutes. — Ventricle contracting regularly five times in
two minutes.

Twenty-two minutes. — Ventricle contracting regularly seven
times in two minutes ; auricles contracting twenty-two times per
minute.

Thirty-two minutes. — Ventricle contracting four times per
minute; contractions of auricles rapid but irregular.

Forty-two minutes. — One and three-quarter minutes between
the contractions of the ventricle.

One hour and thirty minutes. — Auricles contracting eight times
per minute ; two minutes between the contractions of the ventricle.

Experiment XI. INIarch 13, 1861. — The heart of a turtle was
removed and placed under a bell glass.

Thirty minutes after. — It pulsated twelve times per minute,
contraction of the auricles always preceding that of the ventricle.

76 ACTION OF THE HEART AND RESPIRATION

Sixty minutes. — The heart pulsated six times per minute, the
auricles contracting first.

In making these experiments, it was found that the operation
of removing and dividing the heart produced a shock which inter-
fered at first with its action. The heart recovered from it, however,
in about thirty minutes.

ExpERiiMENT XII. February 15, 1861. — A medium-sized dog
was etherized and his heart exposed in the usual way, artificial
respiration being kept up. While respiration w^is being actively
performed by means of bellows and while the heart was pulsating
vigorously, the organ was suddenly removed from the body by a
single sweep of the knife. It was immediately placed upon the
table and contracted so vigorously that it bounded up at every
pulsation like an India-rubber ball. This remarkable phenomenon
lasted for a few seconds only, but the heart pulsated regularly for
two minutes. A powerful shock was then passed through it by
means of a magneto-electric apparatus, with the effect of imme-
diately arresting all regular pulsations ; but this was followed by
a general, irregular vermicular action of the fibres. This continued
for thirty minutes. At first irregular contractions could be excited
by feeble currents; but after thirty minutes this became impossible.
When the vermicular action of the muscular fibres had ceased no
contraction could be excited by electric or mechanical stimulus.

Experiment XIII. March 13, 1861. — A turtle was poisoned
with a variety of curara which arrests or depresses the action of
the heart, by injecting about a grain of it in solution under the skin.
In thirty minutes the animal was dead and the exposed heart was
found beating feebly and slowly. On applying electricity to the
exposed muscles, their irritability was found, by actual comparison
with the exposed muscles of turtles which had not been poisoned,.
to be very much diminished.

Experiment XIV. March 13, 1861. — The preceding experi-
ment was repeated upon another turtle. When all signs of life had
disappeared, the heart was exposed and found beating feebly^
Muscular irritability was much diminished.

It will be seen by these few experiments that it is diffi-
cult, if not impossible, in the present state of knowledge
and with such data alone, to say why the heart contracts
in the manner which is characteristic of it. If the cause
resides in the nervous system, it must be in nerve-centres
existing in the substance of the organ. In short, the con-
traction of the heart is dependent either upon nerves in
its substance or upon an inherent property peculiar to its
muscular fibres. The nervous influence, if there is any,,
must come from the sympathetic or organic system, be-
cause an organ must remain connected with the cerebro-
spinal centres in order that any influence should be derived
from this system.

ACTION OF THE HEART AND RESPIRATION 77

Dr. Robert Lee, of London, has demonstrated the ex-
istence of sympathetic ganglia in the substance of the
heart ; but it is impossible to say positively that an influence
derived from these is the cause of its rhythmical contrac-
tions. The most that can be said on this subject is that
the muscular fibres of the heart have an inherent property
of contraction so long as they are in a state of physical and
chemical integrity; that this contraction, like that of all
other muscles, is followed by a relaxation; but the fibres of
the heart, after the short period of repose which is thus
allowed them, contract again. I know that in this state-
ment I am simply describing the phenomena of the heart's
action and confessing ignorance as to its cause; but we are
in the best position to acquire information upon any sub-
ject when admitting the real state of knowledge, and not
attempting to explain what, with our resources, is incapable
of explanation.

I have given the sum of actual knowledge of the cause
of the heart's action as an introduction to a study of some
of the properties of the muscular fibres of this organ and
the laws by which their contractions are regulated.

L The muscular fibres of the heart possess in a remark-
able degree that property known as irritability. This is
more marked in the auricles than in the ventricles. The
auricles contract readily upon the application of a stimulus
applied to the surface; and Virchow has demonstrated that
the internal surface is much more irritable than the ex-
terior.

IL It has been shown by experiments made by Erich-
sen * that the action of the heart is arrested in about thirty
minutes, in the warm-blooded animals, by ligature of the
coronary arteries, artificial respiration being continued,
showing that the presence of a certain quantity of blood
in the substance of the organ is necessary to the irrita-
bility of its muscular fibres.

in. Experiments here detailed, as well as those of other

* These experiments were made by pithing the animal, keeping up artificial
respiration and opening the chest. It was found that the heart continued to
beat under these conditions, for one to two hours, but was arrested in a short
time if the coronary arteries were ligated. The mean of six experiments showed
the duration of the heart's action, after ligation of these vessels, to be 23^
minutes. The experiments are to be found in the " Medical Gazette," July
S, 1842.

78 ACTION OF THE HEART AND RESPIRATION

observers, show that the heart of cold-blooded animals,
especially the alligator, retains its irritability for a long-
time after death. In Experiment VII. the heart was beat-
ing twenty-eight hours after death, when its action was
artificially arrested. This was due in part to the action
of curara; for Bernard has lately shown that muscular irri-
tability remains in frogs poisoned with this agent much
longer than ordinary, and that the action of the heart is
also prolonged.* This property renders curara valuable
in studying the movements of the heart.

IV. The same experiments (on turtles and alligators)
show that a stimulus, mechanical or electric, applied to
one part of the heart is propagated to the other, and also
tend to show that the stimulus which, in the natural action
of the organ, excites the auricles to contraction, is propa-
gated from them to the ventricles. These experiments are
not new. The same fact has been noticed by Mr. Paget
in the heart of the turtle and was published in the " British
and Foreign Medico-Chirurgical Review," vol. xxi., p. 550.

V. Experiments IX. and X. show that the irritability
of the auricles and ventricles are separate and distinct; that
the auricles possess this irritability in a much greater de-
gree than the ventricles, as demonstrated by the distinct
contractions of auricles and ventricles when separated
from each other and the much greater frequency of con-
tractions of the auricles; that the contraction of the auri-
cles acts as a stimulus to the ventricles, for when they are
left together, as in Experiment XL, and the heart is re-
moved from the body, the auricles always contract first,
and their contraction is invariably followed by contraction
of the ventricles.

VI. Experiment VII. shows that the heart of the alli-
gator, if emptied of blood, does not contract regularly;
but that its regular contractions return if the blood is in-
jected into and confined in its cavities; also that the propa-
gation of a stimulus from auricles to ventricles is not inva-
riable in the heart emptied of blood, but that it may always
be demonstrated in the heart filled with blood either natu-
rally or artificially.

VII. The same experiment shows that the heart filled

* Bernard, " Substances toxiques et medicamen tenses," page 320 ef seq.

ACTION OF THE HEART AND RESPIRATION 79

with water does not act normally after removal from the
body, as it does if blood is injected into its cavities, but
more rapidly and less ef^ciently; and finally, that powerful
compression seems to paralyze the muscular fibres instant-
ly and cause them to take on cadaveric rigidity.

VIII. Experiment XII. shows that a powerful electric
shock passed through the substance of the heart, in warm-
blooded animals, immediately arrests its regular pulsa-
tions.

IX. Agents which abolish or diminish general muscular
irritability, like the sulphocyanide of potassium, have a cor-
responding effect upon the heart. This is a fact now well
established.

Experiments XIII. and XIV. show that a certain kind
of curara, which arrests the action of the heart, diminishes
very much the general muscular irritability.

Conclusions. — From the facts stated above, the fol-
lowing deductions can legitimately be made:

The natural stimulus of the regular movements of the
heart is the blood; and this stimulus can not be adequately
supplied by any other fluid of less density, like w^ater;
so that, in conditions in which the blood becomes watery,
as in the reaction after copious bleeding or in an?emia, the
contractions of the heart are feeble and rapid; and in affec-
tions in which the blood becomes denser than in health,
as in plethora, the heart contracts more slowly and with
abnormal force.

In the normal action of the heart, this stimulus first
affects the auricles, which are first distended with blood,
and is propagated thence to the ventricles.

All irritability of the muscular fibres of the heart may
be immediately arrested by forcible compression; and its
property of regular contraction may be abolished by a
powerful electric current.

A peculiarity of the muscular irritability of the heart is
that when the organ has ceased to contract spontaneously
while in the chest or after removal from the body, contrac-
tions can not be excited by ordinary stimuli, such as irri-
tation with the point of a needle or scalpel or electricity;
while such irritation applied to any of the muscles will pro-
duce contractions. In an experiment which I made on

So ACTION OF THE HEART AND RESPIRATION

this point upon the heart of a dog, I found that the heart
ceased beating- in about ten minutes after the stoppage of
respiration (the dog had been etherized and his heart ex-
posed), and that after that time electric stimulation ap-
plied to the heart failed to produce contraction, although
the sterno-mastoid and muscles of the chest, which had
been exposed during the operation, contracted powerfully
on the application of the stimulus. This favors the idea
that the muscles of the heart differ from the other striped
muscles in possessing the inherent property of regular
contraction; for they continue to contract till they have
lost their irritability, and then can not be excited to action
artificially. This is true only when the heart is allowed
to stop spontaneously and the duration of its pulsations
is not interfered with by placing it in a vacuum (which,
while it does not arrest, abridges the duration of the heart's
action) or by other means.*

The irritability, which in ordinary muscles is manifested
by their contraction upon the application of a stimulus,
and, in the case of the heart, by regular pulsations so long
as the fibres retain their integrity, is really identical in the
heart and general muscular system; it is greatest in the
heart and is much greater in the auricles than in the ven-
tricles, as shown by experiments. In the heart this irrita-
bility becomes extinct before general muscular irritability
is lost, for the regular contractions of the organ after death
or after removal from the body wear it out, while the gen-
eral muscular system, if unstimulated, is in a state of re-
pose. It is also true that muscular, like nervous irritabil-
ity, disappears soonest in parts where it is most intense,
as it does in animals like the warm-blooded, the functions
of which are most active. The ventricles seem to depend
for their stimulus upon the contraction of the auricles; for
when separated, as in Experiment X., the ventricles do not
contract so frequently as the auricles, or so frequently as
when their connection with them is not severed. The ven-

* I have not made a sufficient number of experiments to be able to state
this positively, but it is certain that the general muscular irritability continues
long after the heart has ceased to beat ; and the question arises, in studying the
heart of a cold-blooded animal in a quiescent state, but contracting upon irrita-
tion, whether it does not contract spontaneously but at remote intervals, as in
Experiment X. This question can be answered only by more extended obser-
vations.

ACTION OF THE HEART AND RESPIRATION 8i

tricles possess, then, an independent irritability which is
much less than that of the auricles.

The irritability of the heart is like the general muscular
irritability in another respect. Most agents which para-
lyze the muscular system paralyze the heart; and Experi-
ments XIII. and XIV. show that the peculiar variety of
curara, which acts upon the heart, diminishes to a great
extent the irritability of the general muscular system. On
the contrary, the most common variety of curara, which
paralyzes the motor nerves and the sympathetic system,
leaves the muscular irritability intact, and also the move-
ments of the heart, which will continue for a long time after
death, if respiration is artificially performed.

Mechanical Causes which arrest the Heart's
Action. — In asphyxia and in some organic diseases of the
heart, there is arrest of the action of this organ. When
this is caused by mechanical obstruction, as in disease at
the aortic orifice, death is attributed to overdistension of
the heart; but in asphyxia it becomes a question whether
death is due to this cause or to the circulation of venous
blood in its substance, as was supposed by Bichat. In
experiments on the lower animals, when we expose the
heart and keep up artificial respiration, we can easily see
the immediate effects of arrest of respiration upon its
action. It becomes distended, changes from a red to a blue
color, showing that venous blood is circulating in its sub-
stance, and gradually its movements cease. But if respi-
ration is recommenced before its action has been entirely
arrested, it immediately becomes florid, its distension is
gradually relieved and soon its normal action is reestab-
hshed. In order to determine the cause of stoppage of
the heart in asphyxia, I made the following experiments.

Experiment XV. February i, 1861. — A dog was etherized
at 2.15 p. M. and the chest opened in the usual way. At 2.25 I
stopped respiration. In fifty seconds the heart became dark and
much distended. Respiration was recommenced, which had the
effect of soon restoring normal action. The pulmonary artery and
aorta were then tied suddenly with a strong cord. The heart be-
came much distended, was of a red color, labored more than when
respiration had been stopped, and in forty seconds it became neces-
sary to remove the ligature for fear of permanently arresting its
action. After removing the ligature, the heart gradually returned
6

82 ACTION OF THE HEART AND RESPIRATION

to its normal condition, but more slowly than when respiration had
been arrested for fifty seconds.

At 2.40 a grain of curara was injected into the areolar tissue.
At 4.10 the aorta was compressed. The heart labored, and in twen-
ty-five seconds the compression was removed and it gradually re-
sumed its normal action. Respiration was then suspended with the
same effect on the heart. In one minute respiration was recom-
menced and the heart resumed its normal action.

In this experiment compression of the aorta and pul-
monary artery produced more trouble in the heart's action,
the trouble came on more rapidly, and it was longer be-
fore its action became normal than when respiration was
stopped; though when the vessels were compressed the
heart was florid, showing red blood circulating in its sub-
stance, and when respiration was arrested it became dark.

Experiment XVI. February 8, 1861. — A large dog was poi-
soned with curara and the chest opened in the usual way. Respi-
ration was stopped for two and a half minutes. The heart became
very dark, much distended, and labored ; but when respiration was
recommenced it became gradually relieved, and in a few minutes
regained its normal action. The aorta was then tied for two min-
utes. The heart remained red, became more distended, and la-
bored more than in the previous instance, but gradually resumed
its action after the ligature was removed. During the time that
the aorta was compressed, here, as in Experiment XV, respiration
was continued.

In this experiment I tried to ascertain how long the
heart could be kept distended by asphyxia or compression
of the great vessels and yet resume its functions when the
cause of the distension was removed.

Conclusions. — Great distension of the heart will pro-
duce paralysis of its muscular fibres; and this is the cause
of the arrest of its action in asphyxia and in many cases of
sudden death, not the circulation of venous blood in its
substance, as was supposed by Bichat. The experiments
which I have detailed demonstrate this fact in regard to
asphyxia; for here it is shown that the greater the dis-
tension the sooner the heart ceases its contractions. The
heart is arrested sooner by ligature of the great vessels,
when red blood circulates in its substance, than by arrest
of respiration, when it is supplied with black blood, because
in the first instance the distension is greater.

The mechanism of this muscular paralysis is the same

ACTION OF THE HEART AND RESPIRATION 83

as that of the paralysis of any striped muscle by straining.
If a muscle is violently extended, as in a dislocation, there
is loss of function for a period proportionate to the sever-
ity of the strain. The same is true in regard to the heart;
but the constant action of the heart is necessary to exist-
ence; and when this muscle is paralyzed by straining of its
fibres by distension, the animal dies before it has time to
recover its functions. In case of asphyxia, then, so long
as the heart continues to act, though feebly and at long
intervals, artificial respiration will probably restore Hfe;
but after its action has been suspended there can be little
or no hope of restoring it.

Cases of sudden death from organic disease of the heart,
contrary to the popular impression, are not common; and
the only form of this affection in which sudden death is
likely to occur is disease at the aortic orifice. In this form
of the affection, the heart is liable to overdistension from
any cause which increases the force and rapidity of its ac-
tion; and death results from stoppage of the heart, in the
same manner as when the aorta has been tied, as was done
in the experiments before detailed.

In death from injury to the head, as from apoplexy,
respiration is interfered with and distension of the heart
occurs in precisely the same way as when artificial respira-
tion is interrupted in experiments on the lower animals.
This is further illustrated by the experiments of observers
who stun the animals upon which they operate in order to
observe the action of the heart. If artificial respiration is
not immediately established, the heart ceases to act, from
distension, and the animal dies.

In death from poisoning by opium, the respiratory
muscles are paralyzed by the poison, and the heart ceases
to act in the same manner as in asphyxia from any cause.
It would then follow that if artificial respiration is kept up
until the power of the poison is exhausted and natural res-
piration is gradually restored, the life of the patient would
be preserved; and the well-known experiments of Sir Ben-
jamin Brodie with opium and curara have proved that this
is the fact.

In some cases of convulsions, when death occurs res-
piration is interfered with and the heart is arrested by over-
distension. This is true of all nervous diseases which, from

84 ACTION OF THE HEART AND RESPIRATION

their action upon the general system or upon the respira-
tory apparatus, produce death.

In death from introduction of air into the veins, the air
going to the right side of the heart is divided into minute
bubbles which can not pass through the lungs. The heart
becomes distended from this obstruction and ceases to con-
tract from overdistension.

It appears, therefore, that distension of the heart, by
its mechanical action on the muscular fibres, may cause
stoppage of the circulation and death; that sudden death
may generally be attributed to this cause; that the cause
of this distension may usually Ije referred to the respiratory
function; and that the indications are, therefore, to rees-
tablish this function, by artificial respiration or otherwise,
w'hen it is arrested, or to prevent the diseases under which
the patient may labor from interfering with it.

Influence of the Pneumogastric Nerve on the
Action of the Heart. — The heart, like other of the
striped muscles, is provided with nerves derived from the
cerebro-spinal system; but the action of the nerves which
go to the heart differs from the nervous influence exerted
upon any other muscle. If a nerve distributed to a vol-
untary muscle is divided the muscle is paralyzed; but after
division of the pneumogastric nerve, which is distributed
in part to the heart, this organ, far from being paralyzed,
is accelerated in its action. Bernard has found that di-
vision of the pneumogastrics in the neck increases the
number of cardiac pulsations, sometimes even doubHng
them; but that the force of the contractions is diminished.
When the peripheral end of a divided nerve going to a
muscle is faradized the muscle is thrown into violent con-
tractions; but stimulation of the peripheral ends of the
pneumogastrics arrests the action of the heart. These ob-
servations were made in 1845, by Weber, and have been
repeatedly verified by physiologists since that time; but the
cause of this peculiarity of action has not been satisfacto-
rily explained.

In the first place it is important to determine whether
the electric stimulus is conveyed to the heart directly
through the motor filaments of the pneumogastrics or
through the sensor}- filaments to the nerve-centres, and

ACTION OF THE HEART AND RESPIRATION 85

by reflex action operates through other nerves on the
heart. This is easily ascertained by dividing both pneu-
mogastrics and stimulating alternately the central and
peripheral ends; when it is found that the current applied
to the peripheral extremities will arrest the action of the
heart, while the same stimulus applied to the central ends
produces no such effect. By means of curara, the motor
nerves and the motor filaments of the mixed nerves are
paralyzed, the two systems being dissected out, as it were,
by this curious poison; and it is found that when the pneu-
mogastric nerves are stimulated in an animal poisoned by
this agent, it is impossible to arrest the action of the heart.
This fact was pointed out by Bernard * and has been re-
peatedly verified by myself.

If both pneumogastric nerves of a dog are isolated in
the middle of the neck and subjected to a feeble current,
the first effect upon the movements of the heart, when this
organ is exposed to view, is a diminution in the frequency
of its pulsations. If the current is then gradually increased
in intensity, the action of the heart is arrested; the heart
remains dilated instead of contracted, and it ceases to act
so long as the current is continued. When the current
ceases the heart soon begins to beat and in a few minutes
will have resumed its normal movements. This effect is
produced in most of the inferior animals and can readily
be shown in the frog, turtle, alligator and other cold-
blooded animals, which are well adapted to experiments
on the heart and on the nerves; but in birds, Bernard has
not been able to demonstrate it; f for what reason, he does
not state. When the current is applied directly to the
heart, as I have done in some instances after the organ has
been removed from the chest, if the current is suf^ciently
powerful, all regular pulsations cease and there is nothing
but the irregular vermicular action which is observed when
the irritability of this organ has become nearly exhausted.
This fact I have observed in the heart of the dog.

Endeavoring to throw some light upon the cause of
arrest of the heart's action by stimulation of the pneumo-
gastrics, I made the following experiments upon the dog,
turtle and alligator:

* Bernard, " Substances toxiques et medicamenteuses," p. 348.

f Bernard, "Physiologie et pathologic du systeme nerveux," tome ii., p. 394.

86 ACTION OF THE HEART AND RESPIRATION

Experiment XVII. — The heart of a large dog was exposed in
the usual way while the animal was under the influence of ether.
After the chest had heen opened and while artificial respiration was
heing kept up, the pneumogastric nerves were isolated in the neck
and a feehle current was passed through them with the magneto-
electric machine used in former experiments.

The heart was arrested by quite a feeble current, in the man-
ner above described. This was repeated several times. The action
of the heart began again when the current was arrested.

Experiment XVIII. — The heart of a turtle was exposed and
found contracting regularly. The pneumogastric nerves were then
isolated in the neck and a feeble galvanic current passed through
thcni. This was done by bending the ends of the conducting wires
in the form of hooks and catching up each nerve. The action of
the heart was immediately arrested. It began again when the cur-
rent was interrupted and stopped when it was resumed.

Experiment XIX. March 13, 1861. — In a medium-sized dog
under the influence of ether the carotids and pneumogastric nerves
were exposed. The cardiometer was applied to the right carotid
and the following observations were made:

Arterial pressure (constant) (Minimum) 125 millimetres.

At each action of heart (Maximum) 130 "

Pulsations 5 "

The pneumogastrics were then divided. The movements of the
heart became more rapid and the instrument marked :

Arterial pressure (very variable) 100 to 150 miUimetres.

Oscillations with heart's action 2i "

The peripheral extremities were feebly stimulated. The action
of the heart became slower and the instrument marked :

Minimum 40 millimetres.

Maximum 65 "

Pulsations 25 "

The current was then stopped and the instrument marked :

Minimum I47i- millimetres.

Maximum 150 "

Pulsations 2^ "

Experiment XX. March 11, 1861. — The pneumogastrics and
carotids were exposed in a large dog in which the chest had been
previously opened and the heart exposed while the animal was
under the influence of ether. The cardiometer was applied to the
right carotid and marked :

Minimum 40 to 45 millimetres.*

Maximum 40 to 50 "

Pulsations 5 "

* When the chest is opened the pulsations become more frequent and the
pressure of blood is much diminished, as is seen by comparing these tables with
those in the preceding experiment.

ACTION OF THE HEART AND RESPIRATION 87

The pneumogastrics were then feebly stimulated. The pulsa-
tions of the heart were diminished in frequency and the instru-
ment marked :

Pulsations 20 to 30 millimetres.

Experiments XVII. and XVIII. demonstrate the ar-
rest of the heart's action by stimulation of the pnetmiogas-
trics in the dog and turtle. This fact is now established,
and the two experiments here recorded are introduced
merely to confirm previous observations.

Explanation of Illustration

The cardiometer is composed of a thick and strong glass
bottle, pierced by an iron tube securely soldered, and
having an opening (7") by which the mercury which
fills the bottle enters. One end of the iron tube is
closed, the other projects from the bottle and bends
upward in such a way as to receive at («') a glass tube
(7^) which is graduated and which is -1*2- to ^ of an
inch calibre.
At the upper part the bottle is hermetically sealed by a
cork pierced by a tube (/) of glass or iron, at the end
of which is adjusted a metallic tube (C) designed to
enter the vessel in which it is desired to measure the
pressure. The tube (C) is joined to the tube (/) by a
tube of India-rubber which should be very short.
When the instrument is in operation all of the upper part
of the apparatus {C e t) is filled
with carbonate of soda in order to
prevent coagulation of the blood.
The level of the mercury is (w) in
the bottle, and (;/') in the small
tube. This level corresponds to
zero, and when the blood presses
on the surface of the mercury the
pressure is communicated by the opening ( T) of the iron
tube and the mercury ascends in the graduated glass tube.
The length of the tube ( T) should be as great as 250 milli-
metres for powerful pressures. (Bernard, " Proprietes et
alterations des liquides de I'organisme, tome i., p. 167.)

Experiments XIX. and XX. show that when the pneu-
mogastrics are divided and the action of the heart is acceler-
ated its force is diminished as measured by the cardiometer;
and that w'hen the action of the heart is retarded by a feeble
current of electricity its force is correspondingly increased.
Both the arterial pressure and the pulsations are diminished
in Experiment XIX. by the administration of ether and
very much diminished in Experiment XX. by the operation

88 ACTION OF THE HEART AND RESPIRATION

of opening the chest; but my object was merely to ol)tain
the relative pressure and pulsations, and the effects of the
ether and opening the chest did not interfere with these
observations, in which I wished to show that when the pul-
sations of the heart were increased in number their force
became diminished, and vice versa.

The following experiments were made in order to de-
termine the influence of curara on this peculiar action on
the heart of electric stimulation of the pneumogastrics:

Experiment XXI. — A large dog was poisoned with curara
and the heart exposed in the usual way. The pneumogastric nerves
were then isolated and a current of electricity passed through
them. The apparatus was the one used in the other experiments;
and with the most powerful current that could be produced it was
impossible to affect the action of the heart. The animal had come
completely under the influence of the curara.

Experiment XXII. — A large turtle was poisoned with curara
at I p. M.^ and at 4 p. m. was quite dead. The heart was exposed
>and found contracting regularly. The pneumogastric nerves were
then isolated in the neck and a powerful current applied with the
machine before mentioned. It was impossible to arrest by this
means the action of the heart.

These experiments, like Nos. XVII. and XVIII., illus-
trate many others of a precisely similar character.

The experiments here detailed confirm the facts that
electric stimulation of both pneumogastrics will arrest the
movements of the heart and that curara so affects these
nerves as to abolish this action. This action of curara
on the motor filaments is similar to its action on other
motor nerves. Having an opportunity of operating upon
the alligator and wishing to repeat these experiments and
to observe, at the same time, the action of curara upon this
animal, I did so with the following interesting results:

Experiment XXIII. November 14, i860. — An alligator more
than six feet long was poisoned by the injection of about three
grains of curara under the skin of the hind leg. This curara was
of an inferior quality, and the dose was equal to about a grain of
that made use of in former experiments. In thirty minutes he
came sufficiently under its influence to be easily handled. The
chest was then opened and the heart, which was pulsating regu-
larly, exposed. The animal was quite dead by the time the dis-
section was finished. The pneumogastric nerves were then exposed
in the neck and the electric current was applied. The movements
of the heart were arrested so long as the current was continued

ACTION OF THE HEART AND RESPIRATION 89

and began again when it was interrupted. Artificial respiration
was kept up for some time, but this had no effect upon the action
of the heart and was done merely to exhibit the play of the lungs.
The animal was kept under observation three or four hours and
the foregoing fact was repeatedly verified.

Experiment XXIV. January 28, 1861. — The above experi-
ment was repeated upon another alligator of about the same size
as the first but poisoned with the best quality of curara. In mak-
ing the dissection for exposing the heart, a small nervous filament
going to the sterno-mastoid muscle was exposed, irritation of which
with the scalpel induced contraction of the muscle, though the
animal was quite dead. The pneumogastric nerves were exposed
and the heart's action arrested by a moderate electric current. The
animal was kept under observation more than three hours and
this point was repeatedly verified.

Twenty-four hours after, the heart was still beating vigorously
and could be arrested as before. The nervous filament going to
the sterno-mastoid muscle was stimulated, which produced slight
contractions of the muscle. Muscular irritability was very marked.

It is only in birds that experimenters have met with
any peculiarity in regard to the influence upon the heart of
electric stimulation of both pneumogastric nerves; and in
proportion to their elevation in the animal scale, it has
been difficult, and in most cases impossible, to arrest the
action of the heart by the means which will invariably pro-
duce this efifect in mammals, and more easily, even, in cold-
blooded animals. Nor have any animals been found able
to resist the influence of the curara upon the motor nerves,
with the exception of the alligator. These observations
should be extended to alligators of small size; but as yet
I have not been able to procure them.

When I first noticed the phenomenon which I have
described, I was at a loss to account for it; for the alligator
was motionless and insensible and the curara had been
tolerably prompt in its action, the animal coming under
its influence in thirty minutes to three-quarters of an hour
or an hour; which, in a large cold-blooded animal, where
the processes of life are languid, is as soon as one would
expect. In carefully reviewing, however, my observations,
I found that in the alligator the nervous system was much
less affected by curara than in other animals. In dogs the
motor nerves become entirely paralyzed and death takes
place by arrest of the muscles of respiration; while in the
alligator, when voluntary movement and the cerebral func-
tions are abolished so that the animal can be operated upon

90 ACTION OF THE HEART AND RESPIRATION

without the slightest difficiiUy, the motor nerves still re-
spond to stimulation. In Experiment XXIV. a nervous
filament was exposed during the operation and still re-
tained its irritability, as shown by muscular contractions
when it was irritated with the point of the scalpel. This
persisted and was marked, though in a less degree than
before, twenty-four hours after death. The properties of
the pneumogastrics remained with no sensible dimi-
nution.

It is evident that the motor properties of the pneumo-
gastric nerves, especially the branches distributed to the
heart, are more important to life than those of ordinary
motor nerves distributed to the general muscular system;
and it appears that this nerve is protected from disturbing
influences, like the action of poison, to a greater degree
than others. Evidence of this is seen in the various sources
from which the pneumogastric derives its motor filaments;
anastomosing, as it does near its origin, with the spinal
accessory, the facial, the sublingual and the first and sec-
ond cervicals. Not satisfied, however, with this purely
anatomical explanation, I endeavored to determine its pow-
ers of resistance to poisonous agents experimentally. To
do this I tried to find some means of retarding the ab-
sorption of curara, observing its effects upon the nerves
of the animal from the first, to determine whether its action
upon the general motor system precedes that upon the
pnevmiogastric nerve. For this purpose I made the fol-
lowing experiments, observations on the alligator not
being in themselves satisfactory:

Experiment XXV. February i, 1861. — A medium-sized dog
was etherized and the chest opened in the usual way. The opera-
tion was done at 2.15 p. m., and at 2.40 a grain of curara dissolved
in water was injected under the skin of the thigh. The sciatic
nerve and both pneumogastrics were then isolated and stimulated.
By this means, convulsive movements were produced in the leg and
the heart was promptly arrested by a feeble current.

At 3.10 the sciatic and pneumogastrics were stimulated, produ-
cing convulsions in the leg, not so marked as before, and arresting
the action of the heart.

At 3.40, one hour after the injection of the curara, the sciatic
was found inexcitable, but the heart could be arrested by stimu-
lation of the pneumogastrics, though it required a powerful cur-
rent. A weaker current diminished the frequency and increased
the force of its pulsations.

ACTION OF THE HEART AND RESPIRATION 91

At 4.10 the sciatic was still inexcitable but a powerful current
applied to the pneumogastrics arrested the action of the heart.

Experiment XXVL March 11, 1861. — One grain of curara of
an inferior quality dissolved in water was injected under the skin
of a medium-sized dog. Twenty-five minutes after, no effect being
produced by the first injection, a second grain was introduced. In
ten minutes signs of poisoning were manifested, the posterior ex-
tremities became partially paralyzed and the animal was placed
upon the operating table. The chest was then opened and the heart
exposed, the animal giving no evidence of pain. The pneumogas-
tric nerves were then isolated and stimulated, promptly arresting
the action of the heart. After the observation had been continued
for about thirty minutes the animal partially recovered from the
influence of the curara and made some voluntary movements.

Aided by these experiments, it is easy to understand
why, in the alHgator, stimulation of the pneumogastrics
continued to arrest the action of the heart when the ani-
mal had been poisoned with curara. The ahigator wheti
undisturbed breathes very slowly; and as in other cold-
blooded animals, pulmonary respiration is not necessary
to the movements of the heart. Curara seems, then, to
act first upon the brain, abolishing voluntary motion, be-
fore the motor nerves are paralyzed. This was demon-
strated in Experiment XXV. on the dog; for the effects
of the ether which was administered before making the
dissection were allowed to pass off, and the curara which
was subsequently administered abolished voluntary motion
long before the motor nerves were much affected, as dem-
onstrated by stimulation of the exposed sciatic. The gen-
eral motor nerves then slowdy came under its influence, and
last, the pneumogastrics, although their action on the heart
was not entirely abolished. By the means employed in this
operation, injecting the curara after the vital powers had
been enfeebled by opening the chest and exposing the
thoracic organs to the cold air, the dog was approximated
to the condition of the alligator.

• In Experiment XXVL, an inferior quality of curara
was employed, which apparently aboHshed sensation and
volition but had not sufficient power to entirely paralyze
the general motor nerves and had little or no effect upon
the pneumogastrics. The specimen used had the well-
known properties of ordinary curara but was deficient in
strength.

From these observations the followinp- seems to be the

92 ACTION OF THE HEART AND RESPIRATION

action of curara upon the nervous system: It affects voli-
tion and sensation, in whatever part of the central nervous
system these functions reside, and the motor system of
nerves. In regard to the order in which various parts are
affected, first, sensation and voluntary motion come under
its influence; then, the general motor system of nerves;
and last, as the preceding observations have demonstrated,
the motor filaments of the pneumogastric nerves, especially
those which affect the heart. By an ingenious series of
experiments with this substance upon frogs, Bernard has
demonstrated the fact that curara affects the motor nerves
exclusively, leaving the sensory filaments intact as well as
the muscular system. He has also shown that the sympa-
thetic system is paralyzed; for the abnormal heat and con-
gestion which are developed in the ear of the rabbit, for
example, when the sympathetic is divided, and which are
reduced to the normal standard when the cut extremity is
faradized, are abolished when the animal is put under the
influence of this agent.*

In the beginning of the section devoted to the influence
of the pneumogastrics upon the heart, I mentioned that
although the phenomena which follow stimulation of this
nerve are well established, no explanation of them has yet
been given which is generally accepted. Many theories
have been offered by physiologists, but it is not my object
to discuss them here. I shall endeavor simply to give the
actual state of knowledge on this subject, derived from the
experiments detailed in this essay and others which are
generally accepted.

I. The heart possesses in its ow-n fibres the property
of intermittent contraction, and the stimulus of the blood
passing continually through its cavities regulates to a cer-
tain extent its movements. This is shown by experiments
in the section on the " Cause of the Rhythmical Contrac-
tions of the Heart." Observations on the heart after sec-
tion of both pneumogastrics in the neck show that these
nerves further regulate the heart's action; for when their
influence is cut off, the pulsations of the organ become
rapid and feeble. This is shown in Experiment XIX., in

* For a full exposition of these facts, the reader is referred to Bernard's
" Le9ons sur des substances toxiques et medicamenteuses," and the "Phys-
iologic et pathologic du systeme nerveux."

ACTION OF THE HEART AND RESPIRATION 93

which the pneumogastrics were divided in the neck, in-
creasing the rapidity of the heart's action but diminishing
the force of its contractions, as indicated by the cardio-
meter. Many instances of palpitation of the heart un-
doubtedly may be referred to a deficiency in proper inner-
vation transmitted to it through the pneumogastrics; for
most of them are due to derangements of the nervous sys-
tem, and frequently these derangements have their origin
either in the lungs, from the individual being put " out
of breath " by exercise, or in the stomach, from indiges-
tion, both being organs abundantly supplied with filaments
from the pneumogastric nerves. The phenomena which
accompany palpitation of the heart are precisely those which
are produced by section of these nerves.

II. When the pneumogastrics in the neck are stimu-
lated, the electric current itself is not conducted by the
nerves, but there is a stimulus, resembling the ordinary
*' nerve force," which is conveyed to the muscular fibres of
the heart. It is difficult, when the irritability of the pneu-
mogastrics is unaffected, to regulate the stimulus so as to
observe the effects of sHght action of these nerves upon the
heart, its muscular tissue being extremely sensitive to irri-
tation of any kind; but by the action of curara, when it
partially paralyzes the nerves, as in the alligator, or in the
dogs used in Experiments XXV. and XXVI., it can be
shown that a slight stimulus diminishes the frequency but
increases the power of the contractions of the heart, w'hile
a powerful stimulus paralyzes the muscular fibres. Ex-
periments XIX. and XX. show that when the number of
the pulsations of the heart is diminished their force is in-
creased. If electricity is applied directly to the heart,
we can equally paralyze its fibres; and in this instance, if
the current is sufficiently powerful, this is permanent and
no further regular contractions occur. The heart, like
other organs, is subject to various changes in its nutrition;
and if it were not under the control of and regulated by
the pneumogastric nerves, it would be subject to variations
in its action which would seriously affect the general sys-
tem. A certain amount of nerve-force, like the " muscu-
lar sense " which produces tonicity of the muscular system,
is continually supplied to it by the cerebro-spinal system,
which regulates and moderates its action; this can be close-

94 ACTION OF THE HEART AND RESPIRATION

]y imitated by electricity; a slight current merely moderates
the action of the heart, but a powerful current, which repre-
sents the nerve-force in an intensely exaggerated form, ar-
rests its action completely. It is not surprising that an
organ which possesses such ])eculiarity in the properties
of its muscular structure and the proper action of which is
so important to the well-being and the life of the animal
should be thus guarded by the nervous system. There are
instances on record of immediate death by stoppage of the
heart from fright, anger, grief and other severe mental emo-
tions which operate powerfully on the nervous system.
Syncope from these causes is by no means uncommon. In
the latter instance, when the heart resumes its functions,
the nervous shock carried along the pneumogastrics has
been sufficient only to temporarily arrest the action of
the heart; in the former, when death is the result, the shock
has been so great that the heart is unable to recover from
its effects.

Mechanism of the Closure of the Valves of the
Heart. — The four ventricular orifices of the heart are pro-
vided with valves which permit the blood to flow in only
one direction. In some of the inferior animals the auricu-
lar orifices, by which the blood passes from the veins into
the heart, are provided with valvular apparatus. This is
the case in fishes; but in animals which have a double heart
and in man, the openings of the great veins into the right
auricle and of the pulmonary vein into the left auricle are
not provided with valves. These orifices are narrowed,
however, by the contraction of the fibres during the auric-
ular systole, moderating, though not entirely preventing
regurgitation; while the play of the auriculo-ventricular
valves permits the blood to flow freely in and fill the ven-
tricles. The ventricles then contract powerfully, close the
auriculo-ventricular valves, force open the semilunar valves
and project the blood, on the one side, into the pulmo-
nary artery, and on the other into the aorta; from whence
it is immediately prevented from regurgitating by the
closing of the aortic and pulmonary valves. Thus the
blood, forced into the right auricle from the veins of
the system, moves in but one direction toward the aorta
and is prevented from taking a backward course by

ACTION OF THE HEART AND RESPIRATION 95

the valves which protect the orifices of both ventri-
cles. It is correctly stated by physiological writers that
the tricuspid valves, unlike the mitral, do not always
completely close the right auriculo-ventricular orifice.
This may be observed in a very simple experiment.
Taking the fresh heart of any animal, the bullock, for ex-
ample, cutting away the left auricle and forcing water into
the ventricle with a syringe introduced into the aorta, the
aortic valves having been previously destroyed, it will be
seen that the mitral valve effectually prevents the flow of
the water through the auriculo-ventricular opening; and
the free borders of valves, the action of which may thus
be exhibited, are closely and effectually brought together
by the pressure exerted against them. But if an analogous
experiment is performed upon the right side of the heart,
cutting away the right auricle so as to expose the tri-
cuspid valves and injecting water against them through
the pulmonary artery, it will be seen that a slight regur-
gitation takes place and that these valves do not so effec-
tually close the auricular-ventricular orifice. Mr. T. W.
King, in an essay published in " Guy's Hospital Reports "
for 1837, pointed out the peculiarity of action of the tri-
cuspid valves and called it the " safety-valve function of
the right ventricle." He stated that it was a provision to
prevent congestion of the lungs when anything occurred
to obstruct the pulmonary circulation; and it is evident
that by this means, the delicate tissue of the lungs, in which
congestion can not be relieved by anastomoses as in the
general circulation, may be protected from injurious accu-
mulation or pressure of blood. The difference between
the action of these valves on the two sides of the heart I
have repeatedly verified, and it can be easily demonstrated
in the manner just described.

The next question which presents itself is the follow-
ing: By what means are the valves of the heart made to
close? This question may be easily answered in regard to
the semilunar valves. The blood circulates in the arterial
system under a pressure which will support a column of
about six feet of water or six inches of mercury. During
the flow of blood from the ventricle into the aorta, the
power of the heart overcomes this pressure and opens the
valves; but when the force of the heart is taken off, the

96 ACTION OF THE HEART AND RESPIRATION

valves are closed, effectually preventing regurgitation.
One would naturally suppose that the auriculo-ventricular
valves were closed in the same way, by backward pressure;
and this, indeed, is the general opinion; but in 1843, Baum-
garten endeavored to prove by experiment that these
valves are closed by a current in another direction, at-
tributing it to a contraction of the auricles and not the
action of the ventricles. I do not know that this view has
met with much favor, but some observers have confirmed
his experiments, and the explanation has been adopted
by Milne Edwards * and a few others. The experiments
upon which this view is based are briefly these:

The heart of a large warm-blooded animal is prepared
by completely removing the auricles so as to expose the
auriculo-ventricular valves. It is then held in a vertical
position, the valves lying in the cavity of the ventricles,
leaving the orifice patent. If water is poured slowly into
one of the ventricles through this opening, the valves will
gradually fioat out and their edges approximate; then,
when the ventricle is nearly filled, if the stream is suddenly
increased in power, the valves completely close.

The facts here stated are entirely correct, and I have
repeatedly verified them; but if, as before stated, a stream
of water is forced against the valves, the orifice is closed.
One can not, therefore, reason from the experiments of
Baumgarten that this is the natural mechanism of the clo-
sure of the valves, but it is necessary to examine the condi-
tions as they exist in the normal relations of the organ.
For that purpose, and with the object of settling this ques-
tion if possible, I carefully repeated the experiments of
Baumgarten and carried his observations a little farther.

Experiment XXVII. January 30, 1861. — In this experiment I
found that the mitral valves were closed when the current of water
poured into the ventricle flowed in a small stream. In this case
it is evident that they were closed by backward pressure ; for the
current of water, flowing thus in a bullock's heart prepared in the
manner above described, did not exert pressure upon the whole
of the auricular face of the valves, but merely made a small open-
ing for itself between them. I then used a larger stream, and in
this instance the valves were overpowered, and the water flowed
in a full stream from the aorta. The aortic opening was then

* Milne Edwards, " Lecons sur la physiologic et Tanatomie comparee de
rhomme et des animaux," tome iv., p. 30.

ACTION OF THE HEART AND RESPIRATION 97

closed and regurgitation took place freely at the auriculo-ventric-
ular orifice. In this modification of the experiment, however, the
force of the water was considerably greater than that of the natural
current of blood. It was impossible, indeed, to graduate this, and
to pour the fluid into the ventricle in a stream which would im-
pinge upon the entire surface of the valves, which did not flow
with considerable force. These facts were repeatedly verified in
this, and in confirmatory experiments which it is unnecessary to
detail here.

We may now consider the pressure of the blood in the
cavities of the heart during circulation; for it is evident
that when the auricle is entirely removed and water is
poured from a height into the ventricle, the experiment
is far from fulfilling the natural conditions, which it is so
necessary to observe in all physiological observations.
During the normal circulation, the veins, heart and arteries
are completely filled with blood; no air or gas can exist,
except in solution, in the circulatory system; and espe-
cially in the heart does the presence of any gaseous fluid
disturb the circulatory function. The blood, also, circu-
lates under a certain pressure; and a certain force is ex-
erted by the heart at every pulsation. In the arterial sys-
tem the pressure of the blood is represented by a column
of six inches of mercury. This pressure is nearly constant
in the arteries but is intermittent in the heart. In the heart
the pressure is nil during diastole, as has been shown by
actual experiment,* but nearly one-third greater than the
arterial pressure during its systole. In the venous system
the pressure is much less constant than in the arteries; it is
always less, and subject to frequent variations. Bernard
found the arterial pressure in the carotid of the horse,
measured by the cardiometer, to be no millimetres. At
each cardiac pulsation it was increased to lyS-f I^ ^^"
other horse he found the pressure in the jugular to vary
between 105, 100, 95 and 90 millimetres.:}: The pressure
exerted by the contraction of the auricles has not been
ascertained; and although it adds something to the venous
pressure, it can not be very considerable. Under these
conditions, during the diastole of the ventricles, the venous
pressure operates upon the auricular face of the auriculo-

* Bernard, " Le9ons sur les proprietes physiologiques et les alterations
pathologiques des liquides de I'organisme," tome i., p. 173.

f Bernard, ^/. n't., p. 172. | Bernard, oJ>. at., p. 203.

7

98 ACTION OF THE HEART AND RESPIRATION

ventricular valves, it has no cardiac pressure to oppose it
and the orifice is kept patent. The same is true during the
contraction of the auricles; the pressure is thereby in-
creased, it is exerted by a column of blood which impinges
upon the entire surface of the valves and the ventricles
are thus completely filled. During this time the blood is
prevented from regurgitating from the aorta and pulmo-
nary artery by the semilunar valves, which are closed by
the arterial pressure. But when the ventricles act, they
exert a force sufficient to overcome the arterial pressure,
which keeps the semilunar valves closed; and at the same
time they close the auriculo-ventricular valves, producing
one element of the first sound of the heart. The systole of
the ventricles ceases; its pressure is taken ofY; the arterial
pressure closes the semilunar valves, producing the second
sound; the venous pressure opens the auriculo-ventricular
valves, and keeps the orifice patent, until the succeeding
contraction of the ventricles. Thus it is that the cardiac
pressure, intermittent and operating during the systole of
that organ, being greater than the arterial and venous
pressure, at the same time opens the semilunar and closes
the auriculo-ventricular valves.

Inasmuch as Baumgarten's experiments showed that
the auriculo-ventricular valves, which are closed by means
of a backward pressure during the systole of the ventricles,
can be closed by pouring a stream of water into the ventri-
cles from the auricles, it occurred to me to extend these
observations to the aortic semilunar valves, and for this
purpose I made the following experiment:

Experiment XXVIII. January 30, 1861. — A bullock's heart
was prepared so as to show the action of the aortic valves; which
was done by cutting away a portion of the left ventricle so as to
expose them to view, securing the nozzle of a large syringe in the
aorta and forcing water toward the ventricular cavity. The semi-
lunar valves were thus closed, effectually preventing the passage
of the fluid. While the nozzle was yet in the aorta, diminishing
but not preventing the flow of liquid, water was poured from a con-
siderable height into the vessel. The valves were at first floated
out and then closed in the same manner as in Experiment XXVII.
on the mitral valves. This observation was repeatedly verified.

This last experiment would go as far to prove that
the semilunar valves are closed by a current from the ven-
tricle into the aorta, as the preceding one does that the

ACTION OF THE HEART AND RESPIRATION

99

current from the auricle to the ventricle closes the mitral
valves; yet, I venture to assert, no one could entertain for
a moment the view that the force which overcomes the
resistance of the aortic valves, by operating from the ven-
tricles, closes them by the same current. The experiment,
of course, proves nothing in regard to the action of the
valves at the aortic orifice, but it shows the falsity of con-
clusions drawn from experiments in which natural condi-
tions are so utterly disregarded as in those which favor
the idea that valves arranged for the purpose of permitting
the flow of blood in one direction and preventing reflux
are closed by the opposite current.*

Seat of the Sensation of the " Besoin de res-
pirer," which gives rise to the movements of res-
PIRATION.— The circulation of the blood is intimately con-
nected with the function of respiration. In health the
number of pulsations of the heart bears a definite relation
to the number of the respiratory movements; when the
pulse is increased in frequency, the breathing is more rapid;
and when the heart labors, as in cases of advanced disease
of this organ, the patient experiences a sense of suffoca-
tion which is not dependent upon the condition of the re-
spiratory organs. What gives rise to this sense of suffo-
cation? Why is it, when the lungs are unaffected and
when a large supply of pure air is taken in at every respir-
atoiy act, that a sense of suffocation attends imperfect
action of the heart ? These are questions which are of great
interest to the pathologist; but they can not be answered
without a knowledge of the seat of sensation of want of
air, which ordinarily is not perceived by the brain but in-
sensibly induces respiratory movements, and when circu-
lation or respiration is much disturbed, gives rise to the
distressing sensation of suffocation. To resolve these
questions, which are as yet imperfectly or incorrectly an-
swered by physiologists, is the object of this division of the
present paper.

Respiratory movements are regarded as reflex, a cer-

* Since this paper was written, I have seen a short article on the method
and time of closure of the auriculo-ventricular valves, by Dr. Halford ; but the
experiments seem to prove nothing beyond those here mentioned, being, indeed,
little more than repetitions.

loo ACTION OF THE HEART AND RESPIRATION

tain impression being conveyed to the respiratory centre,
followed by the action of the inspiratory muscles. This is
partly under control of the will; but under ordinary cir-
cumstances is involuntary. It is unnecessary to enter into
any discussion in regard to the seat of the respiratory cen-
tre. Physiologists now agree that it is situated in the me-
dulla oblongata at about the origin of the pneumogastric
nerves. Almost the same unanimity exists in regard to
the localization of the impression which gives rise to the
inspiratory acts; attributing it to an impression made upon
filaments of the pneumogastric nerves by the carbonic acid
in the air-cells. This is the view which was advanced by
Marshall Hall and which is now generally adopted; but
there are difficulties in the way of explaining all the phe-
nomena which are observed in health and disease on this
theory. In diseases of the heart there may be dyspnoea,
and yet the air be rapidly and efficiently changed in the
lungs. The evolution of a large quantity of carbonic acid
by the lungs, if it is promptly exhaled, does not produce
dyspnoea. In experiments upon the lower animals, which
are to be mentioned hereafter, phenomena are developed
for which such an explanation will not suffice. There are
some physiologists, indeed, who do not accept this ex-
planation of Marshall Hall; among them are Berard, who
locates the sense of want of air in the heart; * John Reid,
who thought that the respiratory movements were due to
the action of the black blood upon the medulla oblongata;
Volkmann and Vierordt, who thought that these move-
ments were reflex and due to the excitation of the general
sensory system of nerves by venous blood. This is a ques-
tion, however, which may be settled by direct experiment.
If a dog is rendered insensible by ether and the chest
opened, artificial respiration being kept up by a pair of
bellows, he will make no respiratory movements so long
as respiration is carried on artificially; but soon after res-
piration is stopped, the diaphragm, intercostals and other
inspiratory muscles, which are actually denuded and ex-
posed to view, will be seen to contract violently, this con-
traction, or effort at respiration, ceasing so soon as arti-
ficial respiration is resumed.

* Berard, " Cours de physiologic," tome iii., p. 523.

ACTION OF THE HEART AND RESPIRATION loi

An experiment analogous to this was performed in
1664, by Robert Hooke, in which he demonstrated that
respiratory efforts ceased in an animal so long as the requi-
site quantity of air was supplied to the lungs. In this ex-
periment he made an opening into the pleural cavity and
the lungs of a living dog and forced a current of air through
the trachea and out at the artificial opening. So long as
the current was continued the animal remained quiet; but
when it was interrupted he made efforts at respiration.
This experiment is made use of by Marshall Hall to sup-
port his doctrine of the reflex character of respiration, the
excitation coming from the lungs; for, he says, so long as
fresh air was supplied to the lungs there was no stimulus
for respiration and therefore no efforts were made; but
when this current ceased or when carbonic acid was sub-
stituted for atmospheric air, the contact of the carbonic
acid, which, in the one instance, was exhaled by the venous
blood, and in the other was introduced into the lungs, pro-
duced the excitation which was necessary to the respira-
tory act. This, however, is but a superficial view of these
phenomena. It is necessary to examine into the condition
of the heart and the rest of the circulatory system. It is
well known that the heart's action is dependent upon res-
piration and that an arrest of the interchange of gases in
the lungs is immediately felt by the circulation. It was for
the purpose of observing these conditions that the follow-
ing experiments were made:

Experiment XXIX. February 16, 1861. — A medium-sized
dog was etherized and the heart and lungs exposed in the visual
way. A pair of bellows was introduced into the trachea and arti-
ficial respiration kept up. So long as this was performed, the ani-
mal made no efforts at respiration, even after he had almost recov-
ered from the effects of the anesthetic; but when the artificial res-
piration was stopped, he soon began to make efforts to breathe,
as was indicated by contractions of the diaphragm and intercostals,
which were exposed to view. The femoral artery was then isolated
and divided, a ligature applied to the distal end. and the cardiac
end compressed with the fingers so that the blood could be permitted
to flow at will. A small stream was then allowed to escape, which
was of the brilliant red color of arterial blood, the animal remain-
ing quiet and respiration being kept up actively. Respiration was
then stopped, and the animal remained auiet until the blood be-
came dark in the exposed artery. He then, and not until then,
began to make eft'orts at respiration. Respiration was now resumed

I02 ACTION OF THE HEART AND RESPIRATION

and the blood gradually became red. The animal continued to
make efforts at respiration until the blood became red in the artery.
This observation was frequently repealed and the above phenome-
na were invariable. Since that time, also, I have repeated the ex-
periment upon other animals, always with the same result.

Experiment XXX. February 19, 1861. — A good-sized dog was
poisoned with curara and the chest opened in the usual way. When
the animal came fully under the influence of the poison he ceased
all respiratory movements. Artificial respiration, however, was
kept up for three hours ; and in about two and a half hours he
had so far recovered from the effects of the poison as to make
efforts at breathing when artificial respiration was interrupted.
The femoral artery was then opened and divided as in the former
experiment. When respiration was arrested the animal made ef-
forts to breathe, but only when the blood became dark in the artery,
and ceased these efforts when it became red again on resuming
respiration. This observation was made repeatedly.*

Experiment XXXI. February 15, 1861. — In a large dog un-
der the influence of ether, in which the heart was beating regu-
larly, the organ was suddenly cut from the chest. The animal
afterwards made several respiratory movements. In this instance
the " besoin de respirer " could not be derived from the heart, as
it had been removed from the body.

Experiment XXXII. March 11, 1861. — A good-sized dog was
etherized and the heart exposed in the usual way. Artificial respi-
ration was actively kept up, and while the heart was pulsating
regularly and vigorously, it was cut from the chest by a single
sweep of the knife. The lungs were still regularly inflated, but in
thirty seconds the animal began to make efforts at respiration,
which were continued for two and a quarter minutes. These ef-
forts were powerful and convulsive.

It would seem settled by these experiments, that the
" besoin de respirer," which is conducted to the respiratory-
centre and excites the movements of respiration, is not
situated in the lungs or in the heart but in the general sys-
tem; and the sense of suffocation is due to the presence of
black or venous blood in tissues which should be supplied
with arterial blood. One would therefore expect that this
peculiar sensation would, if it resided in the general sys-
tem, be conveyed to the nerve-centres by the ordinary
sensory nerves and not by the pneumogastrics, as was sup-

* This experiment has additional interest as confirming the well known ex-
periments of Brodie, in which he demonstrated that in poisoning by certain
substances, their eiTects will pass off if artificial respiration is continued for
a certain time. Among these poisons are curara and opium. Of course, in
this instance, it would have been impossible to preserve the life of the animal
after the chest had been opened and the thoracic organs exposed, but he evi-
dently recovered considerably from the effects of the poison.

ACTION OF THE HEART AND RESPIRATION 103

posed by Marshall Hall. This, indeed, is the fact, as is
shown by the following experiment:

Experiment XXXIII. February 15, 1861. — A medium-sized
•dog was etherized and the heart and lungs exposed in the usual
way. The occurrence of respiratory efforts when the blood be-
came black in the arteries and their cessation so soon as it regained
its red color were noted. The pneumogastric nerves were then
isolated in the neck and divided, producing the usual effect upon
the movements of the heart. The experiments of arresting artifi-
cial respiration and exciting respiratory efforts on the part of the
animal were then repeated with precisely the same effect as before
division of the pneumogastrics and as observed in other experi-
ments.

Although the sense which induces respiration is thus
located in the tissues and it is shown that it does not re-
side in the organs of respiration themselves, the cause of
this impression does not appear. The venous blood either
irritates the system from the presence of elements which
are not contained in the same proportion in arterial blood
or the tissues feel the want of some principle which the
venous blood does not contain in sufficient quantity. The
great difference between venous and arterial blood is in the
quantity of oxygen which they contain. According to the
latest experiments of Bernard in regard to the compara-
tive quantity of oxygen in arterial and venous blood, it
appears that the arterial blood of a healthy dog contained
18.28 parts of oxygen for every hundred parts of blood,
while venous blood contained only 8.42 parts of oxygen
per hundred.* In these experiments Bernard found that
when the gas was estimated by displacement with hydro-
gen or nitrogen, it became diminished if allowed to stand
a few hours, and that part of the oxygen became united
with carbon to form carbonic acid. He employed carbonic
oxide as a displacing agent, which prevented this change;
hence the large proportion of oxygen which he foimd in
both varieties of blood. The usual estimates are based
upon the experiments of Magnus and indicate in the arte-
rial blood of five animals (three horses and two calves)
separately examined, a mean of 2.44 per cent, of oxygen
for arterial, and 1.15 per cent, for venous blood, an esti-
mate very far short of the truth. The venous blood is sup-

* Bernard, " Le9ons sur les propri^tes physiologiques, et les alterations
pathologiques des liquides de Torganisme," tome i., p. 367.

I04 ACTION OF THE HEART AND RESPIRATION

posed by Brown-Sequard and others to be an active stimu-
lant to the tissues on account of its irritating properties;
but when it is shown that the arterial blood contains such
a large proportion of oxygen, which is indispensable to the
system and is contained in small quantity in the non-
arterialized blood, the immediate inquiry is as to whether
the excitation in question is due to the stimulating proper-
ties of the venous blood or the want of oxygen in the
tissues, which latter can be supplied only by arterial blood.
This question I conceive can be settled by experiment.
An animal does not feel the " besoin de respirer " while
artificial respiration is kept up actively; but he does soon
after this process is interrupted. In this case, partially oxy-
genated blood circulates in the arteries and is supplied to
the systemic capillaries. If it be that the tissues simply
need oxygen, any cause which w'ould prevent oxygen from
coming in contact with them would give rise to respiratory
movements, though there is no black blood in the arteries
and an abundant supply of fresh air is introduced into the
lungs. The following experiment bears upon this point:

Experiment XXXIV. February 19. 1861. — A good-sized dog-
was etherized and the chest opened in the usual way. Artificial
respiration was established and Experiment XXIX. verified. The
blood was then allowed to flow freely from the femoral artery
while artificial respiration was actively continued. While the blood
continued to flow the respiratory muscles were carefully observed.
During the first part of the bleeding, no respiratory efforts took
place ; but when the blood had flowed for a considerable time and
the system was becoming drained, respiratory efforts began, feeble
at first, but as the bleeding continued, becoming more violent until
the whole muscular system was affected with convulsive movements.

This experiment is of great interest and importance.
By the withdrawal of blood while respiration was active
the tissues were deprived of oxygen by a diminution in
the quantity of blood, and were relieved from the stimula-
tion of the black blood, if it has any stimulating properties,
for all the blood going to the capillaries was purely arterial
in character. No stimulation, then, was applied to the
tissues; they simply were deprived of their normal supply
of oxygen by a diminution of the oxygen-carrying fluid.
This gave rise to the " besoin de respirer," first to a slight
extent, but as the hemorrhage continued, increasing in
intensity till the whole muscular system was convulsed

ACTION OF THE HEART AND RESPIRATION 105

from the overpowering sense of suffocation; a sense which
is referred to the lungs but which really resides in the gen-
eral system.

These experiments give a new view of the " besoin de
respirer," which gives rise to the respiratory movements,
and of the sense of suffocation, which is incident to the in-
terruption of these movements. Alore and more as knowl-
edge of the functions of the body advances are certain sen-
sations which seem to come from special organs actually
located in the general system.

In treating of the sensation now under consideration
I am led to compare it with various others that are famil-
iar. The system needs periodical rest; it is undergoing
an incessant waste which must be supplied by food, and
a continual loss of fluid which must be supplied by water;
and it needs a constant supply of oxygen, which is furnished
by respiration. These are wants of the general system;
but their indications are referred to particular parts.
Drowsiness is indicated by drooping of the eyelids; hun-
ger, by uneasiness in the stomach; thirst, by dryness of the
mouth and fauces; and the " besoin de respirer " and sense
of suffocation, when respiration is interfered with, is re-
ferred to the lungs. But the sensation of hunger does not
reside in the stomach, though it may be momentarily ar-
rested by the introduction of substances, even of an indi-
gestible character, into its cavity. In a patient suffering
from any disease which is characterized by deficient diges-
tion and assimilation, while the system is capable of feeling
the want of nourishment, an abnormal appetite is a char-
acteristic symptom; and the hunger is not appeased for any
length of time by the introduction of food into the stom-
ach. This, as is well known to practical physicians, is a
frequent symptom of diabetes and chronic diarrhoea. Di-
rect experiments have been made upon the sensation of
thirst. Magendie and Bernard kept horses without water
for twenty-four or forty-eight hours, divided the oesopha-
gus so as to divert food and water from the stomach, and
then allowed them to drink. As fast as the water was swal-
lowed it flowed out at the wound; and though the mouth
and fauces were moistened, the thirst was not satisfied and
the animals continued to drink. Bernard has made similar
experiments on dogs in which he had established gastric

io6 ACTION OF THE HEART AND RESPIRATION

fistula}. These experiments 1 have frequently repeated,
and as they are very striking and easy of execution, I re-
port an example:

Experiment XXXV. November 17, i860. — A dog that had
been operated upon for the establishment of a gastric fistula two
days before was kept without water for twenty-four hours. At the
time of the experiment he was quite lively, having suffered little
from the operation. The cork was then removed from the tube in
the stomach and the animal was allowed to drink. He drank until
he desisted from actual fatigue, and after resting for a moment
drank again in the same way, the fluid all this time flowing freely
from the fistula. This was repeated several times until the animal
gave up the effort. The cork was then replaced in the tube, and
when the animal drank his thirst was soon satisfied.

These experiments, which are well known to physiolo-
gists, show that thirst is a sensation felt in the tissues but
referred to the mouth and fauces; and although these parts
and the walls of the stomach may be continually moistened,
the thirst is not appeased, nor can it be until the fluid has
been taken into the blood-vessels and circulates in the sys-
tem. This desire for liquids is always shown by animals
after the withdrawal of blood. I have repeatedly observed
animals from which I had removed blood by the jugulars
go to the water and drink copiously so soon as they were
set at liberty.

Conclusions. — Respiration is a reflex phenomenon
under ordinary conditions; and movements connected
with it are due to an impression conveyed from the general
system to the medulla oblongata, whence a stimulus is sent
out which animates the inspiratory muscles. While res-
piration is carried on efifectually without exertion on the
part of an animal, as in artificial respiration, evidently
no impression is made upon the respiratory centre, for no
respiratory movements take place.

The impression which excites respiratory movements
is received from the tissues and not from the lungs; for it
is only when dark blood instead of red is supplied to the
tissues, that the impression is conveyed to the respiratory
centre, producing eiTorts at respiration.

This impression is not transmitted through the pneu-
mogastric nerves but through the general sensory nerves;
for there is no difference in the manifestation of respira-

ACTION OF THE HEART AND RESPIRATION 107

tory movements when the supply of air to the hmgs is cut
off, if both pneumogastrics are divided.

This impression is due to the want of oxygen in the
tissues and not to stimulating properties of the venous
blood; for when the supply of oxygen is cut off by abstract-
ing blood from the system, the phenomena observed as
occurring during interruption of respiration are marked,
though air is supplied in abundance to the lungs.

This impression is not due to distension of the cavities
of the heart, as suggested by Berard; because the heart
may be removed from the body of a living animal and the
respiratory efforts will occur as in the case of abstraction
of blood.

This impression (the sense of want of air, " besoin de
respirer ") when exaggerated constitutes the sense of suffo-
cation; and it, like the sense of fatigue, of hunger or of
thirst, has its usual source in the general system, though it
manifests itself in the lungs in the same way that fatigue
affects the eyelids, hunger the stomach, and thirst the
mouth and fauces. They are all indications of wants of
the system and can not be effectually relieved by the local
effects of anything upon the organs to which they are re-
ferred by the sensations.

The necessity for respiration, or for oxygen, then, ex-
ists in the tissues; and asphyxia can not be solely applied
to arrest of the function of the lungs, but to anything which
interferes with the consumption of oxygen by the system.
Anything which operates in this way gives rise to a sense
of suffocation and afterward to general convulsions if it
is carried sufficiently far. Various pathological phenome-
na which would otherwise be obscure are thus explained.
The operation of simple asphyxia by tying the trachea or
preventing air from gaining entrance into the lungs in-
duces the sense of suffocation which first gives rise to re-
spiratory efforts more violent than ordinary, and subse-
quently, to general convulsions. All are familiar with
these phenomena however they may be explained.

In poisoning by carbonic oxide there are general con-
vulsions which arise from the sense of suffocation; for this
agent so operates upon the blood-corpuscles, that though
they continue red they are rendered incapable of perform-
ing their function of supplying oxygen to the system.

io8 ACTION OF THE HEART AND RESPIRATION

In poisoning by hydrocyanic acid, when the system
is not immediately overpowered by this agent and the mus-
cular irritability destroyed, the blood becomes incapable
of supplying oxygen to the system and convulsions ensue
as the result of the sense of suffocation.

In death by hemorrhage, convulsions, occurring just
before death, are invariable. This also is the result of de-
ficient supply of oxygen to the tissues, and the sense of
suffocation is the starting point. This was demonstrated
in Experiment XXXIV., in which the animal was bled to
death.*

Finally, in all cases where the supply of oxygen is cut
ofT, not from the lungs but from the tissues, a sense of
suffocation is the result, and convulsions ensue following
violent efforts at respiration.

Summary. — In the foregoing essay, I think I have
established the following facts, which are either not gen-
erally admitted or not vmderstood by physiologists:

I. That the heart elongates during the systole of its
ventricles. f

II. That the cause of the rhythmical contraction of the
muscular fibres of the heart is resident in the fibres them-
selves, is one of their inherent properties and remains so
long as they retain their " irritability."

III. That the normal stimulus which excites the regu-
lar and efficient movements of the heart is the blood, and
that this can not be replaced by a fluid of less density.

IV. That although the flow of blood m the cavities of
the heart is sufficient to induce, under ordinary conditions,
regular contractions of the organ, still it is necessary that
these movements be further regulated and controlled; and
that this is effected mainly through the agency of the pneu-
mogastric nerves.

V. That the action of the heart may be arrested
through the motor filaments of the pneumogastric nerves
by means of electricity: that this does not take place in
animals poisoned by curara. on account of the paralysis of
the motor nerves. That the motor filaments of the pneu-

* These convulsions have been explained in various ways by physiologists
but never satisfactorily, though they have long been observed.
f See foot-note on page 69.

ACTION OF THE HEART AND RESPIRATION 109

mogastrics are the last which are affected by this agent,
and that in the aUigator they are left almost intact. That
the cause of the arrest of the heart's action by stimulation
of the pneumogastrics is an exaggeration of the force which
regulates the action of the heart, rendering it slower and
more powerful.

VI. That in asphyxia, the cause of the arrest of the
action of the heart is overdistension of its cavities; and
that anything which brings about sufficient distension will
also arrest the action of this organ.

VII. That the auriculo-ventricular valves are closed
by a backward pressure operating during the contraction
of the ventricles, and not by the current of blood from the
auricles to the ventricles.

VIII. That the impression which gives rise to the re-
flex acts of respiration is received from the general system
and not from the lungs or heart. That this impression is
due to the want of oxygen in the tissues and not to stimu-
lating properties of the venous blood. That the exaggera-
tion of this impression constitutes the sense of suffocation
and gives rise, if excessive, to general convulsions.

APPENDIX

Some Points in the Anatomy of the Circulatory
System of the Crocodilus Mississippiensis, or Alli-
gator.— The anatomy of the alligator is imperfectly and in
many respects incorrectly described in most works upon
Natural History. The description of the circulatory appa-
ratus, however, given by Milne Edwards,* in his work on
" Physiology and the Comparative Anatomy of Man and
the Inferior Animals," now in course of publication, is quite
accurate; and as the arrangement of the heart and larger
vessels is peculiar, I have thought that a sketch of these
parts might not be uninteresting.

The heart is quite small in proportion to the size of the
animal, and like the organ in reptiles generally, the ven-
tricular portion is small in proportion to the size of the
auricles. The position, shape, etc., of the auricles do not

* For a full description of the circulatory system of the alligator, see Milne
Edwards, " Le9ons sur la physiologic," etc., tome iii., p. 424 et seq.

no ACTION OF THE HEART AND RESPIRATION

differ from those in other reptiles, except that the right
auricle is much larger than the left; but the ventricular
portion is divided by a complete septum into two chambers,
a right and a left, like the heart of a warm-blooded animal.
From the ventricles arise the two aortie; one from the
left, and one from the right side. There is also a pulmo-
nary artery going to the lungs from the right ventricle.
The right aorta passes immediately over to the left side;
and as it carries venous blood, it may be called the venous
aorta; while the left, or arterial aorta, passes directly over
to the right side. There is no communication betw^een
either auricles or ventricles upon the two sides; but at the
origin of the two aortre is an opening which permits a mix-
ture of venous and arterial l)lood to a limited extent. This
is called the foramen of Pinazza, because its discovery w^as
formerly supposed to belong to him. It was described
by Hentz, an American anatomist, in 1824, in a paper pub-
lished in the " Transactions of the American Philosophical
Society," while Pinazza described it in 1833. Following
out now^ the distribution, etc., of these tw'o aortse, the arte-
rial aorta first gives off a large branch, the brachio-cephalic,
which almost immediately gives off the left subclavian
going to the left superior extremity. The brachio-cephalic
divides into the left subclavian, already mentioned, and a
single carotid artery which goes in the median line to the
base of the skull, there divides into two vessels, which soon
bifurcate and form the external and internal carotids of
the two sides, the internal going to the encephalon, and
the external to the muscles, etc., about the head. Next
is given off the right subclavian artery, distributed to the
right superior extremity. Each subclavian artery, a short
distance from its origin, gives off a small cervical artery,
which goes to the head and is accompanied by the jugular
vein and the pneumogastric nerve. These are the princi-
pal branches which are given off by the arterial aorta alone.
The venous aorta gives off no branches in the neck, but
passes back to the vertebral column, anastomoses by a
branch of considerable size with the arterial aorta, and
sends a branch, larger even than the anastomosing branch,
to some of the abdominal viscera, which are thus supplied
with venous blood. The dorsal aorta is formed by the
union of the arterial aorta with the anastomosing branch

ACTION OF THE HEART AND RESPIRATION in

of the venous aorta, and thus carries mixed blood. It
passes down the back, gives off in its course the inter-
costals, the anterior mesenteric, the renal arteries, the ves-
sels of the posterior limbs, the posterior mesenteric and
finally is distributed to the tail.

The distribution of the blood in this animal is peculiar.
The forelegs, the head and face are supplied with almost
pure arterial blood, as the communication by the foramen
of Pinazza is very imperfect. There is but a single carotid
artery in the neck, and the pneumogastric nerves are found
accompanying the cervical arteries, w'hich are given off
by the subclavians. Some of the abdominal viscera, the
stomach, liver, spleen, etc., are supplied with venous blood.
The kidneys, intestines, hind legs and tail are supplied wdth
a mixture of arterial and venous blood.*

The length of time for which the nervous and muscular
irritability in these animals is retained after death renders
them very valuable in many physiological experiments. I
have found that when poisoned with curara this persisted
for days. For a considerable time, four or five days after
death, even when the weather was quite warm, no decom-
position took place. I do not know that this apparently
antiseptic property of curara has ever been remarked, but
it certainly seemed to retard decomposition in the alligators
upon which I have experimented.

* The description of the heart and arteries, which is here given, is nearly
if not precisely according to the views entertained by Dr. Bennett Dowler, of
New Orleans, who has made extensive researches into the anatomy and physi-
ology of the alligator. These views, however, have never been fully published
by him but were verbally communicated to me.

VI

MECHANISM OF REFLEX NERVOUS ACTION
IN NORMAL RESPIRATION

AN ADDRESS DELIVERED FEBRUARY l6, 1 874, BEFORE THE NEW
YORK SOCIETY OF NEUROLOGY AND ELECTROLOGY *

Published in the " Chicago Journal of Nervous and Mental Diseases " for

April, 1874.

Mr. President, and Gentlemen of the Society:
I shall have the honor this evening of making some re-
marks on the mechanism of nervous reflex action in nor-
mal respiration. A great part of the statements that I shall
make and the views advanced upon this subject are derived
from personal experimentation; but they are not entirely
new, for many of the experiments upon which my views
are based were published in the '' American Journal of
Medical Sciences," in October, 1861. Still, these experi-
ments, which seem to me to be of considerable importance,
have been noticed so Httle in physiological writings that I
venture to assume that they may be new to many of those
who now listen to me.

After Marshall Hall had formularized the ideas of cer-
tain of his predecessors in regard to what he termed re-
flex action, it was pretty generally understood by physi-
ologists that the movements of respiration were of a purely
reflex character, unless they were modified by voluntary
acts; and that the ordinary movements of respiration, which
take place without the intervention of the will, were en-
tirely reflex.

The experiments that I shall detail this evening were
based upon, or rather suggested by an experiment made
in 1664, by the celebrated Robert Hooke, and published
in the " Philosophical Transactions " for 1667. This ex-
periment, though it could not be completely understood

* Phonographically reported by George W. Wells, M. D., of New York.
112

NERVOUS ACTION IN RESPIRATION 113

at the time it was made, in 1664, is very instructive. It
consisted in introducing a bellows into the trachea of a
dog, making an opening into the chest, cutting off a por-
tion of the lungs and forcing air through them; and it was
found that so long as air was forced through the lungs in
this way the animal, though sensible, made no eft'orts at
respiration. I may here anticipate enough to say that I
shall assume that in this experiment, while air was supplied
to the system the animal felt no want of it, had no inclina-
tion to respire and consequently did not respire.

In studying the subject of the reflex nervous action in
respiration, one is immediately struck with the anatomical
relations of the pneumogastric nerves to the respiratory
apparatus; and it is all the more important to study the
relations of these nerves to the process of respiration, as
they arise near that point in the medulla oblongata where
the so-called " vital knot," or the respiratory nerve-cen-
tre, is supposed to be situated.

It may be opportune, perhaps, to rapidly sketch the
■condition of knowledge respecting the influence of the
pneumogastric nerve upon respiration.

The pneumogastric nerve is one of immensely wide
■distribution and is connected with various distinct func-
tions. The branches that are distributed to the respiratory
■organs are the follov/ing:

The superior laryngeals, which are distributed to the
mucous membrane of the larynx and the membrane cover-
ing the top of the larvnx, sending off a branch on either
side to the crico-thyroid muscle, this branch being a mixed
nerve.

Next in order are the inferior, or recurrent laryngeal
nerves, which are distributed to all the intrinsic muscles of
the larynx except the crico-thyroid. These nerves are
composed entirely of motor filaments and are derived from
a variety of sources. The experiments of Bernard, which
have been so often repeated by Dr. Dalton, myself and
others, of extirpating the spinal accessory nerves, or the
•section of the communicating branches to the pneumogas-
trics, show that the spinal accessory is the nerve of phona-
tion; and the filaments that preside over the voice pass
to the larynx through the recurrent laryngeals.

Then, distributed to the lungs themselves, are the an-

114 NERVOUS ACTION IN RESPIRATION

terior and posterior pulmonary branches, which go almost
exclusively to the mucous membrane of the pulmonary
structure. These branches communicate with the sympa-
thetic; but according to Sappey, they do not go to the
walls of the blood-vessels, being distributed to the mem-
brane of the bronchia and the air-vesicles.

So much for the distribution, in general terms, of those
branches of the pneumogastrics which go to the lungs; and
this distribution being so extensive, one can hardly discuss
the reflex nervous action in respiration without taking the
action of these nerves into consideration.

The pneumogastric is originally an exclusively sensory
nerve. Experiments are somewhat ol)scure upon this.
point, on account of the difficulty in irritating the original
roots of the pneumogastrics without involving filaments
of other nerves; still, the careful experiments of Longet
showed that when the spinal cord of animals is opened and
the roots of the pneumogastrics are carefully isolated and
stimulated, no movements follow their irritation. This
shows that the original filaments of the pneumogastric are
not motor; but as the nerve emerges from the cranial cav-
ity, it receives a number of communicating motor fila-
ments, and thus in its course it is a mixed nerve. Follow-
ing out the distribution to the respiratory apparatus, it is
found that the filaments from the superior laryngeal going
to the crico-thyroid muscle are almost exclusively motor;
the motor filaments of the recurrents go to the intrinsic
muscles of the larynx, whereas the true pulmonary branches
are distributed to the mucous membrane. Therefore, ex-
cluding the movements of the larynx, the action of the
pneumogastric in the reflex phenomena of respiration, the-
oretically, would be that of a sensory nerve, conveying to
the respiratory nervous centre an impression, or sensation^
which gives rise to the movements of respiration.

If both pneumogastrics, however, are divided, the re-
spiratory movements are very much diminished in frequen-
cy; and I have in my mind an experiment in which they
were reduced from twenty-four to four or six in a minute;,
yet they still continue; and this simple experiment, so often
performed as a class-demonstration, is a denial of the propo-
sition that the pneumogastrics are the only nerves for the
transmission of the so-called " besoin de respirer," or sense

NERVOUS ACTION IN RESPIRATION 115

of want of air, to the respiratory nerve-centre. If the pneii-
mogastrics were the only nerves having this function, res-
piration should cease after their division; but it does not.

I think that physiologists are not at present able to
explain the cause of the great diminution in frequency of
the respiratory movements after the division of both pneu-
mogastric nerves; but this is, nevertheless, an invariable
phenomenon. In the experiment to which I have referred,
curiously enough the animal did not die; and when I pre-
sented him to my class, about three weeks after the section
of the nerves, the number of respirations had returned to
the normal standard. I imagine that a reunion of the two
ends of the divided nerve had occurred. A post-mortem
examination, the animal being sacrificed in another ex-
periment, showed that the nerves, though not, perhaps,
completely united, had formed a partial union between the
divided extremities.

The condition of the lungs after division of the pneu-
mogastrics — that is, in cases where death follows such
division — is peculiar and was for a long time unexplained
by physiologists. In animals that live for three or four
days and then die, the lungs present pretty generally,
throughout their entire substance, a carnified condition.
They are solid, will sink in water, but still do not present
evidences of inflammation. It was thought at first that
this was due to inflammation; but physiologists failed to
find the positive evidence of any such process. Bernard,
I think, has given the correct explanation of this peculiar
appearance. He observed that when the respiratory move-
ments are gradually diminished in frequency they are im-
mensely increased in depth ; that the in.gpirations are re-
markably prolonged and profound; and that the chest, in
the inspiratory act, is extraordinarily distended. He ad-
vanced the idea that this extreme dilatation of the air-cells
induced capillary haemorrhage in certain parts of the lungs;
that as this extended, the blood coagulated; and finally,
the lungs became almost solid.

Faradization of both pneumogastrics in the neck ar-
rests the respiratory movements, if it is powerful; and this
action is reflex, not direct. If the nen-es are divided, fara-
dization of their peripheral extremities has no effect on
respiration, though it arrests the action of the heart; where-

ii6 NERVOUS ACTION IN RESPIRATION

as faradization of the central ends arrests respiration in the
same way as faradization of the nerves before their division.
FaracHzation of the superior laryngeal nerves arrests respi-
ration and renders the animal motionless. This effect fol-
lows powerful faradization of any of the sensitive nerves,
though not so certainly and promptly as faradization of the
superior laryngeals. If the superior laryngeals are power-
fullv stimulated, respiration stops immediately and is ar-
rested at the instant the current is applied, but more easily
during inspiration than expiration. This arrest of the
respiratory movements is particularly marked as regards
the action of the diaphragm. I have made these prelimi-
nary remarks to show that there is very little known in
regard to the reflex phenomena of respiration operating
through the pneumogastrics.

Although the proposition that I am about to make has
been denied by a few physiologists, still, the greater num-
ber believe that the medulla oblongata is the respiratory
nerve-centre. Adopting this view% which is almost univer-
sally accepted, the mechanism of the reflex phenomena of
respiration may be briefly stated as follows:

These phenomena require three conditions:

I. The physiological integrity of nervous filaments con-
veying a certain impression, or sense, to the nerve-centre.

II. The existence and physiological integrity of the
nerve-centre.

III. Finally, the physiological integrity of the motor
nerves which convey the stimulus that is generated at this
nerve-centre to the inspiratory muscles.

If it be assumed that respiration involves a reflex ac-
tion, it must be admitted that there are nerves which con-
vey certain impressions to the medulla oblongata. The
medulla oblongata is the respiratory centre: and when this
centre is destroyed, the movements of inspiration instantly
and permanently cease. A single series of experiments has
been published by Dr. Brown-Sequard, which are assumed
to prove that respiratory movements may occasionally per-
sist after destruction of the medulla oblongata; but they
have never been confirmed and can not be accepted as
demonstrating that the medulla oblongata is not the cen-
tre for respiration.

The sensation of want of air has been called by the

NERVOUS ACTION IN RESPIRATION 117

French, the " besoin de respirer." It might be well enough
to call it, indeed, the sense of the want of air. Under
ordinary conditions, when respiration is free and when
the surrounding air is pure and in abundance, this sensation
is not felt except at the medulla oblongata. This impres-
sion, however, at proper intervals is conveyed to the me-
dulla and keeps up the respiratory movements, without our
knowledge; and it is only when there is a greater deficiency
of air than usual or when there is an obstruction to respi-
ration, that this sense of want of air becomes a positive
sensation, in the form of a sense of suffocation, more or
less pronounced. I think that the old experiment of Rob-
ert Hooke established this point; and it certainly demon-
strates it, when taken in connection with what has been
learned of late years.

In Robert Hooke's experiment the dog was supplied
artificially with air, completely and efficiently; and it was
noted that so long as the respiratory needs were supplied,
though the animal looked around and was entirely sensible,
he made no respiratory efforts. This showed that during
the free passage of air through the lungs the want of air
was not felt by the medulla oblongata and there was no
stimulus to induce respiratory movements. There was
no necessity felt for respiratory movements and none took
place. This experiment suggested my own observations
made in 186 1. I put an animal, a dog, completely under
the influence of ether, introduced the nozzle of a bellows
into the trachea, opened the chest, turned back the an-
terior walls by breaking the ribs, so that I exposed the
lungs and diaphragm, and then very carefully maintained
artificial respiration. I found that while artificial respira-
tion was complete and efficient the animal remained per-
fectly quiet and made no respiratory efforts. I could see
in this experiment the slightest movement of the dia-
phragm. I then interrupted the artificial respiration for
a moment. Very soon I could see the diaphragm begin
to quiver; it contracted at first slightly; then, more and
more powerfully and rhythmically; and the animal finally
opened the mouth and made ineffectual efforts to breathe.
I then resumed the artificial respiration, and in a short
time, when the respiratory needs were entirely supplied,
the animal became quiet.

ii8 NERVOUS ACTION IN RESPIRATION

I then exposed an artery and introduced in it a stop-
cock, so that I could take blood from the vessel at will.
While I kept up artificial respiration, 1 drew a little blood
from the artery upon a white plate. It had all the charac-
ters of pure arterial blood. 1 then had my assistant, who
was workini^ the bellows, stop the artificial respiration and
I allowed the blood to flow in a small stream from the ar-
tery. I found, always and invariably, that when the blood
began to be dark in the artery, and not before, the animal
made efforts to respire.

There are several views, which have l)een advanced by
physiologists from time to time, as to the location of the
" besoin de respirer."

Marshall Hall and some others thought that it was due
to a want of air in the lungs themselves, and that this
want was conveyed by the pneumogastric nerves to the
medulla oblongata; but I do not see how, under this sup-
position, it is possible to explain respiratory movements
which occur after division of both pneumogastrics.

Reid thought that the sense of want of air w-as due to
the circulation of venous blood in the medulla oblongata.

Berard thought that the sense of want of air, or the
" besoin de respirer," was due to the distension of the left
side of the heart by venous blood when respiration was
arrested. In support of this view, he brought forward the
well-known fact that in certain cases of disease of the heart,
even when the lungs are perfectly normal and completely
filled with air, there is frequently a sense of suffocation.

Vierordt thought that the sense of want of air was
due to the circulation of venous blood in the substance of
the nerves themselves.

Volkmann, in 1842, made the very important observa-
tion that an animal experiences the sense of suffocation
when deprived of air after division of both pneumogastrics.
This fact was well known. Every one who has divided
both pneumogastric nerves in a cat must have noted that
the animal experiences intense distress from suffocation.
In this animal the cartilages of the larynx are very flexi-
ble, and paralysis of both recurrent laryngeal nerves, which
follows division of the pneumogastrics in the neck, causes
the glottis to close in inspiration, so that the animal is
almost immediately deprived of air. Volkmann reasoned

NERVOUS ACTION IN RESPIRATION 119

from this fact, which had often been observed before, that
the sense of want of air resides in the general system and
is not to be referred to any particular organ or organs.

If I may be permitted, now, to continue the account
of my own experiments, I think I can show that it is cer-
tain that the sense of want of air resides in the general sys-
tem; and furthermore, that it is due to a want of oxygen
in the general system.

Here is an animal with the heart and lungs exposed;
a bellows placed in the trachea, and artificial respiration
maintained; but there are no efforts at breathing so long
as air is supplied in sufficient quantity. Put a stop-cock
in the artery, and while artificial respiration is continued,
there is the natural red color to the blood. Stop the respi-
ration, however, and just so soon, and no sooner, as the
blood becomes markedly dark in the arteries, the animal
begins to make efforts at respiration and feels the sense
of want of air. I think this experiment shows that the
sense of want of air is due to the circulation in the system
of blood more or less venous in its character.

\\niat is the cause of this sense of want of air and what
are the conditions of the blood that are different from the
conditions during efficient artificial respiration! Of course,
w^hatever they may be, these two conditions are present:
one, a deficiency of oxygen in the blood that is rendered
more or less venous; and another, the presence in the ar-
teries of blood containing an excess of carbonic acid. The
question now arises, whether the sense of want of air is
due to a deficiency of oxygen in the system or to the irri-
tating qualities of carbonic acid. How can these two con-
ditions be separated experimentally; and how can the
tissues be deprived of oxygen without supplying blood
charged with carbonic acid! A very simple way is to drain
the system of blood; for if blood gets to the system, there
is no question that oxygen will be carried to the tissues,
it being always conveyed l^y the blood, and by the blood
alone. Therefore, if the system is deprived of blood no
oxygen can get to the tissues. Again, if the system is
drained of blood by cutting out the heart, the question
whether or not the sense of want of air is due to the dis-
tension of the left side of the heart by venous blood is
answered. Take this same animal, that is not breathing,

120 NERVOUS ACTION IN RESPIRATION

the respiration being kept up by the bellows, and tie a
ligature around the aorta; he begins to breathe, although
the lungs are supplied with air, for the reason that the oxy-
gen-carrying blood is cut off from the system. If, now, in
this same animal, the heart is suddenly cut out, the sys-
tem is of course almost instantly drained of blood; and the
animal always makes violent and repeated respiratory ef-
forts, although the lungs are fully supplied with air. It
seems to me that these experiments show conclusively
that the sense of want of air is derived from the general
system; that it is due to a w-ant of oxygen in the system,
and not to the irritating properties of carbonic acid; and
that this sense is entirely analogous to the sense of hunger
and the sense of thirst. The sensations of hunger and of
thirst are subjectively referred to the stomach or to the
mouth and fauces; but they really reside in the general
system. If a fistula is made in the stomach of a dog, and
if the animal is allowed to drink, after having been de-
prived of water for a day or two, the water will flow out
through the fistula as fast as it is taken into the stomach;
and although the animal will continue to drink, the water
is not absorbed and the thirst is not satisfied. I have seen
animals drink, in this way, gallons of water, being satisfied
with a moderate quantity after the fistula has been closed.
Also, *if food is taken into the stomach and not absorbed,
the sense of hunger is but momentarily appeased; but
this sense is referred to the stomach because food is nat-
urally introduced into the system by the stomach. So the
sense of want of air. which I believe to be due to the w'ant
of oxygen in the tissues, is referred to the respiratory or-
gans because it is by filling the thorax that this deficiency
in the system is naturally supplied. If the sense of w^ant
of air becomes exaggerated, it constitutes the sense of
suffocation; and this is one of the most distressing of sen-
sations.

It has been observed that convulsions ver\^ often follow
hemorrhage; and this fact has been found difificult of ex-
planation. But hemorrhage is really suffocation; and con-
vulsions are generally observed in suffocation. It makes
very little difference, practically, whether the system is
drained of the oxygen-carrying fluid or whether oxygen
is prevented from going to the lungs; in either case the

NERVOUS ACTION IN RESPIRATION 121

same result follows as far as respiration is concerned; and
in death from profuse or sudden hemorrhage, it seems to
me that the convulsions are in fact no more than convul-
sions due to suffocation. This view seems to offer a satis-
factory explanation of the convulsions following hemor-
rhage. There is one point, however, in this connection,
which is interesting and which I appreciate as fully as any
one who now hears me.

I have assumed that draining the system of blood, by
preventing the oxygen from getting to the system without
carrying to the tissues carbonic acid, proves that the sense
of the want of air is due to a want of oxygen in the tissues
and not to the stimulation of carbonic acid. Carbonic acid
does not originate in the blood, and it is undoubtedly an
excretion. A muscle cut from a living frog and put under
a bell-glass containing oxygen, even though it contains no
blood, will respire. Again, the same muscle in an atmos-
phere of hydrogen will give off a certain quantity of car-
bonic acid. In normal nutrition carbonic acid is carried
away from the tissues, almost as soon as it is formed, by
the blood. If, then, the system is drained of blood, wdiat
is to prevent the carbonic acid from accumulating in the
tissues, and may not this be the cause of the sense of want
of air!

I have tried to imagine experiments to meet this ob-
jection. I have tried to devise some means of getting rid
of the carbonic acid from the tissues, that will not at the
same time either supply oxygen or send through the tis-
sues a fluid like blood, containing carbonic acid. This
flaw in my argument I can not correct experimentally.

One other important point in this connection, which
may be of more interest to some of my hearers than those
to which I have thus far called attention, is the cause of the
first respiratory effort made by the newborn child.

Many of the ancient writers regarded the placenta as
the respiratory organ of the foetus; and it is now known
positively that the foetus in utero gets its oxygen from the
blood of the mother through the placental vessels; but
when the child is born, this source of supply of oxygen is
cut off and the first act of pulmonary respiration is per-
formed, this being the beginning of the function which
continues to the end of life.

122 NERVOUS ACTION IN RESPIRATION

What is the exciting cause of this first respiration! It
has been shown positively, by experiments upon animals,
that the first respiration is clue to an arrest of the placental
circulation. 1 have frequently opened the abdomen of dogs
and cats big with young and taken the young from the
uterus, when they had hardly attained one-fourth of their
size at term, have laid them on a table, and respiratory
movements have always occurred in a very short time after
they were separated from the mother. Experiments have
been made upon animals, by opening the abdomen and
pressing upon the umbilical cord; and in a short time re-
spiratory movements have occurred.

It is well known to gynecologists and obstetricians
that respiratory movements occasionally occur in the hu-
man foetus in utero as a consequence of some interference
with the placental circulation; and the amniotic fluid and
even meconium have been found in the respiratory pas-
sages.

A very thorough exposition of these facts has lately
been made by Dr. B. S. Schultze, in a work published at
Jena, in 1871, entitled " Der Scheintod Neugeborener," in
which the points I have stated are so fully set forth that
there can be no doubt upon the subject. It seems to me
that the respiratory efiforts before birth constitute a very
strong argument in favor of the view that I have stated;
and it seems to me certain that the first respiratory move-
ments after birth are due to the following conditions: The
placental circulation is arrested; the new being feels the
sense of the want of air; and the impression is conveyed
to the medulla oblongata, where a stimulus is generated
which is carried by motor nerves to the inspiratory mus-
cles. The inspiratory muscles then contract, and thus the
lungs are for the first time distended with air.

The general results of the experiments that I have de-
tailed this evening, and which, I may say, I have performed
over and over again, are the following:

Respiration is a reflex phenomenon. The movements
of respiration are reflex. There is a special respiratory
nerve-centre, which is situated in the medulla oblongata.
When this nerve-centre is destroyed, no respiratory move-
ments can take place, because there is no centre to receive
the impression of want of air. Respiratory movements

NERVOUS ACTION IN RESPIRATION 123

are due to an impression made upon the centripetal nerves;
and this impression is due to a want of oxygen in the
general system. The sympathetic system may possibly be
involved in this action, but this point has not been de-
termined. The sense of the want of air, conveyed to the
medulla oblongata, gives rise, under ordinary conditions,
to respiratory movements, which take place without the
consciousness of the individual. Under ordinary condi-
tions respiration is carried on by the medulla oblongata
and does not involve the action of the brain. \\'henever
there is any difficulty in respiration, the sense of want of
air is exaggerated until it becomes a sense of suffocation,
which involves voluntary efforts on the part of the indi-
vidual to supply the want of air.

VII

EXPERIMENTS ON THE EFFECTS UPON RES-
PIRATION OF CUTTING OFF THE SUPPLY
OF BLOOD FROM THE BRAIN AND ME-
DULLA OBLONGATA

Published in the " New York Medical Journal " for November, 1877.

In October, 1861, I published in the " American Jour-
nal of the Medical Sciences " a paper on " Points connected
with the Action of the Heart and with Respiration." In
this paper I contended that the respiratory sense, " besoin
de respirer," of the French, or sense of want of air, which
gives rise to the movements of respiration, is due to a want
of oxygen in the general system. I assumed that in the
medulla oblongata is to be found the centre presiding
over the respiratory movements; that these movements are
reflex; that a certain sense, called the respiratory sense,
is conveyed to the medulla oblongata; and that it is this
sense which is the starting-point of the respiratory acts. I
showed that a dog brought under the influence of ether,
with the heart and lungs exposed and with a bellows in
the trachea, will make no respiratory elTorts so long as air
is efficiently supplied to the lungs by artificial respiration,
an experiment essentially the same as one made by Robert
Hooke, in 1664. In an animal in this condition, I showed
that respiratory efforts were made, when artificial respira-
tion was interrupted, so soon as the blood became dark in
the arteries, having opened an artery and noted the color
of the blood as the experiment progressed.

It seemed to me at that time that the sense of want of
air in this experiment was due to the properties of the dark-
colored blood circulating in the arterial system; and the
question arose in my mind whether this was dependent
upon the deficiency of oxygen in the blood or upon the
presence of carbonic acid. In order to answer this ques-
124

MEDULLA OBLONGATA AND RESPIRATION 125

tion, I drained an animal (a good-sized dog) of blood by
dividing the femoral artery, the chest having been opened
with the animal under the influence of ether and artificial
respiration being maintained in the usual way. In this ex-
periment, although the lungs were fully supplied with air,
violent respiratory efforts were made as the animal became
nearly exsanguine.

In another experiment I divided both pneumogastric
nerves and ascertained that there was no difference in the
phenomena observed, showing that these nerves are not
the sole conductors of the sense of want of air. In still
another experiment I drained an animal of blood by cut-
ting out the heart. This was followed by violent respira-
tory efforts, showing that the sense of want of air has noth-
ing to do with distension of the right cardiac cavities.

From the experiments of which I have thus given a
brief sketch, made in 1861, I concluded that the sense of
want of air, or the respiratory sense, was due to a want
of oxygen in the general system, producing an impression
which was conveyed to the medulla oblongata and which
gave rise to respiratory efforts; that in ordinary respiration,
this reflex action took place unconsciously, but became
exaggerated when there was a great deficiency of oxygen
and was then experienced as a sense of suffocation ; that the
respiratory sense thus had its origin in the general system
and not in the lungs, as the sense of thirst has its seat in
the general system, from deficiency of water, and has sim-
ply a local manifestation in dryness of the throat and fau-
ces. In addition to the experimental arguments in favor
of this view, I saw, in cases of distress in breathing from
deficient circulation, as in certain cases of disease of the
heart in which the lungs are normal, what seemed to me
to be a confirmation of my opinion.

The views which I have just stated were advanced by
me in my work, " Physiology of Man." New York, 1866,
vol. i., page 479, et scq., and in my " Text-Book of Human
Physiology," New York, 1876, page 164, et scq. In Feb-
ruary, 1874, I made an address before the New York So-
ciety of Neurology and Electrology upon the " Mechanism
of Reflex Nervous Action in Normal Respiration," an ab-
stract of which was published in the " New York Medical
Journal," in April of the same year. The full text of this

126 MEDULLA OBLONGATA AND RESPIRATION

address was published in the " Chicago Journal of Nervous
and Mental Diseases," in April, 1874. In this I still ad-
hered to my original view, and I extended my reflections
to the theory of the cause of the first respiration at birth,
respiration in utero by means of the placenta, etc.

At the present day nearly all physiological writers agree
that the sense of want of air is due to want of oxygen and
not to any stimulating or irritating properties of carbonic
acid; and this idea has received confirmation from the ex-
periments of Pfliiger upon the effects of respiration of ni-
trogen, as is seen by the following extract:

" Using bloodletting for ascertaining the condition of the blood
during dyspnoea, I arrived at the following facts : As soon as the
dog begins to breathe pure nitrogen, it is scarcely fifteen seconds
before he makes violent and deep inspirations-; at the end of thirty
seconds, the most intense dyspnoea is observed, the blood is already
almost absolutely black, which must be due to the enormously
rapid tissue-metamorphosis of this animal." *

It is seen that this experiment, made in 1868, is almost
identical in its idea and results with those which I made in
1 861, except that Pfliiger made his animal breathe a gas
not capable of supporting respiration, while I simply de-
prived animals of air. Nearly the same experiment as that
performed by Pfli.iger was made by Rosenthal, in 1862,
who noted that animals suffered no dyspnoea when air or
oxygen was forced through the lungs, but that dyspnoea
was manifested when nitrogen or hydrogen was used in-
stead of oxygen. f

While physiologists are now pretty generally agreed
that the sense of want of air is connected with a deficiency
of oxygen in the blood of the arteries, some writers are of
the opinion that the " sense " is primarily due to a want
of oxygenated blood circulating in the medulla oblongata.
This opinion has been advanced by some authors, but so
far as I know it rests mainly upon theory and has no posi-
tive experimental foundation. Since I made the experi-
ments which form the basis of this article, I have consulted
a number of systematic works upon physiology with refer-

* Pfliiger, " Ueber die Ursache der Athembewegungen, sowie der Dys-
pnoe und Apnoe." — "Archiv fur die gesammte Physiologie," Bonn, 1868, Bd^
i., S. 8q.

t Rosenthal, " Athembewegungen," etc., Berlin, 1862, S. 4.

MEDULLA OBLONGATA AND RESPIRATION 127

ence to the subject under consideration. Most of the
works examined contain no very definite allusions to the
respiratory sense, or at most only brief and unsatisfactory
statements; but in two, I find the following references that
are directly pertinent to the question:

" The first respiratory effort of the foetus is thus produced by
the interruption of the placental respiration, the sudden deficiency
of oxygen and increase of carbonic acid in the blood (Schwartz).
This change in the blood needs to take place locally only in the
vessels of the medulla oblongata, in order to produce this effect;
it occurs, for example, from arrest of the blood in these vessels
(by ligature of the carotid arteries, Kussmaul and Tenner, Rosen-
thal, or by closure of the venous currents from the brain, Hermann
and Escher), by w^hich their blood becomes progressively poorer
in oxygen and richer in carbonic acid " (Hermann, " Grundriss der
Physiologie des Menschen," Berlin, 1870, S. 160).

" If the supply of blood be cut off from the medulla by ligature
of the blood-vessels of the neck, dyspnoea is produced, though the
operation produces no change in the blood generally, but simply
affects the respiratory condition of the medulla itself, by cutting
off its blood-supply, the immediate result of which is an accumu-
lation of carbonic acid and a paucity of available oxygen in the
protoplasm of the nerve-cells in that region" (Foster, "A Text-
Book of Physiology," London, 1877, p. 254).

These quotations from Hermann and from Foster show
clearly that their idea is that the sense of want of air is
due to deficiency of oxygenated blood in the medulla ob-
longata, a view fully sustained by my own experiments.
The observations of Kussmaul and Tenner, referred to by
Hermann, were made with reference to the cause of the
convulsions which so often occur after profuse and sudden
hemorrhage. They are to be found in the elaborate mem-
oir by Kussmaul and Tenner, " On the Nature and Origin
of Epileptiform Convulsions caused by Profuse Bleeding,"
translated and published by the " New Sydenham Soci-
ety," in 1859. Kussmaul and Tenner made a large num-
ber of experiments on rabbits and horses, in which they
observed the effects of tying the great vessels given off
from the arch of the aorta. They noted, after this opera-
tion, great difficulty in respiration and violent convulsions.
They did not, however, abolish the respiratory movements
of the animal by artificial respiration, thus abolishing, for
the time, the respiratory sense, and then note the effects
of ligature of these vessels. The experiments by Rosenthal.

128 MEDULLA OBLONGATA AND RESPIRATION

which are referred to, are probably those contained in his
work on " Die Athembewegungen und ihre Beziehungen
zum NervLis Vagus," Berhn, 1862. In these experiments,
as I have already stated, it is shown that the respiratory
efforts of an animal can be abolished by forcing atmos-
pheric air or oxygen in large quantities through the lungs;
but that the sense of want of air is felt when, in place of
oxygen, nitrogen or hydrogen is employed, by this means
removing the possibility of an irritation from carbonic acid.
These are essentially the same as the observations made
by Pfliiger, in 1868. Rosenthal states very distinctly that
the sense of want of air is due to want of oxygen-carrying
blood in the medulla oblongata; but he does not actually
demonstrate the truth of this proposition by experiments.
The statements by Hermann and by Foster are apparently
based upon the experiments of Kussmaul and Tenner and
of Rosenthal; but I must nevertheless claim that the ex-
periments which I have made upon this subject, which will
be detailed farther on, if they should be confirmed, afford
the first positive proof that the respiratory sense may be
excited by cutting off the arterial supply from the medulla.
There is nothing which I can find in the experiments of
Kussmaul and Tenner or of Rosenthal to actually show
that the sense of want of air is not due to a want of oxy-
gen in the general system.

In reflecting upon this subject during the last few
months, it occurred to me that the question was capable
of a positive solution by experiment. If it is possible to
cut off the arterial supply to the head and medulla oblon-
gata, leaving the rest of the circulation free, an animal
should make respiratory efforts, even though air is supplied
to the lungs, provided that the sense of want of air is due
to a want of oxygenated blood in the medulla. On the
other hand, if the sense of want of air is due to a want of
oxygen in the general system, cutting off the arterial sup-
ply from the head and medulla would have no more effect
than cutting off the supply of oxygen from any other equal-
ly extensive part of the system. In reducing this idea to
the project of an actual experiment, I conceived the follow-
ing: I proposed to tie the vessels of supply to the medulla
oblongata (the vessels given off from the arch of the aorta)
and note the effects; and then to tie the descending aorta

MEDULLA OBLONGATA AND RESPIRATION 129

in the chest and note the effects, leaving the vessels com-
ing from the arch of the aorta free. It seemed to me that
if the respiratory sense is due to want of oxygen in the
general system, tying the aorta in the chest would induce
respiratory efforts as promptly as cutting off the arterial
supply from the medulla. With the view of settling this
question if possible, I made the following experiments,
which so far as they go are definite and satisfactory in
their results. I propose, however, to extend these experi-
ments, and I publish them now simply as preliminary to
further investigations into the subject:

Experiment I., September 30, 1877. — A medium-sized, full-
grown dog was brought completely under the influence of ether.
The trachea was then opened and connected with a bellows and
artificial respiration was maintained. Over the valve of the bel-
lows was placed a sponge, which was saturated with ether from
time to time, so that the animal was kept completely anesthetized
during the experiment. The air in the bellows was also changed
from time to time by pushing up the valve with the fingers and for-
cing out the vitiated air. The chest and abdomen were then laid
open by a continuous incision in the median line, and the ribs were
bent backward and secured with a strong cord tied behind the
"back, so that the lungs and heart were fully exposed. The peri-
cardium was then cut away, the great vessels near the heart were
isolated and loose ligatures were thrown around the trunk of the
innominate artery, the left subclavian artery, the descending vena
cava, the descending portion of the aorta and the ascending vena
cava.* In this way, I was prepared to constrict the several vessels
at will.

When these preliminary steps had been completed, the animal
being entirely vmder the influence of ether and artificial respira-
tion being kept up efficiently, there were absolutely no respiratory
efforts, and the diaphragm, which was exposed, was quiescent.

The artificial respiration was then arrested. In forty-five sec-
onds the animal began to make violent respiratory efforts. Artifi-
cial respiration was then resumed and the respiratory efforts of
the animal ceased. When the artificial respiration was arrested,
I first noticed a movement of the corners of the mouth at regular
intervals and then the mouth was widely opened and the diaphragm
became strongly contracted, also at regular intervals. The time
was taken at the first violent respiratory effort.

The animal being quiet and making no efforts at respiration,
the innominate artery, the left subclavian artery and the descend-

* In the dosf the aorta gives off the innominate artery "which gives off
first the left carotid, and then divides into the right subclavian and right ca-
rotid " (Foster, " Elementary Practical Physiology," London, 1876, p. 13). The
left subclavian artery arises directly from the aorta.

9

I30 MEDULLA OBLONGATA AND RESPIRATION

ing vena cava were tied almost simultaneously, artificial respiration
being constantly and efficiently maintained. In two minutes and
eight seconds the animal began to make respiratory efforts, which
continued so long as the vessels remained constricted.

The ligatures surrounding the vessels mentioned above were
loosened five minutes and twenty-two seconds after they had been
tied, and the respiratory efforts of the animal instantly ceased.
After three minutes, artificial respiration was stopped, and the
animal began to make respiratory efforts in thirty-nine and a half
seconds, which ceased so soon as artificial respiration was re-
sumed.

The descending aorta and the ascending vena cava in the chest
were then tied simultaneously, the vessels arising from the arch
of the aorta being free. This seemed to produce no effect, and no
respiratory efforts were made by the animal for five minutes. The
innominate artery and the left subclavian artery were then con-
stricted, the aorta and ascending vena cava remaining tied. Re-
spiratory efforts by the animal began in one minute and twenty-six
seconds, although artificial respiration was maintained. These ef-
forts ceased when the ligatures around the innominate and sub-
clavian were loosened.

The ligatures were then removed from the descending aorta
and ascending vena cava, and the innominate and left subclavian
arteries were constricted, which was followed by respiratory efforts
after one minute and six seconds. These efforts ceased when the
vessels were freed.

The innominate artery alone was then constricted, but this
seemed to produce no effect, no respiratory efforts being made by
the animal for five minutes. At the end of five minutes the left
subclavian artery was constricted, the constriction of the innomi-
nate artery being maintained. The animal began to make respira-
tory efforts fifty-three seconds after constriction of the subclavian.
These eff'orts ceased on loosening the ligatures.

Artificial respiration was then stopped and the animal began to
make respiratory efforts in ten seconds. The medulla oblongata
was then broken up and the experiment was concluded.

In this experiment I had the aid of my assistant. Dr. C. F.
Roberts, and of Mr. Caspar Griswold, an advanced laboratory
student. As the experiment progressed, it was ascertained that the
vessels could be effectually constricted by making traction on the
ligatures without tying. The constriction could then be instantly
removed. It was also ascertained that constriction of the veins
made no difference in the phenomena observed.

Experiment II., October 2, 1877. — A medium-sized, full-grown
dog was brought completely under the influence of ether. A bel-
lows was fixed in the trachea and the chest and abdomen were
opened as in the preceding experiment. These preliminary steps
were completed at 11.30 a. m. Artificial respiration, which had
been kept up with the bellows, was arrested and the animal made
efforts at respiration in thirty-seven and three-fifth seconds, having
previously been quiet. The innominate artery and the left subcla-

MEDULLA OBLONGATA AND RESPIRATION 131

vian artery were then constricted, the artificial respiration being
continued, and the animal made respiratory efforts in two minutes
and five seconds, having previously been rendered quiet by artificial
respiration. After a few respiratory efforts the ligatures were
loosened and the animal became perfectly quiet, artificial respira-
tion being continued. While the animal was perfectly quiet, artifi-
cial respiration being continued, the descending aorta was tied in
the chest. The aorta was constricted for five minutes and no effect
was observed, artificial respiration being maintained and the animal
remaining perfectly quiet. The heart was then cut out, the system
being thus drained of blood, and the animal made respiratory efforts
in twenty-five seconds.

This experiment was a public demonstration made in a lecture
before the class at the Bellevue Hospital Medical College ; and I
was assisted by Dr. C. F. Roberts, Mr. Caspar Criswold, Dr. C. S.
Conant and Mr. W. L. Wardwell. The experiment was essentially
a repetition of Experiment I., and the results of the two observa-
tions were nearly identical.

The two experiments just detailed show that ligature
of the aorta has no sensible effect upon respiration; but
that ligature of all the vessels given off from the arch of
the aorta, w-hich it would seem must cut off most of the
supply of oxygenated blood from the brain and the medulla
oblongata, produces a sense of want of air, which gives
rise to respiratory efforts, even while artificial respiration
is efficiently maintained. It seems, from the results ob-
served in Experiment I., that it is not enough to tie the
innominate artery, which is equivalent to tying the two
common carotids and the right subclavian artery, but that
it is necessary to tie also the left subclavian artery. This
is explained by the fact that the left subclavian gives off
the vertebral artery, which empties into the basilar artery
and thus carries oxygenated blood to the medulla oblon-
gata.

Taking into account the fact that the respiratory nerve-
centre is situated in the medulla oblongata, the two experi-
ments that I have described, so far as they go, seem to
show conclusively that the sense of want of air is due to
a deficiency of oxygenated blood in the medulla oblongata,
and that this sense is satisfied bv the circulation of such
blood in the respiratory nerve-centre.

Experiment III., October 7, 1877. — A full-grown young dog,
weighing about thirty pounds, was brought completely under the
influence of ether at 10.45 a. m., a bellows was fixed in the trachea,
and the chest and abdomen were opened as in the preceding ex-

132 MEDULLA OBLONGATA AND RESPIRATION

periments. The vessels given off from the arch of the aorta w^ere
then carefully dissected out, and loose ligatures were thrown
around the innominate artery, the two carotids, the right subclavian
artery, the right vertebral artery, the left subclavian artery and the
left vertebral artery. These ligatures were placed around the ves-
sels so that they might be readily found in the course of the experi-
ment, but the vessels were not thereby constricted.

After these preparatory steps had been completed, artificial
respiration was arrested and the animal began to make respiratory
efforts in thirty seconds. Artificial respiration was then resumed
and the animal became quiet.

The two subclavian arteries were then constricted with scrre-
iincs, which, it was ascertained, arrested the blood-current com-
pletely. The animal remained quiet for five minutes, making no
respiratory efforts. The subclavians remaining constricted, both
carotids were then constricted in addition. The animal made re-
spiratory efforts in two minutes and seven seconds after constric-
tion of the carotids. All the vessels were then freed and the ani-
mal became quiet.

Both vertebral arteries and both carotids were then constricted
for five minutes, the animal remaining quiet. These vessels re-
maining constricted, both subclavian arteries were constricted in
addition. The animal made respiratory efforts in one minute and
thirty-five seconds. All the vessels were then freed, and the ani-
mal became quiet.

At 11.40 o'clock the descending aorta in the chest and both
subclavian arteries were tied. This left little more than the carot-
ids to carry blood to the head, and the arterial blood was thus
cut off from the greatest part of the system. The animal remained
quiet for five minutes. The experiment had now lasted fifty-five
minutes and the action of the heart had become considerably weak-
ened. While the aorta and subclavians were still constricted, both
carotids were constricted in addition. The animal remained quiet
for five minutes, but the heart and the great vessels up to the
points of constriction were enormously distended. At the end of
this time the aorta was freed, which relieved the distension. The
animal made respiratory efforts in two minutes and twenty-nine
seconds, but the efforts were not very violent and were not so
rapid as usual. All the vessels were freed and the animal became
quiet.

Artificial respiration was then arrested and the animal made
respiratory efforts in twelve seconds. Artificial respiration was
resumed and the animal became quiet.

The innominate artery and the left subclavian artery were then
constricted and the animal made respiratory efforts in one minute
and fifteen seconds, but the action of the heart had become very
feeble.

The experiment had lasted one hour and fifteen minutes and
was concluded with the last observation.

In this experiment I was assisted by Dr. C. F. Roberts, Mr.
Caspar Griswold and Dr. G. S. Conant.

MEDULLA OBLONGATA AND RESPIRATION 133

This experiment substantially confirmed the results ob-
tained in Experiments L and IL When the aorta, both
subclavian arteries and both carotids were constricted, the
pressure of blood in these vessels was enormous, and some
blood may have found its w-ay to the brain and medulla
oblongata. The distension of the vessels was so great that
this part of the experiment was not very satisfactory. Re-
spiratory efforts were made by the animal, however, when
the distension was relieved by freeing the aorta, the subcla-
vians and the carotids remaining constricted.

In all the experiments the animals were kept complete-
ly under the influence of ether, and artificial respiration
was kept up efficiently unless otherwise stated.

Deductions and Conclusions. — When I made my
first experiments on the seat of the sense of want of air
which gives rise to respiratory movements, in 1861, I
attached to them considerable importance; and I thought
that I had proved experimentally that the sense of want
of air is due to a deficiency in oxygen in the system at
large. The main features of the experiments which I made
at that time I have already stated. My object in making
these new experiments was to study the effects of cut-
ting off the supply of oxygenated blood from different
parts.

I think it may be assumed, as I have already stated,
that the sole respiratory nerve-centre is in the medulla
oblongata; and I endeavored to devise some means of cut-
ting off the arterial supply of blood from this part. Ani-
mals respire when all of the encephalic centres have been
destroyed except the medulla oblongata, so that it is im-
probable that cutting off the supply of blood from the brain
would affect the muscles of respiration, provided artificial
respiration is ei^ciently maintained. Blood can get to the
medulla oblongata from the internal carotids, which are
connected with the circle of Willis, from the vertebral ar-
teries, which unite to form the basilar artery,* and perhaps
from other vessels; but it is certain that if all the arteries
given off from the arch of the aorta are tied the medulla
must be deprived of oxygenated blood.

In Experiment I. the innominate artery and the left

* The basilar artery is much longer in the dog than in the human subject.

134 MEDULLA OBLONGATA AND RESPIRATION

sul)clavian artery were constricted * and the animal made
respiratory efforts in two minutes and eight seconds, not-
withstanding that artificial respiration was kept up.

In Experiment II. the same vessels were constricted
and the animal made respiratory efforts in two minutes
and five seconds.

In Experiment III. both suljclavian arteries and both
carotids were constricted and the animal made respiratory
efforts in two minutes and seven seconds. Both vertebral
arteries and both carotids were constricted and the animal
made no respiratory efforts for five minutes; but respira-
tory efforts were made in one minute and thirty-five
seconds after both subclavians had been constricted in
addition to the vertebrals and carotids.

It seems from all of these experiments that in order
to induce respiratory efforts in an animal under the in-
fluence of ether and with the lungs supplied with air by
artificial respiration, either the innominate artery and the
left subclavian artery or both subclavians, both carotids
and both vertebral arteries must be tied. In other words,
according to my view of the cause of these respiratory
efforts, the supply of blood to the medulla oblongata can
not be cut off completely except by tying all the vessels
given off from the arch of the aorta.

As the result of the experiments which I have just
detailed, I must now modify the view which I advanced
in 1861 as a conclusion from experiments then published,
which I have maintained up to the present time, that the
sense of want of air, which is the starting-point of the move-
ments of respiration, is due to want of oxygen in the
general system. My experiments made in 1861 were accu-
rate and the conclusions from them seemed to be legiti-
mate; but these experiments were incomplete. The ex-
periments which I have just reported, taken in connection
Avith my experiments of 1861, lead me to conclude that the
sense of want of air is due to a want of circulation of oxy-
genated blood in the medulla oblongata.

I trust that my experiments, which are by no means
difficult or uncertain in their results, may be repeated and

* In the first experiment the great veins were also tied, but this seemed to
make no difference in the phenomena following con^^triction of the arteries, and
the veins were left free in the other experiments.

MEDULLA OBLONGATA AND RESPIRATION 135

either verified or corrected by other physiologists. The
idea that the sense of want of air is due to a deficiency of
oxygen in the medulla has been adopted by some writers;
but so far as I know, my experiments are the first to show,
by actual demonstration, that this view is correct.

In another paper I propose to treat of the respiratory
sense much more fully and to review the literature of the
subject. Many interesting and important points will un-
doubtedly be involved in a full discussion of the nervous
mechanism of the respiratory movements; and among them
will be the question as to whether the normal respiratory
movements are actually reflex in their character, as has
been generally supposed, or whether they are due to a
■direct excitation of the nerve-cells in the respiratory centre.

VIII

IS THE ACTION OF THE MEDULLA OBLONGA-
TA IN NORMAL RESPIRATION REFLEX?

Published in the " American Journal of the Medical Sciences" for July, 1880.

In connection with a series of experiments published
in 1877, the question occurred to me whether or not the
action of the medulla oblongata in normal respiration could
strictly be classed among those operations recognized by
physiologists as reflex. That the medulla oblongata con-
tains the centre presiding over certain reflex phenomena^
acting through some special nerves, there can be no doubt.
The centres in the medulla seem to serve as coordinators
of the muscles of expression, and have certain reflex func-
tions connected with the respiratory muscles, such as
coughing, sneezing, etc. In certain instances, also, in
which respiration is temporarily suspended, a stimulation
of parts of the general surface, as by a dash of cold water,
will excite respiratory movements. Such an action as the
one last mentioned might properly be called reflex; but
the phenomena which I here propose to consider are those
of ordinary, normal respiration and the exaggerations of
the respiratory sense which amount to a more or less in-
tense feeling of want of air.

The general view under which physiologists have been
accustomed to regard the respiratory movements as reflex
is the following: It has been thought that there existed in
some part of the organism or in the system at large a
certain sense, which may be called the sense of want of
air, the respiratory sense, or the " besoin de respirer," of
the French, dependent upon either an actual or an im-
pending deficiency of oxygen or upon an impression pro-
duced by the circulation of blood containing carbonic acid
in parts that should normally receive oxygenated blood.
This " respiratory sense " has been taken as the starting-
136

MEDULLA IN NORMAL RESPIRATION 137

point of the respiratory acts. Regarding a reflex phe-
nomenon as involving an impression conveyed by afferent
nerves to a nerve-centre, which impression, by the action
of the nerve-centre, is converted into a stimulus and is
reflected along certain efterent nerves to muscles, the con-
ditions of the operation of reflex action in ordinary respi-
ration have been regarded as complete. The respiratory
sense, according to this view, is conveyed by certain cen-
tripetal nerves to the medulla oblongata, and here it is con-
verted into a stimulus which is conveyed by the proper
centrifugal nerves to the respiratory muscles, and there
follows an act of inspiration.

My principal object, in this article, is to discuss the
question of the so-called reflex action of the medulla ob-
longata in respiration, drawing conclusions mainly from
my own experiments. I shall not, therefore, attempt to
give a full account of the literature bearing upon the action
of the medulla oblongata as the respiratory nerve-centre
or even of the experiments which relate to its reflex func-
tion, except in so far as the latter have been followed by
important advances or changes in the views of physiolo-
gists or as their history involves questions of priority.

In 1809 Legallois made a number of experiments upon
rabbits in which he showed that respiration ceased sudden-
ly when a section of the medulla oblongata was made to
include the origin of the eighth pair of nerves; but that
the respiratory acts continued when the cerebrum, cere-
bellum and a part of the medulla oblongata were removed
by successive slices from before backward.* Flourens ex-
tended the observations of Legallois and fixed the limits
of the respiratory nerve-centre in the rabbit, between the
upper border of the origin of the pneumogastrics and a
line drawn about a quarter of an inch below the lowest
point of origin of these nerves. f Longet and Flourens,
in later observations, restricted the limit still further, and
showed that it was confined to the gray matter of the lat-
eral tracts, or the intermediary fasciculi.:}: Since the publi-

* Legallois, " Experiences sur le principe de la vie." Qiuvres, Paris, 1824,
tome i., p. 64. The date of these experiments is given by Legallois on page
71 of the above-mentioned work.

f Flourens, " Systeme nerveux," Paris, 1842, p. 204.

X Longet, " Traite de physiologic," Paris, 1869, tome iii., pp. 387, 388.

138 MEDULLA IN NORMAL RESPIRATION

cation of the experiments of Flourens, nearly all physiolo-
gists have agreed that the respiratory nerve-centre is situ-
ated in some part of the gray matter of the medulla, and
this view I accept without reserve. Its most notable op-
ponent, however, is Dr. Brown-Sequard. This author con-
tends that the arrest of respiratory movements which fol-
lows destruction of the medulla is due to irritation of
surrounding parts and not to the destruction of the so-
• called respiratory centre; and that in certain cases, the
movements may become reestal)lishe(l after the irritation
has subsided.* In the absence of their full confirmation
by other observers, I do not regard the experiments or the
conclusions of Dr. Brown-Sequard as satisfactory; and I
still hold that the medulla oblongata is the centre presiding
over the respiratory acts.

Marshall Hall, in his memoir on the " Reflex Function
of the Medulla Oblongata and Medulla Spinalis," published
in 1833, says nothing in regard to the reflex character of
respiration. In the Croonian Lectures, delivered before
the Royal College of Physicians in 1850, he advances the
view that the normal respiratory acts are reflex and de-
pendent upon excitation of the pneumogastric nerves by
the accumulation of carbonic acid evolved in the lungs
from the venous blood. f Subsequent observations, how-
ever, have shown that the theory proposed by Marshall
Hall is incorrect; and at the present day it is not adopted by
any ph^ysiologist of recognized authority. As early as 1839,
John Reid suggested that the sense of want of air was due
in a measure to the circulation of venous blood in the
medulla oblongata.:]: This fact is interesting in view of the
results of recent experiments which will be detailed farther
on. In 1 84 1 Volkmann made a number of experiments,
the conclusion drawn from which was that the sense of
want of air depends upon a certain condition of the general

* Brown-S^quard, " Recherches sur les causes de mort apres I'ablation de la
partie de la moelle allongee qui a ete nominee point vital." Journal de la
physiologic, Paris, 1858, tome i., p. 217 et seq. ; and " Recherches experimen-
tale sur la physiologie de la moelle allongee. Ibid., i860, tome iii., p. 151 et seq.

f Marshall Hall, " Synopsis of the Diastaltic Nervous System," London (no
■date), p. 43.

\ Reid, "An Experimental Investigation into the Functions of the Eighth
Pair of Nerves," etc.. Part Second. " Anatomical and Physiological Re-
searches," Edinburgh, 1848, p. 285; and "Edinburgh Medical and Surgical
Journal," April, 1839.

MEDULLA IN NORMAL RESPIRATION 139

system as well as an impression made upon the pulmonary
mucous membrane.

" The respiratory movements appear really to be of a reflex
character in the following way : The exciting agent is carbonic
acid — not that which has become free in the air passages, but that
which is contained in the blood ; the situation of the stimulation
is in every part of the body, not alone the pulmonary mucous mem-
brane ; finally, the nerves brought into action are all nerves which
conduct centripetally operating toward the medulla oblongata, not
exclusively the vagus.'' *

Volkmann states, immediately following the passage
just quoted, that the respiratory movements find their im-
pulse in a " respiratory necessity "; and that this originates
in the eiitire system; that all animals require oxygen from
the blood in place of the carbonic acid which they give
up to the blood; and that so soon as the blood is over-
charged with carbonic acid, this " necessity " (respiratory)
can not be satisfied.

In 1 861 I made a series of experiments with the view
of ascertaining the situation of the respiratory sense, adopt-
ing the view, which was then almost universally received,
that the respiratory acts are reflex. f The main points in
these experiments were the following:

When the chest was opened in a living dog and a bel-
lows fixed in the trachea, so long as artificial respiration
was efficiently performed the animal made no respiratory
efforts. In these experiments the animals usually were
etherized; but in several instances they were allowed to
come from under the influence of the anesthetic. The dia-
phragm and other important respiratory muscles were de-
nuded and fully exposed to view. This was almost an
exact repetition of an experiment performed by Robert
Hooke in 1664.

An artery was then opened and the blood was allowed
to flow in a small stream. When the artificial respiration
was suspended the animal began to make respiratory ef-
forts so soon as the blood became dark in the arteries; but

* Volkmann, " Ueber die Bewegungen des Athems und Schluckens," etc.
" Archiv fiir Anatomie, Physiologie, und wissenschaftliche Medicin," Berlin,
1841, S. 342.

t Flint, " Experimental Researches on Points connected with the Action
of the Heart and vnth Respiration." — " American Journal of the Medical Sci-
ences," October, 1861, p. 372 et seq.

I40 MEDULLA IN NORMAL RESPIRATION

when artificial respiration was resumed, so soon as the
blood became again bright red in the arteries the respira-
tory efforts ceased.

In order to ascertain whether the sense of want of air
was (hie to a deficiency of oxygen or to the presence of
carbonic acid in the blood of the arteries, I drained the
animals of blood, sometimes from a large artery and some-
times by excising the heart, at the same time keeping up
artificial respiration carefully and efficiently. As the sys-
tem became drained of blood, there always occurred vigor-
ous and even violent respiratory efforts, although the lungs
were kept supplied with pure air.

From these experiments I reasoned that the respira-
tory movements being, as I thought, reflex, the sense of
want of air depended upon a deficiency of oxygen in the
system at large and not upon the presence of carbonic
acid in the blood of the arteries; for the sense seemed to
be felt by the animals in my experiments, when the system
was drained of blood, the arteries containing no blood
charged with carbonic acid.

In 1868, about seven years after the publication of my
experiments in the " American Journal of the Medical Sci-
ences," Pfliiger published a very interesting article upon
the same question.* In this article a very elaborate review
is given of the literature of the subject. He first refers to
the opinions of various authors in regard to the question
of a difference in color between the blood of the um-
bilical arteries and the umbilical vein, and then goes on to
state that " it is established without doubt that, after birth,
there is a diminution in the quantity of oxygen in the body
of the newly born, which, as the following researches will
show, is the real cause of respiration." The experiments
which led Pfliiger to the conclusion that the sense of want
of air, dyspnoea, and apnoea were due to a want of oxygen
in the system consisted mainly in causing animals to
breathe an irrespirable gas, such as pure nitrogen. f

* Pfliiger, " Ueber die Ursache der Athembewegune:en, sowie der Dvspnoe
und Apnoe." — " Archiv fur die gesammte Physiologic," Bonn, 1S68, Bd. i., S.
bl et seq.

\ Rosenthal, in his work on the "Respiratory Movements," published in
1862, anticipated the experiments of Pfliiger upon the influence of the insuffla-
tion of irrespirable gases upon the respiratory movements. He noted that the
manifestations of dyspnoea ceased in animals when the chest had been opened

MEDULLA IN NORMAL RESPIRATION 141

" Using blood-letting for ascertaining the condition of the blood
during dyspnoea, I arrived at the following facts : As soon as the
dog begins to breathe pure nitrogen, it is scarcely fifteen seconds
before he makes violent and deep inspirations ; at the end of thirty
seconds, the most intense dyspnoea is observed, the blood is already
almost absolutely black, which must be due to the enormously
rapid tissue-metamorphosis of the animal. At the end of one min-
ute the animal is already almost asphyxiated. The respiratory
movements are very infrequent or have ceased, but the heart still
beats." *

Then follows a series of examinations of the blood un-
der normal conditions at various times after causing an
animal to breathe pure nitrogen. In one of these observa-
tions, after causing a dog to breathe nitrogen for one min-
ute, the oxygen of the blood was found to be reduced from
14.35 P^^ cent, to 0.2 per cent., and the carbonic acid from
36.9 per cent, to 29.9 per cent., showing a very great
diminution in oxygen and a considerable diminution in car-
bonic acid. " No one, therefore, can be of the opinion
that dyspnoea and asphyxia in breathing indifferent gases
is connected with the accumulation of carbonic acid." f

While Pfliiger assumed to give a review of the literature
of the subject under investigation, he made no mention
of my experiments published in 1861, although the results
were nearly identical with his own. Later observations
and experiments, however, have convinced me that the
interpretations of my earlier experiments, as well as those
made by Pfliiger, were incorrect. I do not now believe
that the acts of respiration are purely reflex in the sense
in which this term is generally used; and I do not believe
that the sense of want of air is due to a deficiency of oxy-
gen in the system at large. I have become convinced, by
experiments made in 1877, that the real cause of the sense
of want of air, with its various exaggerations and modifi-
cations, is a deficiency in or an absence of oxygenated

and oxygen was passed through the lungs, but that they continued when, instead
of oxygen, nitrogen or hydrogen was used, " although in this case the carbonic
acid, as well as the oxygen, was removed from the blood." From this it appears
to follow that it is not the increased quantity of carbonic acid, but the dimin-
ished quantity of oxygen which, in dyspnoea, produces the mediate or the im-
mediate stimulation of the respiratory central organ. (Rosenthal, " Die Athem-
bewegungen," etc., Berlin, 1862, S. 4.) My own experiments were published
in i86t.

* Pfluger, op. cit., S. 89.

t Ibid., S. 95.

142 MEDULLA IN NORMAL RESPIRATION

blood in the vessels of the medulla oblongata. This opinion
has been entertained by certain physiologists on theoretical
grounds; but so far as I know, it had not been sustained
by direct experiment prior to my observations in 1877.

In 1877 I made a series of experiments which seemed
to me to demonstrate conclusively that the sense of want
of air is due to a deficiency of oxygen-carrying blood in
the medulla oblongata. The details of these experiments
have already been published,* and I shall here give merely
a summary of the results.

If the chest of a dog is opened, the animal being under
the influence of ether, and if artificial respiration is effi-
ciently maintained the animal will make no respiratory
efforts so long as fresh air in sufficient quantity is supplied
to the lungs. This is an old experiment, dating from the
time of Robert Hooke, in 1664, and has been repeatedly
verified.

Air still being supplied in adequate quantity to the
lungs, if the aorta is tied or the system drained of blood, the
animal will make violent respiratory efforts under the in-
fluence of the sense of want of air. This is due to the fact
that the oxygen can not get to the system or to some part
or parts of the system; and this demonstration w^as made
and published by me as early as 1861. Similar results were
obtained by Rosenthal in 1862 and by Pfliiger in 1868.

In 1877 it occurred to me that it was possible to ascer-
tain by experiment whether the sense of want of air was
due to a want of oxygen in the general system or in some
restricted part. It being so w^ell established that the me-
dulla oblongata is the respiratory nerve-centre, I was nat-
urally led to look for some means of cutting off the supply
of blood from this part. This can easily be done by tying
the innominate artery and the left subclavian artery in a
dog, in this animal the aorta giving off from the arch these
two vessels which are the only sources of supply of blood
to the head and the anterior extremities. The following
experiment, which I copy from my article published in
1877, shows the effect of constricting the vessels given
off from the arch of the aorta. This experiment is a type

* Flint, " Experiments on the Effects upon Respiration of cutting off the
Supply of Blood from the Brain and the Medulla Oblongata." — " New York
Medical Journal," November, 1877, vol, xxvi., p. 449.

MEDULLA IN NORMAL RESPIRATION 143

of many others made in my laboratory and in public dem-
onstrations.

September 30, 1877. — A medium-sized, full-grown dog was
brought completely under the influence of ether. The trachea was
then opened and connected with a bellows and artificial respiration
was maintained. Over the valve of the bellows was placed a
sponge, which was saturated with ether from time to time, so that
the animal was kept completely anesthetized during the experi-
ment. The air in the bellows was also changed from time to time
by pushing up the valve with the fingers and forcing out the vitiated
air. The chest and abdomen were then laid open by a continuous
incision in the median line, and the ribs were bent backward and
secured with a strong cord tied behind the back, so that the lungs
and heart were fully exposed. The pericardium was then cut
away, the great vessels near the heart were isolated and loose liga-
tures were thrown around the trunk of the innominate artery, the
left subclavian artery, the descending vena cava, the descending
portion of the aorta, and the ascending vena cava.* In this way,
I was prepared to constrict the several vessels at will.

When these preliminary steps had been completed, the animal
being entirely under the influence of ether and artificial respiration
being kept up efificiently, there were absolutely no respiratory ef-
forts, and the diaphragm, which was exposed, was quiescent.

The artificial respiration was then arrested. In forty-five sec-
onds the animal began to make violent respiratory efTorts. Artifi-
cial respiration was then resumed, and the respiratory efTorts of
the animal ceased. When the artificial respiration was arrested, I
first noticed a movement of the corners of the mouth at regular
intervals and then the mouth was widely opened and the diaphragm
became strongly contracted, also at regular intervals. The time
was taken at the first violent respiratory effort.

The animal being quiet and making no efforts at respiration,
the innominate artery, the left subclavian artery and the descend-
ing vena cava were tied almost simultaneously, artificial respira-
tion being constantlv and efficiently maintained. In two minutes
and eight seconds the animal began to make respiratory efforts,
which continued so long as the vessels remained constricted.

The ligatures surrounding the vessels mentioned above were
loosened five minutes and twenty-two seconds after they had been
tied, and the respiratory efforts of the animal instantly ceased.
After three minutes, artificial respiration was stopped, and the ani-
mal began to make respiratory efforts in thirty-nine and a half
seconds, Avhich ceased so soon as artificial respiration was re-
sumed.

The descending aorta and the ascendinsf vena cava in the chest

* In the dog, the aorta gives ofif the innominate artery, " which gives off
first the left carotid, and then divides into the right subclavian and right ca-
rotid " (Foster, " Elementary Practical Physiology," London, 1876, p. 13). The
left subclavian artery arises directly from the aorta.

144 MEDULLA IN NORMAL RESPIRATION

were then tied simultaneously, the vessels arising from the arch
of the aorta being free. This seemed to produce no effect, and
no respiratory efforts were made by the animal for five minutes.
The innominate artery and the left subclavian artery were then
constricted, the aorta and ascending vena cava remaining tied.
Respiratory eft'orts by the animal began in one minute and twenty-
six seconds, although artificial respiration was maintained. These
efforts ceased when the ligatures around the innominate and sub-
clavian were loosened.

The ligatures were then removed from the descending aorta
and ascending vena cava, and the innominate and left subclavian
arteries were constricted, which was followed by respiratory efforts
after one minute and six seconds. These efforts ceased when the
vessels were freed.

The innominate artery alone was then constricted, but this
seemed to produce no effect, no respiratory efforts being made by
the animal for five minutes. At the end of five minutes the left
subclavian artery was constricted, the constriction of the innomi-
nate artery being maintained. The animal began to make respira-
tory efforts fifty-three seconds after constriction of the subclavian.
These efforts ceased on loosening the ligatures.

Artificial respiration was then stopped and the animal began
to make respiratory efforts in ten seconds. The medulla oblongata
was then broken up and the experiment was concluded.

In this experiment I had the aid of my assistant, Dr. C. F.
Roberts, and Mr. Caspar Griswold, an advanced laboratory stu-
dent. As the experiment progressed, it was ascertained that the
vessels could be effectually constricted by making traction on the
ligatures without tying. The constriction could then be instantly
removed. It was also ascertained that constriction of the veins
made no difference in the phenomena observed.

The general result of all my experiments made on the
plan of the one just detailed was that invariably, when the
innominate and the left subclavian artery were tied, the
dogs began to make respiratory efforts in a little more
than two minutes after the ligation, but the animals re-
mained quiet after ligation of the aorta in the chest. The
respiratory efforts continued so long as the vessels going
off from the arch of the aorta remained constricted, and
they ceased almost immediately when the Hgatures were
loosened. During all of my observations upon the effects
of tying the various bloodvessels, artificial respiration was
kept up constantly and efficiently. Under the view which
I was led to adopt by the results of these experiments —
that the sense of want of air was due to a deficiency of
oxygen-carrying blood in the medulla oblongata — I could
not be certain that the arterial blood was entirely shut off

MEDULLA IN NORMAL RESPIRATION 145

from the medulla without tying the innominate and the
left subclavian. It seemed to make no ditTerence in the
results of the experiments whether the great veins were
tied or left free. In all of the experiments the excitability
of the medulla was repeatedly shown by arresting artificial
respiration from time to time. The animals began to make
respiratory efforts in thirty to forty-five seconds after the
arrest of artificial respiration.

The results of my experiments show that when the
flow of oxygenated blood is cut off from the parts supplied
by the vessels given off from the arch of the aorta in a
living animal, the sense of the want of air is excited, as is
evident from repeated and often violent respiratory efforts,
although air is supplied to the lungs. Respiration will
continue when all of the encephalic ganglia, with the ex-
ception of the medulla oblongata, have been removed;
and it is well known that this, the medulla, is the sole
respiratory nervous centre. One would naturally look,
then, to influences operating upon the medulla oblongata
for an explanation of these respiratory efforts. It does not
seem that these movements can be clue to an impression
received by the medulla from the general system and due
to want of oxygen; for when the descending aorta is tied
in the chest no respiratory efforts are made. The move-
ments, indeed, occur only when the medulla oblongata is
deprived of blood; and the vessels which it is necessary to
tie in order to produce this result involve a smaller part
of the general systemic circulation than when the descend-
ing aorta is tied in the chest.

I do not assume that the view just enunciated is entirely
novel; but so far as I know, the observations made in 1877
were the first to sustain such a view by positive experi-
mental evidence. Upon this point I have nothing to add
to what I have already stated in connection with the fol-
lowing quotations: *

" The first respiratory effort of the foetus is thus produced by
the interruption of the placental respiration, the sudden deficiency
of oxygen and increase of carbonic acid in the blood (Schwartz).
This change in the blood needs to take place locally only in the
vessels of the medulla oblongata, in order to produce this effect;
it occurs, for example, from arrest of the blood in these vessels

* "New York Medical Journal," November, 1877, vol. xxvi., p. 452.
10

146 MEDULLA IN NORMAL RESPIRATION

(by ligature of the carotid arteries, Kussmaul and Tenner, Rosen-
thal, or by closure of the venous currents from the brain, Hermann
and Escher), by which their blood becomes progressively poorer in
oxygen and richer in carbonic acid" (Hermann, " Grundriss der
Physiologic des Menschen," Berlin, 1870, S. 160).

"If the supply of blood be cut off from the medulla by ligature
of the blood-vessels of the neck, dyBi)noea is produced, though the
operation produces no change in the blood generally, but simply
affects the respiratory condition of the medulla itself, by cutting
off its blood supply, the immediate result of which is an accumula-
tion of carbonic acid and a paucity of available oxygen in the pro-
toplasm of the nerve-cells in that region."' (Foster, " A Text-Book
of Physiology," New York, 1880, p. 2,77-)

These quotations from Hermann and from Foster show clearly
that their idea is that the sense of want of air is due to deficiency
of oxygenated blood in the medulla oblongata, a view fully sus-
tained by my own experiments. The observations of Kussmaul
and Tenner, referred to by Hermann, were made with reference
to the cause of the convulsions which so often occur after profuse
and sudden hemorrhage. They are to be found in the elaborate
memoir by Kussmaul and Tenner, " On the Nature and Origin of
Epileptiform Convulsions caused by Profuse Bleeding," translated
and published by the " New Sydenham Society," in 1859. Kuss-
maul and Tenner made a large number of experiments on rabbits
and horses, in which they observed the effects of tying the great
vessels given off from the arch of the aorta. They noted, after
this operation, great difficulty in respiration and violent convul-
sions. They did not, however, arrest the respiratory movements
of the animal by artificial respiration, thus abolishing, for the time,
the respiratory sense, and then note the effects of ligature of these
vessels. The experiments by Rosenthal, w^hich are referred to, are
probably those contained in his work " Die Athembewegungen und
ihre Beziehungen zum Nervus Vagus," Berlin, 1862. In these
experiments, as I have already stated, it is shown that the respira-
tory efforts of an animal can be abolished by forcing atmospheric
air or oxygen in large quantities through the lungs, but that the
sense of want of air is felt when, in place of oxygen, nitrogen
or hydrogen is employed, by this means removing the possibility of
an irritation from carbonic acid. These are essentially the same
as the observations made by Pfliiger, in 1868. Rosenthal states
very distinctly that the sense of want of air is due to want of
oxygen-carrying blood in the medulla oblongata ; but he does not
actually demonstrate the truth of this proposition by experiments.
The statements by Hermann and Foster are apparently based upon
the experiments of Kussmaul and Tenner and of Rosenthal ; but
I must nevertheless claim that the experiments which I have made
upon this subject, which \v\\\ be detailed farther on, if they should
be confirmed, afford the first positive proof that the respiratory
sense may be excited by cutting off the arterial supply from the
medulla. There is nothing which I can find, in the experiments
of Kussmaul and Tenner or of Rosenthal, which actually shows

MEDULLA IN NORMAL RESPIRATION 147

that the sense of want of air is not due to a want of oxygen in the
general system.

All the experiments that I have thus far referred to
have of necessity involved placing the animals on which
the observations were made under conditions exceedingly
unnatural. It can not be assumed that after the chest has
been opened the nerve-centres possess a degree of sensi-
bility and a power of action entirely normal. Still it is
not easy to see how such a modification of the natural con-
ditions can be avoided; and we must reason as best we
can from the observations that have been made, keeping
in view the experimental conditions.

It is certain that oxygen may be artificially supplied
to the lungs in a living animal so efficiently as to abolish
for the time the sense of want of fresh air, to satisfy the
requirements of the system for oxygen and to cause all
respiratory efforts on the part of the animal to cease.
When artificial respiration is arrested and the blood be-
comes dark in the arteries, when the blood is drained from
the system, artificial respiration being continued, or when
oxygenated blood is shut off from the medulla oblongata,
the animal makes respiratory efforts.

Taking into consideration all the experiments bearing
upon this point, they seem to show beyond question that,
under the conditions indicated above, the sense of want of
air. the stimulus or whatever it may be that causes the
animal to make respiratory efforts depends tipon some
peculiar condition in the medulla oblongata. Still, under
the conditions mentioned; that is, an animal under the
influence of ether with the chest opened and a bellows in
the trachea, when artificial respiration is interrupted, the
respiratory efforts begin in thirty to forty-five seconds.
There is then blood in the medulla oblongata, contain-
ing less oxygen and more carbonic acid than normal
arterial blood and passing through the capillaries under
great pressure, slowly and with difficulty. When, on the
other hand, all the vessels given off from the arch of the
aorta are tied, respiratory efforts begin in a few seconds
more than two minutes. While this latter experiment,
taken by itself, shows that shutting off the oxygen-carrying
fluid from the medulla oblongata excites the sense of want
of air, the question at once arises: why, when the vessels

148 MEDULLA IN NORMAL RESPIRATION

which supply the medulla oblongata are filled with blood
of a venous character, is the respiratory sense excited so
much more promptly than when the arteries are tied? In
other words, if it is assumed that shutting off the blood
from the medulla oblongata will excite the respiratory
sense by cutting off the supply of oxygen, and that this
will induce respiratory efforts in about two minutes, why
does the simple interruption of artificial respiration, which
causes blood of a venous character to go to the medulla
oblongata, induce respiratory efforts in about thirty sec-
onds?

This is a question which I have in vain attempted to
solve to my entire satisfaction. When artificial respiration
is arrested and the circulation is not interfered with by
the tying of vessels, the venous blood passes through the
lungs and back to the left side of the heart without losing
its carbonic acid and without receiving a fresh supply of
oxygen. Under these conditions, it passes through the
great vessels given off from the arch of the aorta to the
medulla oblongata as well as to other parts; and the main
obstruction to the blood-current, which produces such in-
tense engorgement of the cardiac cavities, exists in the
systemic capillaries. It is fair to infer that the capillaries
of the medulla are engorged as well as others. This being
the condition, it is logical to assume that the oxidizing
processes which normally go on in the medulla are prompt-
ly arrested; and it may also be assumed, for sake of argu-
ment, that this arrest of oxidation excites the sense of want
of air. It does not appear how any experiment can be
devised in which the venous blood could be admitted in
such quantity to the medulla, at the same time maintain-
ing the normal supply of oxygen and the uninterrupted
performance of normal oxidation in this particular part.

On the other hand, suppose that the great vessels given
off from the arch of the aorta are tied! While the supply
of fresh arterial blood is thus cut off from the medulla, it
is well known that the contraction of the vessels beyond
the point of ligation, which is slow and gradual, as is char-
acteristic of non-striated muscular tissue, will still force
the small quantity of blood which these vessels contain
through the medulla. My experiments show that the sup-
ply of arterial blood to the medulla need not be very con-

MEDULLA IN NORMAL RESPIRATION 149

siderable in order to satisfy the respiratory sense. Con-
striction of the innominate artery alone does not induce
respiratory efforts. No respiratory efforts are made when
both carotids and both vertebral arteries are constricted.
These efforts, indeed, occur only when the innominate and
the left subclavian are tied, or when ligatures are applied
to both carotids, both vertebrals and both subclavians.

Reasoning from these facts and inferences, the follow-
ing is the only explanation that I can offer of the rapid
excitation of respiratory efforts by simple arrest of artificial
respiration, as compared with the effects of tying the ves-
sels given off from the arch of the aorta:

When artificial respiration is interrupted, the normal
oxidizing process in the medulla oblongata is promptly
arrested and respiratory efforts begin in thirty to forty-
five seconds. When, on the other hand, the vessels which
supply blood to the medulla are tied, the contraction of
the muscular coats of the vessels beyond the points of liga-
tion for a certain time forces a small quantity of arterial
blood to the medulla, and it is only w'hen this ceases that
the want of oxygen is felt. This may be the reason why
the arrest of oxidation in the medulla is later when the
vessels are tied than when artificial respiration is inter-
rupted.

When it is proved, as I think it has been proved con-
clusively, that an animal, after the respiratory movements
have been arrested by artificial respiration, will make re-
spiratory efforts when the supply of oxygen-carrying blood
is shut off from the medulla oblongata, the question arises
in regard to the application of this experimental fact to
the mechanism of normal respiration.

Cause of the Normal Rhythmical Movements of
Respiration. — The normal rhythmical movements of res-
piration are excited and regulated by the respiratory nerve-
centre in the medulla oblongata. Under ordinary physi-
ological conditions the exciting cause of these movements,
whatever it may be, is unconscious; and the muscular acts
by which air is introduced into the lungs take place with-
out efforts of the will. In other words, the movements
of ordinary respiration are unconscious and involuntary.
That these propositions are correct has been proved by
experiments that are perfectly familiar to physiologists.

I50 MEDULLA IN NORMAL RESPIRATION

When all the nerve-centres that are known to have any
relations to sensation and voluntary movements are de-
stroyed, the medulla oblongata remaining intact, the
rhythmical movements of respiration persist. When the
medulla oblongata is destroyed, the other nerve-centres
remaining intact, the respiratory movements are instantly
arrested. The cause of this arrest of respiratory movements
following destruction of the medulla is explained by the
following proposition:

The medulla oblongata contains the only nerve-centre
capable of appreciating the unconscious sense of want of
air; and consequently, when this centre is destroyed, the
sense of want of air is not felt and no true respiratory move-
ments can be excited. In the same way, when oxygen is
freely supplied to the blood of a living animal by artificial
means, no sense of want of air exists and no respiratory
efiforts occur. In the foetus in utero, so long as oxygen
is supplied to the blood by the placenta, no respiratory
efforts are made; but when the placental circulation is in-
terrupted, the sense of want of air is developed and respira-
tory efforts occur. This may take place, as is well known,
before birth.

My experiments published in 1877 show conclusively
that the sense of want of air is developed and respiratory
efforts are excited, not necessarily by a possible irritation
due to the circulation of venous blood in the medulla ob-
longata, but by cutting off from the medulla the supply
of oxygen. This occurs when the respiratory acts have
been arrested by supplying air to the lungs artificially.

Under ordinary physiological conditions, the heart-
beats numbering seventy-two and the respirations eighteen
per minute, the following is probably the mechanism of the
flow of blood through the capillaries of the lungs and the
vessels of the medulla oblongata:

The venous blood from the general system is sent to
the lungs by the action of the right ventricle, the inter-
mittent force of which is absorbed by the elasticity of the
pulmonary artery and its branches, until the current in
the pulmonary capillaries becomes nearly or quite steady
and continuous. This venous blood is poor or deficient in
oxygen and rich in carbonic acid. As it passes through
the lungs it gives off its carbonic acid and takes up oxygen.

MEDULLA IN NORMAL RESPIRATION 151

In the pulmonary vesicles the composition of the air is
tolerably uniform ; that is, it. contains a certain proportion
of oxvgen and of carbonic acid. But at the same time,
the air in the pulmonary cells has a tendency to an increase
in its proportion of carbonic acid with a diminution in its
oxygen; for the venous blood, as it passes through the
pulmonary capillaries, is constantly giving off carbonic acid
and taking up oxygen. This tendency to a diminution in
oxygen and an increase in carbonic acid in the contents of
the air cells progressively increases from the completion of
any single inspiratory act to the beginning of another.
When, however, a new act of inspiration occurs, fresh oxy-
gen is introduced into the lungs, which supplies the place
of a certain quantity of carbonic acid thrown off by the pre-
ceding expiration. That this occurs is sufficiently evident;
and it is illustrated by the fact that when expiration is
voluntarily retarded, the expired air becomes richer in car-
bonic acid and poorer in oxygen than it is under ordinary
conditions.

On the other hand, the left ventricle is sending arterial
blood received from the lungs to all parts of the system,
including the medulla oblongata. The elasticity of the
aorta and of its branches gradually extinguishes or absorbs
the intermittent force of the heart, so that the blood flows
in a steady and continuous stream through the capillaries
of the medulla. But as the tendency of the air in the pul-
monary parenchyma is to progressively increase its pro-
portionate quantity of carbonic acid and to diminish its
oxygen between two inspiratory acts, the tendency of the
blood coming from the lungs and sent by the left ventricle
to the medulla oblongata is to become progressively poorer
in oxygen. After about four revolutions of the heart (as-
suming that the proportion of the beats of the heart to
the respiratory acts is as four to one), the quantity of
oxygen supplied to the medulla oblongata has become so
far diminished that there occurs an unconscious sense of
want of air, and this excites a new inspiratory act. So it
is, in all probabiHty, that the normal, rhythmical acts of
inspiration are periodically excited; and anything, like vio-
lent muscular exercise, that increases the activity of the
consumption of oxygen, of necessity increases the number
of respirations per minute.

152 MEDULLA IN NORMAL RESPIRATION

In my opinion, in the explanation just given of the
cause of the rhythmical acts of respiration, 1 have gone
as far as I can, in the present condition of physiological
knowledge, without becoming involved in unprofitable
speculation and in a discussion of propositions not justified
by established facts. All that can at present be positively
assumed to be true, is that respiratory movements are ex-
cited by a want of oxygen in the substance of the medulla
oblongata; and I know of no reasonable theory that will
explain the exact mode of action of the oxygen of the blood
upon any of the anatomical elements of the respiratory
nerve-centre. Still it may not be uninteresting to refer
to an explanation, proposed by Pfliiger * in 1868 and ad-
vanced again in 1878 by Burkart, the substance of which
is contained in the following quotation:

" I. The ganglionic cells of the respiratory centre produce,
when there is a deficiency of oxygen, a readily oxidizable sub-
stance. 2. This substance performs its function, through a certain
degree of production and accumulation, as a stimulus to the very
cells that are concerned in its production. 3. The oxygen of the
blood, that is of the tissues, operates against the production and
accumulation, and consequently the stimulating action of this hypo-
thetical substance thus restrained or removed. The capacity of the
ganglionic cells to produce, in a greater or less degree, by a defi--
ciency of oxygen, this substance which excites respiratory move-
ments, is measured by the vital energy of the cells, as far as this
vital energy, or better the energy of the process of oxidation, re-
lates to the demand for oxygen on the part of the cells. The pro-
duction of the hypothetical substance is merely the vital expression
of the ganglionic cells of the respiratory centre through a deficiency
in oxygen, and it ceases with the life of the cells themselves." f

The above quotation, which it was somewhat difficult
to render into idiomatic English, embodies a theory which
may be more clearly expressed as follows:

The nerve-cells of the respiratory centre are constantly
producing a hypothetical substance which acts as a stimu-
lus to the muscles of inspiration. As the arterial blood
passes through the capillaries of the medulla, its oxygen
combines with this hypothetical substance, which is thus

* Pfliiger, " Ueber die Ursache der Athembewegungen, sowie der Dyspnoe
und Apnoe." — " Archiv fur die gesammte Physiologie," Bonn, 1868, Bd. i.,
S. go.

f Burkart, " Studien iiber die automatische Thatigkeit des Athemcentrums
und iiber die Beziehungen desselben zum Nervus Vagus und anderen Athem-
nerven." — " Archiv filr die gesammte Physiologie," Bonn, 1878, Bd. xvi., S. 436.

MEDULLA IN NORMAL RESPIRATION 153

destroyed, or at least its action as a stimulus to the mus-
cles of respiration is arrested. The quantity of this sub-
stance existing in the cells of the medulla is regulated by
the supply of oxygen, and this regulates the degree of
stimulation of the respiratory muscles. The production of
this hypothetical substance is a manifestation of the vital
energy of the cells, and this production ceases with the
life of the cells.

The theory which I have proposed involves the follow-
ing simple propositions, deduced mainly from my experi-
ments published in 1877:

1. When the respiratory nerve-centre is fully supplied
with oxygen by means of artificial respiration, this centre
gives ofif no stimulus to the muscles of inspiration and no
respiratory efiforts occur.

2. When there is a deficiency in the supply of oxygen
to the respiratory nerve-centre, the stimulus which gives
rise to inspiratory efforts is generated; and this stimulus
and the respiratory efforts which follow are active and
vigorous in proportion to the extent and duration of the
deficiency of oxygen.

3. In normal respiration, expiration being mainly pas-
sive, the rhythm and extent of the inspiratory acts are regu-
lated by the quantity of oxygen supplied to the medulla
oblongata. Thus, when there is a tendency to a deficiency
of oxygen in the arterial blood, as its proportion must
gradually and progressively diminish from the end of one
inspiratory act to the beginning of another, this need of
oxygen, or unconscious sense of want of air, induces a
stimulus which leads to the introduction of fresh air into
the lungs.

4. As oxygen can get to the medulla oblongata only
through the blood, serious disturbances of the circulation
are always attended with an exaggeration of the respira-
tory sense, although the lungs may be freely supplied with
pure air.

The theory of Burkart involves the assumption of the
existence of a " readily oxidizable substance " which the
cells of the medulla oblongata have a constant tendency
to produce and which the oxygen of the blood has a con-
stant tendency to destroy. Burkart assumes that this hy-
pothetical substance acts as a stimulus to the muscles of

154 MEDULLA IN NORMAL RESPIRATION

inspiration; I contend that it is not logical to go farther
in an explanation of the generation of the respiratory stim-
ulus than to state the fact, which I have demonstrated
experimentally, that the sense of want of air, be it uncon-
scious, as in ordinary respiration, or conscious, as it is when
it becomes a sense of sufifocation, is due to a deficiency
in the supply of oxygen to the respiratory nerve-centre.

Cause of the Conscious and Exaggerated Move-
ments OF Respiration in Dyspncea. — In ordinary respi-
ration, the sense of want of air, which is the starting point
of the stimulus that gives rise to the respiratory acts, is
entirely unconscious, and the acts of inspiration are in-
voluntary and automatic. Even when there is a slight
deficiency in the proper aeration of the blood, as occurs
from the vitiated atmosphere of a crowded room, one ex-
periences merely an indefinite sense of oppression, and the
respiratory movements are still of the same involuntary
character. But when there occurs any serious interference
with the passage of fresh air to the pulmonary vesicles
or an obstruction to the flow of arterial blood to the me-
dulla oblongata, as in certain pulmonary and cardiac dis-
eases, the sense of want of air is exaggerated until it be-
comes a consciousness of pulmonary oppression or impend-
ing suffocation. Under such conditions many muscles that
are not usually brought into action in inspiration are used,
partly by an effort of the will. This is simply an exaltation
and extension of the normal respiratory sense, so that it
reaches the true centres of sensation, causing a voluntary
increase in the number and extent of the inspiratory acts.
The sense of suffocation, indeed, differs from the normal
unconscious respiratory sense merely in degree and in the
fact that the former operates on the centres of ordinary
sensation through sensory nerves, while the latter is con-
fined to the medulla oblongata. Having once ascertained
definitely the cause of the normal sense of want of air, one
can readily understand how an exaggeration of the condi-
tions which give rise to the natural automatic movements
of respiration may produce those sensations which attend
the various degrees of suffocation. As more remote con-
sequences of asphyxia, there occur insensibility, an arrest
of the circulation by engorgement of the heart and finally
the sensibility of the medulla oblongata disappears. As

MEDULLA IN NORMAL RESPIRATION 155

a general rule, when the action of the heart has ceased from
asphyxia, even the most efficient artificial respiration fails
to restore the respiratory function, for the reason that it is
only by the action of the heart that blood can be sent to
the medulla. While, however, the heart continues to act,
although its contractions may be very feeble, it is within
the limits of possibiHty to revive the functions of the me-
dulla by artificial respiration.

There are certain agents which seem to affect the me-
dulla directly, such as narcotics and anesthetics. In poi-
soning by opium the frequency of the respiratory acts is
diminished and they may be arrested. All experimenters
must have frequently observed arrest of respiration by the
administration of anaesthetics to animals. In such in-
stances, if the heart continues to beat, it generally is pos-
sible to revive the respiratory function by artificial insuffla-
tion of the lungs. In most cases of suspended respiratory
action from any temporary cause, although electricity, sud-
den and active stimulation of the surface, etc., may aid in
restoration, the main reliance should be upon persistent and
efficient artificial respiration.

Cause of the First Respiratory Act after Birth
AND OF Respiratory Efforts in Utero. — No one
doubts, at the present day, that the blood from the placenta
furnishes to the foetus in utero all the oxygen demanded
for the function of respiration; and it is unnecessary to
cite authorities to show that the blood of the umbilical
vein contains oxygen, as this fact has long since been es-
tablished. If the uterus of an animal far advanced in ges-
tation is opened, an experiment which I have frequently
made on cats and dogs, the foetuses for a time will make
no respiratory efforts; but compression of the umbilical
vessels of one will cause it to make very violent move-
ments of inspiration, while the others will remain quiet
so long as the placental circulation is not interrupted. The
umbilical vein carries its blood to the vena cava ascendens,
thence to the left side of the heart through the foramen
ovale, and thence to the upper extremities and head, in-
cluding, of course, the medulla oblongata. Thus the blood
that is most highly oxygenated is supplied to the medulla;
and the aorta below the arch receives, through the ductus
arteriosus, the blood from the right ventricle, which con-

156 MEDULLA IN NORMAL RESPIRATION

tains a much smaller quantity of oxygen than the blood
distributed through the vessels given off above. Cutting
off the flow^ of blood from the placenta is almost equivalent,
therefore, to tying the vessels of the arch of the aorta.
When this is done, the flow of oxygenated blood to the
medulla is arrested; and there follows a sense of want of
air which induces a stimulus that is sent to the muscles
of inspiration. Air is then for the first time taken into
the lungs, and the conditions of the circulation are changed.
The lungs are now distended with air, and the pulmonary
vessels are dilated, so that the right ventricle supplies the
pulmonary capillaries, instead of sending the venous blood,
as before, in greatest part through the ductus arteriosus.
The pulmonary circulation being thus established, the con-
ditions rapidly assume the character observed in the adult.
It is evident, from the experiments already noted show-
ing the effects of compression of the umbilical vessels, that
an abnormal condition in utero, in which there is serious
interference with the placental circulation, may induce in-
spiratory efforts in the foetus, and that the liquor amnii may
thus find its way into the air-passages.

ARE THE NORMAL RESPIRATORY MOVEMENTS EITHER EN-
TIRELY OR IN PART REFLEX, IN THE SENSE IN WHICH
THE TERM REFLEX IS ORDINARILY UNDERSTOOD BY
PHYSIOLOGISTS?

This question is one which naturally arises as a logical
sequence of the experiments I have described and of the
deductions that I have drawn from the ascertained facts.
The most important of these facts is the following: When
the medulla oblongata is freely supplied with oxygen-car-
rying blood in a living animal, this being effected by arti-
ficial insufflation of the lungs, there are no inspiratory
efforts. The animal makes respiratory efforts as the supply
of oxygen to the medulla diminishes; and the want of oxy-
gen alone is capable of inducing the stimulus to the mus-
cles which gives rise to the efforts to introduce air into
the lungs. It is evident that the stimulus, under these
experimental conditions, which was formerly thought to
be reflex and produced by a certain impression conveyed
to the medulla by centripetal nerves, really takes its origin

MEDULLA IN NORMAL RESPIRATION 157

in the medulla itself; that the respiratory sense, so called,
is due to some alteration in the conditions of the medulla,
which depends upon the supply of oxygen-carrying blood;
and finally, that this alteration does not of necessity in-
volve any impression received through afferent nerves.
Viewed in this way, when a living animal, in which the
respiratory movements have been for the time arrested by
artificial insufflation of the lungs, makes inspiratory efforts
following the operation of shutting off the blood-supply
from the medulla, the stimulus which gives rise to these
efforts can not properly be called reflex.

I shall leave out of the question under consideration
various modifications of the respiratory acts, such as
coughing, sneezing, etc., and the influence of certain un-
usual impressions made upon the surface, as by a cold
douche, restricting the discussion to the normal respiratory
movements.

It is well known that a relatively strong electric current
applied to the pneumogastric nerves in the neck or to cer-
tain branches of the pneumogastrics, the superior and the
inferior laryngeals, will instantly arrest respiration. This
action is reflex, as is shown by the fact that stimulation
of the central ends of the divided nerves influences respira-
tion, while the stimulus applied to the peripheral ends has
no effect. The effect of powerful electric stimulation of
the pneumogastrics and of certain of their branches is
marked and constant; at the same time, stimulation of
some of the nerves of general sensibility has been observed
to arrest respiratory movements, although this result is
not invariable. When the respiratory movements are com-
pletely arrested by faradization of the pneumogastrics, it
is always the same for the general movements of the ani-
mal, which remains motionless.* On the other hand, " a
feeble excitation accelerates the respiration; a more power-
ful excitation retards it; a very powerful excitation arrests
it. These words ' feeble ' and ' powerful ' having, it is un-
derstood, only a relative sense for any one animal, and
tmder certain conditions: what is feeble for one would be
powerful for another, etc." f

* Bert, " Legons sur la physiologic comparee de la respiration," Paris, 1870,
p. 490.

t Bert, loc. cit.

158 MEDULLA IN NORMAL RESPIRATION

So far as these experimental facts can be applied to the
physiology of ordinary respiration, it seems that the nerves,
the action of which is brought into play under physiological
conditions, must be mainly if not exclusively the pneumo-
gastrics. These nerves have their origin at the medulla
oblongata, which undoubtedly contains the sole respiratory
nerve-centre; they are distributed to the entire respiratory
apparatus from the larynx to the deepest parts of the lungs;
they are the only nerves belonging to the cerebro-spinal
system that are distributed to the larynx, trachea, bronchia
and the pulmonary parenchyma; while they are not distrib-
uted to the respiratory muscles, except the intrinsic mus-
cles of the larynx, they are capable, by reflex action, of
exerting a very marked influence over the respiratory
movements. In discussing, then, the question of reflex
nervous action in normal respiration, the argument may
properly be confined to the pneumogastrics.

The curious and interesting respiratory phenomena ob-
served in living animals after section of both pneumogas-
trics are very important. When both pneumogastrics are
divided in the neck, the excitation directly produced by
their section momentarily accelerates the respiratory move-
ments. In very young animals, in which the cartilages of
the larynx are comparatively soft and pliable, the paral-
ysis of the inferior laryngeal nerves, which preside over the
respiratory movements of the glottis, often produces speedy
suffocation from closure of the glottis during the inspira-
tory act ; but in most adult animals the walls of the larynx
are sufficiently rigid to enable the acts of inspiration to be
carried on without serious obstruction. In such animals,
for a few seconds, the number of respiratory acts may be
increased; but so soon as they become tranquil, the num-
ber is very much diminished and the movements change
their character. The inspiratory acts become unusually
profound and are attended with excessive dilatation of
the thorax. Under these conditions I have seen the num-
ber of respirations fall from sixteen or eighteen to four
per minute.

In discussing the possible reflex influences upon the
normal respiratory movements which may operate through
the pneumogastrics, I shall make use of a very interesting
suggestion made by Rosenbach, in 1878. In a brief note

MEDULLA IN NORMAL RESPIRATION 159

upon the " Influence of Stimulation of the Vagus upon
Respiration," Rosenbach proposes the theory that this
nerve (the vagus) is the vasomotor nerve of the medulla
oblongata, and that it contains fibres which contract, and
fibres which dilate the bloodvessels. This idea is presented
by Rosenbach simply as an hypothesis, which he " hopes
later to be able to establish by experiments." *

I may now state, in continuing my argument, the fol-
lowing propositions, all of which, except the last, I assume
to be facts that have been established experimentally:

I. A deficiency in the quantity of oxygen supplied to
the medulla oblongata through the arterial blood circu-
lating in its substance will of itself give rise to a stimula-
tion of the muscles concerned in the act of inspiration.

II. A relatively feeble electric stimulation of the pneu-
mogastric nerves increases the frec}uency of the inspiratory
acts; a stronger stimulation may diminish their frequency;
and a very powerful stimulation arrests the respiratory
movements. The action in these instances is reflex and
not direct.

III. Section of both pneumogastric nerves in the neck,
in most adult animals, very greatly diminishes the fre-
quency of the respiratory acts.

IV. The pneumogastric nerves possibly contain vaso-
motor filaments that are capable of regulating and modi-
fying the supply of blood to the vessels of the medulla
oblongata.

If these propositions are taken as the basis of a theory
of the mechanism of normal respiration, the following seem
to be the natural and logical conclusions to be drawn from
them:

I. When the action of the medulla oblongata is re-
moved from the influence of the pneumogastric nerves, as
it is after division of both of these nerves in the neck, air
is taken into the lungs when the deficiency of oxygen in
the medulla has reached the point at which the respiratory
sense necessarily generates the stimulus sent to the inspira-
tory muscles. This action is in no sense reflex, and it de-
pends entirely upon the development, de novo, of a stimu-

* Rosenbach, " Notiz liber den Einfluss der Vagusreizung aiif die Ath-
miing." — " Archiv fiir die gesammte Physiologic," Bonn, 1878, Bd. xvi., S. 503.

i6o MEDULLA IN NORMAL RESPIRATION

lation or an irritation in the medulla itself. Under these
conditions the acts of inspiration are abnormally infrequent
and they become excessively prolonged and profound.

n. In normal respiration, however, it is certain that im-
portant reflex influences operate upon the medulla ob-
longata through the pneumogastric nerves. While there
can be no doubt that the stimulus which gives rise to in-
spiratory efforts is due purely and simply to want of oxy-
gen in the medulla, in order that this stimulus shall operate
in accordance with the requirements of the system for
oxygen, producing normally sixteen to twenty inspirations
per minute and varying the number of these movements
with different physiological conditions of the organism,
depending upon muscular exercise, etc., it is necessary that
the respiratory acts should be regulated through the nerv-
ous system. Inasmuch as the respiratory acts involve the
contraction of striated muscular fibres, it would be ex-
pected that the nerves which regulate them should belong
to the cerebro-spinal system. In studying experiment-
ally the influence of various nerves on the respiratory
movements, it is found that the pneumogastrics, which
arise from the medulla and are distributed largely to the
respiratory apparatus, are closely connected with certain
artificially-induced modifications of respiratory action. By
applying to these nerves electric stimulation of different
degrees of intensity, the respiratory movements may be in-
creased or diminished in frequency or they may be arrested,
and these phenomena are always reflex.

III. Section of both pneumogastric nerves seems to re-
move the medulla oblongata, so far as its action as a re-
spiratory nervous centre is concerned, from the reflex action
of the nervous system; and the respiratory acts then be-
come so far diminished in frequency and are so laboured
as to produce serious pulmonary lesions. It is probable
that death occurs in a few days after this operation, not
alone from abnormal respiratory action but from a sus-
pension of other important functions which the pneumo-
gastrics have to perform. It is possible, also, that some
of the phenomena that are observed in narcotic poison-
ing, notably the great diminution in the number of respira-
tory movements, are due to an interference wdth the re-
spiratory functions of the pneumogastrics.

MEDULLA IN NORMAL RESPIRATION i6i

The precise mechanism of the action of the pneumogas-
trics in normal respiration and the exact seat and character
of the impressions which serve as the starting point in the
reflex phenomena observed, it is difficult to describe within
the limits of ascertained facts. If the theory advanced by
Rosenbach is accepted; viz., that the pneumogastrics con-
tain vasomotor filaments which regulate the quantity of
blood passing through the medulla oblongata, the mechan-
ism of the action which takes place in the respiratory
nerve-centre is readily understood; but the seat and the
exact nature of the impression which gives rise to these re-
flex changes in the calibre of the vessels are still a matter
of speculation and conjecture. So far as muscular action
in tranquil respiration is concerned, it is necessary to con-
sider only the acts of inspiration, for expiration is produced
mainly by the passive reaction of the walls of the thorax
and by the resiliency of the elastic pulmonary parenchyma
succeeding the action of the muscles which enlarge the
chest and inflate the lungs.

Finally, the respiratory sense, " besoin de respirer,"
sense of want of air, or the stimulus which gives rise to in-
spiratory efforts, is due purely and simply to a deficiency
in oxygen in the medulla oblongata, in which is contained
the sole respiratory nerve-centre. The frequency and the
extent of the normal inspiratory movements are regu-
lated and accommodated to the physiological requirements
of the system by reflex action operating through the pneu-
mogastric nerves.

In this article I have endeavored to set forth the na-
ture and the physiological bearings of my experiments,
published in 1877, showing that the sense of want of air is
due primarily to a deficiency of oxygen in the medulla
oblongata. I have attempted, also, to show how the oper-
ation of the stimulus to the inspiratory muscles, which is
due to this deficiency of oxygen in the medulla, is regu-
lated, in normal respiration, by reflex action through the
pneumogastric nerves. Physiologists are now well ac-
quainted with the action of the pneumogastrics in connec-
tion with the circulation, the action of the stomach and
intestines and certain functions of the liver; but the action
of these nerves in normal respiration and the causes of the
II

i62 MEDULLA IN NORMAL RESPIRATION

respiratory phenomena following their stimulation and
their section have heretofore been obscure. I venture to
hope that my discussion of the reiiex function of the pneu-
mogastrics in connection with the respiratory movements
has^thrown some light upon questions which have not been
satisfactorily answered by physiologists.

IX

EXPERIMENTAL RESEARCHES INTO A NEW
EXCRETORY FUNCTION OF THE LIVER;
CONSISTING IN THE REMOVAL OF CHO-
LESTERIN FROM THE BLOOD, AND ITS
DISCHARGE FROM THE BODY IN THE FORM
OF STERCORIN. (THE SEROLINE OF BOU-
DET.)*

ILLUSTRATED BY THREE PLATES CONTAINING FIFTEEN

FIGURES

Published in the "American Journal of the Medical Sciences"
for October, 1862.

" La cholesterine du sang est elle un de ces produits destines
a etre expulses de I'economie, et, par consequent, depotirvus d'ac-
tion immediate sur I'economie elle meme ? Sa destination est tout
a fait inconnue." " Traite de physiologie," par F. A. Longet.
Paris, 1861. Tome i., p. 488.

This sentence, which is taken from the most elaborate
treatise on physiolog)^ in any language, published at the
centre of physiological science, in 1861, expresses the state
of our knowledge in regard to the function of choles-
terin. Cholesterin was discovered in 1782, by Poulletier
de la Salle, in biliary calculi, and was detected upwards of
thirty years ago in the blood by Denis; but since then, with
the exception of researches of a purely chemical nature
into its properties, our knowledge in regard to it has
not advanced. Its chemical history even, is far from per-
fect; while its physiological history is unknown. In 1833

* A French translation of this essay was published in Paris in l868, and in
i86g received an "honorable mention" with a "recompense" of 1,500 francs
from the Institute of France (Academie des Sciences), Concours^ Monthyon
(Medecine et Chirurgie), being second to the essay of Villemin (Etudes sur la
tuberculose, preuves rationnelles et experimentales de sa specificite et de son
inoculabilite), which work received the Monthyon prize for that year.

163

i64 NEW FUNCTION OF THE LIVER

Boiidet discovered a substance in the blood which he called
" seroline "; a principle having many characters in com-
mon with cholesterin, but heretofore interesting merely as
a curious proximate principle, found in excessively minute
quantities in the serum of the blood only (whence its name);
too minute, indeed, for ultimate analysis. Its function was
as obscure as that of cholesterin. In examining the litera-
ture of these two substances, I find that cholesterin is
frequently not treated of in systematic works on physiolo-
gy. Serolin is seldom even mentioned. Their function
has been so obscure and apparently so unimportant, that
theories in regard to it have not been advanced; and
the highest chemical authorities, in speaking of their office
in the economy, simply say of one, as of the other, that it
is unknown. In the " Chimie ana1<Dmique," by Robin and
Verdeil, I find cholesterin summed up in these words:

" Le role physiologique qu'elle remplit dans I'economie est
egalement inconnu."

Of serolin, the same authors say:

" On ne sait pas comment se forme la seroline, ni quel est son
role physiologique."

Though the physiology of these substances is thus ob-
scure, though chemistry has thus far done but little for
their history, and physiology nothing, certain facts with
relation to them would seem to indicate that they are not
unimportant in the economy. Cholesterin is found in the
blood, bile, liver, nervous matter, crystalline lens, meconi-
um (not in the feces, as incorrectly stated by authors),
beside in a number of morbid products. It is found in
these situations constantly; it appears in the blood as soon
as that fluid is found, and continues to the end of life. Its
quantity in the blood is increased in certain diseased condi-
tions and diminished in others. Serolin has been said to
exist constantly in the blood, though, till now, it has never
been discovered in any other situation. It, like cholesterin,
is a constant principle, they having many chemical charac-
ters in common. Their function is definite; it is important;
and, if the writer does not exaggerate this importance in
the enthusiasm of exploring a hitherto absolutely uncul-
tivated field, a knowledge of the functions of these sub-
stances will be of incalculable value to the practical physi-

NEW FUNXTION OF THE LIVER 165

cian; and the path thus opened by physiology will lead to
a great field for pathological inquiry. What the discovery
of the function of urea has done for diseases which now
come under the head of uremia, the discovery of the func-
tion of cholesterin may do for the obscure diseases which
may hereafter be classed under the head of cholesteremia.

It is not surprising that the function of substances —
which have been isolated with great difficulty, which have
never been found in any of the excretions, which exist in
quantity so small that their investigation seemed to belong
especially to the chemist, physiologists having been dis-
couraged, perhaps, from studying them — should be thus
obscure. But it is surprising that an important fluid, the
bile, the product of the largest gland in the economy and
the one most constantly found in the animal scale, should
be so little understood. This has been regarded by some
as a simple excrement, and by others as not an excrementi-
tious, but a digestive fluid; and so much labor has been
expended by physiologists in endeavors to settle this
point, that no one has pretended to give an account of
its excrementitious function, if it has any, and researches
into its digestive function have left us almost entirely in
the dark. Blondlot reported an observation on a dog
that lived for five years with a biliary fistula diverting,
as it is stated, all the bile from the intestines and discharg-
ing it from the body. The animal presented no untoward
symptoms, died a natural death, no bile found its way into
the intestines, but it was all discharged. According to
this observation, the bile would appear to be purely an
excretion. Schwann, and Bidder and Schmidt, in a large
number of experiments, never succeeded in keeping a dog
operated on in this w^ay for more than a few^ weeks; they
all died with evidences of inanition. The bile, according
to these observations, is concerned chiefly in nutrition; and
as it is poured into the upper part of the digestive tube,
it is important, probably, in digestion. But Bidder and
Schmidt do not satisfy us w^hat its digestive function is;
nor does Blondlot say what principle is excreted by it or
what would be the result of its suppression.

Aside from a few isolated facts, interesting enough,
but indicating nothing definite, this is all w^e know of the
function of the bile. But what physiologist does not feel

i66 NEW FUNCTION OF THE LIVER

this hiatus in his science; or what practical physician does
not feel and know the importance of the function of the
bile! It needs no inquiry into natural history, showing thq
universality, almost, of the liver in the animal scale, to im-
press upon the physician at the bedside the importance of
the bile. A patient is suffering from an obscure ailment,
which he may call biliousness or derangement of the liver,
and which, in some unexplained way, is relieved by a mer-
curial purge. The practitioner knows that the bile-secret-
ing function of the liver is important, but does not learn it
from the physiologist. Every practitioner must feel that
the liver has a function which must be explained him by
the physiologist, before he can avoid treating a large class
of diseases empirically.

The bile has an important excretory function, which is
liable to many disorders; and this function I hope to be
able, in the present article, to describe.

It is evident from the preceding remarks that the physi-
ological history of the bile remains to. be written. The
subject is too interesting and important not to engage the
mind of the experimental physiologist. It is difficult at
first sight to harmonize statements, to which reference
has just been made, of experimenters, equally entitled to
consideration, which are diametrically opposite. But of
course the philosophical method of studying the bile is first
to settle w^iether it is excrementitious or recrementitious.
If the former, what substance is excreted, and where is it
formed? If the latter, what function does it perform in
any of the processes of nutrition. With the view to har-
monize, if possible, in my own mind, the opposite state-
ments of Bidder and Schmidt and of Blondlot, I attempted
some time ago to establish biliary fistulre in dogs. The
first experiments were made in New Orleans in the winter
of 1860-61, but were all of them unsuccessful, no animal
surviving the operation more than three days. The ex-
periments were discontinued at that time but were renewed
in the winter of 1861-62 at the Bellevue Hospital Medical
College. After a number of trials which were no more
successful than those made the previous winter, I succeed-
ed in performing the operation with considerable rapidity
and with very little disturbance of the abdominal organs,
and in one animal the success was complete.

NEW FUNCTION OF THE LIVER 167

Experiment I. — The operation was performed by making an
incision into the abdomen in the median line just below the ensi-
form cartilage, about three inches in length. The edge of the liver
was carefully raised, the bile duct isolated, and two ligatures ap-
plied, one next the duodenum and the other near the junction of
the ductus choledochus with the cystic duct, the intermediate por-
tion being excised. The fundus of the gall-bladder was then drawn
to the upper part of the wound, an incision made in it of about
an inch in length, the bile evacuated, and the edges attached to
the skin by points of interrupted suture. The wound was then
carefully closed around the opening into the gall-bladder.

This is nearly the proceeding recommended by Blondlot, who
prefers, however, to operate while the animal is fasting, as the
gall-bladder is then distended and can be easily found. I have
preferred to operate after feeding, when the gall-bladder is com-
paratively empty, as there is no great difificulty in finding it, and
in evacuating its contents less bile is likely to find its way into the
peritoneal cavity, which is one of the causes of the intense peri-
tonitis which follows this operation.

The animal ate well the day after the operation, the bile flowed
freely from the fistula and was entirely cut off from the intestine,
as shown by post-mortem examination. No symptoms supervened
except those produced by the diversion of the bile from its normal
course. This operation was performed on the 15th of November,
1861, and the animal lived thirty-eight days.

In no observation that I have found recorded has the animal
been so free from inflammation consequent upon so serious an
operation ; and this seemed a most favorable opportunity for de-
termining whether an animal could live with the bile shut off from
the intestinal tube and discharged by a fistula. In this case the
animal gradually lost flesh and strength, his appetite becoming
voracious, until finally he died of inanition ; the observation agree-
ing in every important particular with the experiments of Schwann,
and of Bidder and Schmidt.

Experiment II. — This experiment was undertaken to ascer-
tain, if possible, the entire quantity of bile secreted in twenty-
four hours. A fistula was made into the ductus communis chole-
dochus, the duct being divided and a silver tube introduced. The
experiment did not succeed in the point of view in which it was
undertaken, and about forty-eight hours after the operation, the
tube dropped out. After the removal of the tube the bile ceased
to flow externally, and the animal did not appear to suffer any bad
effects from the experiment. Thirty days after the operation, the
animal having entirely recovered, he was killed by section of the
medulla oblongata, and the parts carefully examined. The post-
mortem examination I transcribe from my note-book.

" On post-mortem examination the liver was found adherent
to the diaphragm over the greater part of its convex surface.
There were evidences of limited inflammation over the duodenum.
The liver itself was normal. Upon opening the duodenum, the
papillae which marks the opening of the ductus communis chole-

i68 NEW FUNCTION OF THE LIVER

dochus was normal in appearance. A small silver stilet was in-
troduced into the duct. For a long time it was impossible to find
any communication between the upper part of the duct and the
intestine; but at last, after patient searching (knowing that no bile
was discharged from the body and that it was absolutely certain
that a communication existed with the duodenum), a communica-
tion was found. In Blondlot's case there probably was a commu-
nication reestablished which escaped his observation."

In the remarkable observation reported l)y Blondlot,.
in which the animal survived for so long a period, the suc-
cess is attributed to the fact that the dog was prevented
from licking the bile as it flowed from the fistula, Blondlot
stating that so soon as the animal was prevented from lick-
ing the bile, nutrition began to improve. Anxious tO'
carry out all the precautions which had been adopted, I
so muzzled the animal in Experiment I., covering the lower
part of the muzzle with oiled silk, that it was impossible
for him to swallow a drop of the bile. This muzzle was
kept on till the death of the animal, but the proceeding
had no effect on his nutrition. The bile flowed so freely
from the fistula that all the lower part of the animal was
covered with it. It was not, however, until I made the
post-mortem examination in the second experiment that
I was able to see the difficulty which I had experienced
in harmonizing the observations of the different experi-
menters I have quoted. In the lower animals — in dogs,
at least — ducts have a remarkable tendency to reestablish
themselves. Any one who has operated much upon the
glands can hardly fail to have noticed this fact. The pan-
creatic duct, for example, after having been divided and
a tube introduced, invariably becomes reestablished after
the simple removal or dropping out of the tube. It was
so in Experiment II., in which the tube dropped out of
the bile duct. The duct undoubtedly became reestab-
lished, for no bile flowed externally for nearly a month, the
animal enjoying perfect health, and the fluid necessarily
being emptied into the intestine; yet it was with the great-
est difficulty that the communication could be found with
the probe, and it was only after long searching, knowing
that there must be a communication, that it was discovered
at all. Taking into consideration the great difficulty I had
in finding the passage in this instance, and after having
carefully examined the case reported by Blondlot, I have

NEW FUNCTION OF THE LIVER 169

concluded that a communication existed in his experiment
which escaped observation, but by means of which a large
quantity of bile found its way into the intestine/'^

In regard to the digestive function of the bile, it is
sufficient to state here that the experiments which I have
made on this subject have led me to believe that this fluid
has an important ofifice in connection with the function
of digestion — one, indeed, which is essential to life. The
nature of its of^ce, however, is not understood and can
be settled only by a long and carefully executed series of
experimental researches which would probably involve the
whole subject of digestion. This I hope to be able to pre-
sent in another paper. There is, however, another function
of the bile entirely distinct from the preceding. It is the
separation from the blood of cholesterin, an excremen-
titious substance, which is formed by the destructive as-
similation of certain tissues of the body. Though not dis-
charged from the body as cholesterin, it being first changed
into another substance, it is separated in that form from
the blood and poured into the intestine by the ductus com-
munis choledochus. This new excretory function of the
bile will form a great part of the subject of this paper; the
recrementitious function, which is necessary to complete
the physiological history of this fluid, being deferred.

It will be found that cholesterin is the most important
excretion separated by the liver, as urea is the most im-
portant excretion separated by the kidneys; and the study
of this substance will necessarily involve the depurative
function of the liver. I shall therefore begin with choles-
terin, and endeavor to show where it is formed in the
economy, by following the blood in its passage through
various organs. This will necessarily involve a description
of the chemical processes which have been employed in
its extraction. I shall then endeavor to show where the

* An account of this experiment is to be found in an article entitled " Essai
sur les fonctions du foi et de ses annexes," par N. Blondlot, 1846. The post-
mortem examination of the animal, made more than five years after the estab-
lishment of the fistula, was published in a little memoir complementary to the
preceding, entitled " Inutilite de la bile dans la digestion," 1851. It is not
contemplated to enter into a full discussion of the views of Blondlot and others
on the uses of the bile in digestion. That subject will be taken up in another
paper in which mainly the digestive properties of the bile will be considered.
In this connection it is proposed to take up only the excrementitious function
of the bile.

I70 NEW FUNCTION OF THE LIVER

cholesterin is removed from the blood, by the same method
of investigation. The next step will be to follow it out
of the body and study the change which it undergoes in
its passage through the alimentary canal. Having de-
scribed the process of formation in the tissues, separation
from the blood by the liver and final discharge from the
body, 1 shall endeavor to show, finally, the effects of in-
terruption of this function of the liver upon the economy.
This will lead into j^athology, and a host of diseases will
arise which may be dependent on a disturbance of the ex-
cretory function of the liver. I shall be enabled to draw
the line more closely between conditions in which there
is resorption simply of the innocuous coloring matter of
the bile, and those diseases in which there is a failure to
separate the excretions from the blood. These conditions,
it is well known, are widely different as to gravity, and
the distinction between them is of great importance. The
latter condition, characterized by the retention of choles-
terin in the blood, will be treated of under the name of
■cholesteremia.

CHOLESTERIN

Chemical Characters. — Cholesterin is a non-nitro-
genous substance, having all the properties of the fats,
excepting that of saponification with the alkalies. Its
chemical formula is usually given as C25H22O. It belongs
to a class of fatty substances which are non-saponifiable,
which have been grouped by Lehmann under the name
of lipoids. This class is composed of cholesterin and sero-
lin, which are animal substances; castorin, from the cas-
toreum, and ambrein, from amber. To this he adds a sub-
stance discovered in a uterine tumor by Busch, called
inosterin. Cholesterin is neutral, inodorous, crystalliza-
ble, insoluble in water, soluble in ether, very soluble in hot
alcohol, though sparingly soluble in cold. It burns with a
bright flame, but is not attacked by the alkalies, even after
prolonged boiling. When treated with strong sulphuric
acid, it strikes a peculiar red color, which is mentioned by
•some as characteristic of cholesterin. I have found that it
possesses this character in common with serolin.*

* This reaction of serolin is mentioned by Berard, in his " Cours de
physiologic," tome iii., p. 117.

NEW FUNCTION OF THE LIVER 171

Forms of its Crystals. — Cholesterin may easily and
certainly be recognized by the form of its crystals, the
characters of which can be made out by means of the mi-
croscope. They are rectangular or rhomboidal, exceeding-
ly thin and transparent, of variable size, with distinct and
generally regular borders, and frequently arranged in layers
with the borders of the lower crystals showing through
those which are superimposed. This arrangement of the
crystals takes place when cholesterin is present in con-
siderable quantity. In pathological specimens they gen-
erally are few in number and isolated. The plates of cho-
lesterin are frequently marked by a cleavage at one corner,
the lines running parallel to the borders; frequently they
are broken, and the line of fracture is generally undulat-
ing. Lehmann attaches a great deal of importance to
measurements of the angles of the rhomboid. According
to this author, the obtuse angles are 100° 30', and the
acute 79° 30'. I have lately examined a great number of
specimens of cholesterin, extracted from the blood, bile,
brain, liver, and occurring in tumors, and am confident
that the crystals have no definite angle. Frequently the
plates are rectangular, and sometimes almost lozenge-
shaped. It is by the transparency of the plates, the paral-
lelism of their borders, and their tendency to break in
parallel lines that we recognize them as formed of choles-
terin. Lehmann seems to consider the tablets of this sub-
stance as regular crystals having invariable angles. From
examination during crystallization, I am disposed to think
that they are not crystals but fragments of micaceous
sheets, which, from their extreme tenuity, are easily broken.
In examining a specimen from the meconium, wdiich I
extracted with hot alcohol, I was able to see a transparent
film forming on the surface of the alcohol soon after it
cooled; this, on microscopic examination, in situ, disturb-
ing the fluid as little as possible, was found to be marked
by long and parallel lines. When the fluid had partially
evaporated, it became broken and took the form of the
ordinary crystals of cholesterin, but they were larger and
more regular. The beauty of the tablets at this stage
could not be adequately represented. They were exceed-
ingly thin, and regularly divided into delicate plates, with
the characteristic corner cleavages of cholesterin; and

172 NEW FUNCTION OF THE LIVER

as the focus of the instrument was chanq-ed, new layers,
with different arrangement, were brought into view. I
have attempted to give an idea of the form of these tal)lets
in Fig. I ; but it is, of course, impossible to represent their
pale, but beautifully distinct borders. As has been re-
marked by Rol)in, the borders of these crystals can be but
imperfectly imitated by a line; there is no line in the ob-
ject itself, but the edge shows where the tablet ceases.
(See Fig. i.)

The crystals generally are colorless, but when present
in colored fluids, may take a yellowish tint or even be-
come very dark. They may still be recognized, however,
by the characters of form just described.

Crystals of cholesterin melt at 293° Fahr., but are
formed again when the temperature falls below that point.
According to Lehmann, they may be distilled in vacuo at
680° without decomposition. The determination of the
fusing point is one of the means of distinguishing it from
serolin, which fuses at 90.8°.

Situations of Cholesterin. — Most authors state
that cholesterin is found in the bile, blood, liver, brain
and nerves, crystalline lens, meconium and the fecal mat-
ter. I have found the cholesterin in all these situations
invariably, excepting the feces, where it was seen but once
after a number of examinations; and in studying the works
of those who have investigated this substance, I can find
no one who has found it in the normal feces. It is found
in large quantities in the meconium, from which, perhaps,
it is most easily extracted in a state of purity, and has been
extracted from the feces of animals in a state of hiberna-
tion; but though it may occasionally be found in the feces
in disease and in animals after long fasting, I am confident
that it never occurs under ordinary conditions. The anal-
ysis of the fecal matter is so unattractive that it has been
very much neglected by chemists; and until a few years
ago, when an elaborate analysis was made by Marcet, to
which reference will hereafter be made, the analyses of
Berzelius furnished nearly all our data on this subject. Cho-
lesterin forms the greatest part of biliary calculi, which in-
deed consist generally of nothing but cholesterin, coloring
matter and mucus. It is found in a large number of mor-
bid deposits. Few specimens of cancer are examined with-

NEW FUNCTION OF THE LIVER

173

out discovering tablets of cholesterin. It is very abundant
in encysted tumors. According to Robin, atheromatous
deposits, which are found in the middle coats of the arteries,
are often composed of cholesterin. It sometimes forms
distinct tumors or deposits in the substance of the brain.
I lately had an opportunity of examining a tumor from
"the brain, at the Belle vue Hospital, which consisted of
nearly pure cholesterin. It has often been found in the
fluid of hydrocele, in the fluid of ovarian cysts, in crude
tubercle, in epithelial tumors and in pus. The propor-
tion in which it exists in the fluids of the body is very small.
I have made a number of quantitative analyses of the blood,
the results of which I give in the following table with some
other analyses which have been made for this substance.
I also give the quantity which I have found in the other
situations in which it exists. The variations in dififerent
parts of the circulation and in diseased conditions will be
given in another table. The quantity in the brain and
crystalline lens has, I believe, never before been estimated:

Table of Quantity of Cholesterin in Various Situations

Situation.

Venous blood (male)

" (female). . . . .

" (male set. 35)

" (male set. 22)

" (male set. 24)

Bile (human)

" (normal, of ox)

" (human)

Meconium

Brain (human) ,

■Crystalline lens (ox) *

Observer.

Becquerel and Rodier.

Becquerel and Rodier.

Flint.

Flint.

Flint.

Frerichs.

Berzelius.

Flint.

Simon.

Flint.

Flint.

Flint.

Flint.

Quantity
examined.

312. 0S3

187.843
102.680

224.588
170.541

159-753
150.881
135.020

Cholesterin
per 1,000 pts.

0.090
0.090

0.445
0.653

0.751
I .60a
I .000
0.618
160.000
6.245
7.729
11.456
0.907

Forms under which Cholesterin exists in the
Organism. — In the fluids of the body cholesterin exists
in a state of solution, but by virtue of what constituents
it is held in solution is not entirely settled. It is stated
that the biliary salts have the power of holding it in solu-

* In this examination four fresh crystalline lenses of the ox were used.

174 NEW FUNCTION OF THE LIVER

tion in the bile, and that the small quantity of fatty acids
which are contained in the blood hold it in solution in that
fluid, but direct experiments on this point are wanting.
In the nervous substance and in the crystalline lens it is
united, " molecule a molecule," to the other elements which
go to make up these tissues. After it is discharged into
the intestinal canal, when it is not changed into stercorin,
it is to l)e found in a crystalline form, as in the meconium
and in the feces of animals in a state of hil)ernation. In
pathological fluids and in tumors it is found in a crystal-
line form and may be detected by microscopic examination.

Process for the Extraction of Cholesterin. —
Without describing the processes which have been em-
ployed by other observers for the extraction of cholesterin
from the blood, bile and various tissues of the body, I shall
confine myself to a description of the process which I have
found most convenient to employ in the analyses I have
made for this substance. In analyses of gall-stones the
process is very simple; all that is necessary being to pul-
verize the mass and extract it with boiling alcohol; filter
the solution while hot, the cholesterin being deposited on
cooling. If the crystals are colored, they may be redis-
solved and filtered through animal charcoal. This is the
proceeding employed by Poulletier de la Salle, Fourcroy
and Chevreul. It is only when this substance is mixed
with fatty matters that its isolation is a matter of any
difBculty. In extracting cholesterin from the blood I have
operated on both the serum and clot, and in this way have
been able to demonstrate it in greater quantities in this
fluid than have been observed by others, who have em-
ployed only the serum. The following is the process for
quantitative analysis, which I fixed upon after a number of
experihients.

The blood, bile or brain, as the case may be, is first
carefully weighed, then evaporated to dryness over a water-
bath, and carefully pulverized in an agate mortar, so as
to collect every particle. The powder is then treated
with ether, in the proportion of about a fluidounce for
every hundred grains of the original weight, for twelve
to twenty-four hours, agitating the mixture occasionally.
The ether is then separated by filtration, throwing a
little fresh ether on the filter so as to wash through every

NEW FUNCTION OF THE LIVER 175

trace of the fat, and the sohition is set aside to evap-
orate.* If the fluid, especially the blood, has been care-
fully dried and pulverized, when the ether is added it di-
vides it into a very fine powder and penetrates every part.
After the ether has evaporated, the residue is extracted
with boiling alcohol in the proportion of about a fluidrachm
for every hundred grains of the original weight of the speci-
men, filtered, while hot, into a watch-glass and allowed to
evaporate spontaneously. To keep the fluid hot while
filtering, the whole apparatus may be placed in the cham-
ber of "a large water-bath, or as the filtration is generally
rapid, the funnel may be warmed by plunging it into hot
water, or steaming it, taking care that it be carefully wiped.
We now have the cholesterin mixed with a certain quantity
of saponifiable fat. After the fluid has evaporated, we can
see the cholesterin crystallized in the watch-glass, mingled
with masses of fat. This we remove by saponification with
an alkali ; and for this purpose, we add a moderately strong
solution of caustic potash, which we allow to remain in
contact w'ith the residue for one to tw^o hours. If much
fat is present, it is best to subject the mixture to a tem-
perature a little below the boiling point; but in analyses
of the blood this is not necessary. The mixture is then
to be largely diluted with distilled water, thrown upon a
small filter, and thoroughly washed till the solution which
passes through is neutral. We then dry the filter, and fill
it up with ether, w'hich, in passing through, dissolves out
the cholesterin. The ether is then evaporated, the residue
extracted with boiling alcohol as before, the alcohol col-
lected on a watch-glass previously weighed, and allowed
to evaporate. The residue consists of pure cholesterin,
the quantity of W'hich may be estimated by weight.

The accuracy of this process may be tested by means of
the microscope. As the crystals have so distinctive a form
under the microscope, it is easy to determine by examining
the watch-glass that it has been obtained in a state of
purity. In making this analysis quantitatively it is nec-
essary to be very careful in all the manipulations; and for
determining the weight of such minute quantities, an accu-

* The ether may be preserved bv distillation, instead of allowintr it to evapo-
rate, but with the small quantity usually employed this is hardly worth while.

176 NEW FUNCTION OF THE LIVER

rate and delicate balance, one, at least, that will turn with
the thousandth of a gramme, carefully adjusted, must be
employed. With these precautions the quantity of cho-
lesterin in any fluid or solid may be determined with per-
fect accuracy. The quantity of cholesterin may be esti-
mated in fifteen or twenty grains of blood. In analyzing
the brain and bile I found it necessary to pass the
first ethereal solution through animal charcoal to get rid
of the coloring matter. In doing this the charcoal must
be washed with fresh ether till the solution which passes
through is brought up to the original quantity. The other
manipulations are the same as in examinations of the blood.
In examining the meconium I found that the cholesterin
which crystallized from the first alcoholic extract was so
pure that it was not necessary to subject it to the action
of an alkali.

I am aware that in describing the process for the ex-
traction of cholesterin I have entered into details which
would be superfluous for the practical chemist. But the
extraction of this substance from the blood is so simple,
and the results of the examination of blood in different
parts of the circulatory system have been so striking and
important, that I can not but indulge the hope that the
observations which follow will be verified by those who
may not be skilful practical chemists. Almost any one is
competent to make a quantitative analysis of the blood
for cholesterin. It simply requires six days for the process,
and a number of analyses may be carried on at the same
time. It requires one day, after the blood has been dried
and pulverized, for the ether to act upon it; the next morn-
ing it is filtered and set aside; the next morning it will be
dry and may be extracted with alcohol and set aside to
evaporate; the next morning it may be treated with pot-
ash, filtered, and the filter washed with water; the following
day it may be washed with ether and set aside to evapo-
rate; the following day it will have evaporated and may
be extracted with hot alcohol; and the following day the
alcohol will have evaporated and the specimen may be
examined by the microscope and weighed. All that is re-
quired is a little care in the performance of these simple
manipulations — which one with a slight acquaintance with
operations in chemistry may perform at once, and one or

NEW FUNCTION OF THE LIVER 177

two trials will enable a novice to execute — and accuracy
in weighing, which is, indeed, the most delicate part of
the process.

History of Cholesterin. — A brief sketch of the his-
tory of this substance may not be uninteresting. It was
first obtained by PouUetier de la Salle, in 1782, who ex-
tracted it from a biliary calculus. He communicated his
observations to Fourcroy, who pubHshed them, after hav-
ing verified his experiments, the death of the discoverer
preventing him from making his observations public.
Afterward, in examining an old hardened liver, Fourcroy
found a concrete oily substance analogous to that dis-
covered by PouUetier. He imagined that the liver had
become changed into a substance resembling spermaceti.
Cholesterin was afterward found in gall-stones, by Vicq
d'Azyr, Jaquin, Titius and Kreysig. In 1791 Fourcroy
described a substance which he called adipocire, found
in bodies at the Cimetiere des Innocents, which he likened
to spermaceti and to cholesterin. He always, however,
made a distinction between these substances; calling cho-
lesterin crystallizable adipocire. In 18 14 Chevreul estab-
lished the difference between adipocire and cholesterin,
giving a full description of the cholesterin. He extracted
it from the bile of the human subject, of the bear and of
the pig.

After that time a number of chemists found it in gall-
stones and in intestinal concretions. Lassaigne found it
in a cerebral tumor, Guerard in hydatid cysts of the liver,
Morin in the liquid from an abdominal tumor, Caventou
in the matter from an abscess under the malar bone, and
a number of others in tumors in various situations. In
1830 it was discovered in the blood by Denis, and after-
ward described by Boudet, who wrote an elaborate article
on the composition of the serum of the blood in 1833, in
which he described cholesterin and a new substance
which he called seroline.* It was also detected in normal
blood by Lecanu and Marchand. Couerbe, who made
elaborate researches into the chemical composition of the
cerebral substance, pointed out the existence of choles-

* Boudet, " Nouvelles recherches sur la composition du serum du sang
humain." — " Annales de chimie et de physique," tom. lii., p. 337.
12

178 NEW FUNCTION OF THE LIVER

terin in the brain. Lebert found it in the substance of
cancerous tumors, Curhng found it in the fluid of hydro-
cele, Simon extracted it from the meconium and Preuss
discovered it in the substance of crude tubercle. Of late
authors, Becquerel and Rodier have been most extended
in their investigation of this principle.* They have made
a number of careful quantitative analyses of the blood for
this substance in health and disease. Their observations
will be more particularly referred to farther on.f

Functions of Cholesterin. — By experiments which
I have performed upon the lower animals and by certain
facts which have been developed by observations on the
human blood in health and disease, I think I have been
enabled to solve the problem of the function of cholesterin.

Cholesterin is an excrementitious product, formed in
great part by the destructive assimilation of the brain and
nerves, separated from the blood by the liver, poured into
the upper part of the small intestine with the bile, trans-
formed in its passage down the alimentary canal into ster-
corin (the seroline of Boudet, a substance differing very
little from cholesterin), and, as stercorin, discharged by
the rectum.

The quotation with which I prefaced this paper ex-
presses the actual state of knowledge in regard to cho-
lesterin. Still, though our actual knowledge of its function
has been so slight, a few writers on chemical physiology
and on physiology, taking the limited data on this sub-
ject, make reference to it as an elTete substance. In
regard to its relation to the brain, some think that it is
formed in the brain and taken up by the blood, while others
think that it is formed in the blood and deposited in the
brain. All the views in regard to its efifete properties are
of course based on the supposition that it is discharged
in the feces. Effete matters are discharged from the body,
and this would find its exit by the anus, since it has never

* " Traite de chimie pathologique appliquee a la medecine pratique," par M.
Alf. Becquerel, Professeur agrege, etc., et par M. A. Rodier, Docteur en Mede-
cine, etc., Paris, 1854, and " Recherches sur la composition du sang," Paris,
1844.

f The history of cholesterin was compiled mainly from Robin and Verdeil,
the "Chimie anatomique."

NEW FUNXTIOX OF THE LIVER 179

been detected in the urine. These conjectures have at-
tracted little attention in the scientific world; and these
views being based on the supposition that this substance
is found in the fecal matters, fall to the ground from the
fact that no one as yet detected it in the feces. The fact
that cholesterin is so generally considered an ingredient
of the feces may be thus explained. It is poured into the
alimentary canal with the bile: no one has shown what
becomes of it, the chemistry of the feces being little under-
stood; and therefore it has been assumed that it is found
in the feces. That the facts which we have with regard
to cholesterin render its effete properties possible, and
perhaps probable, is certainly true; but these facts are
merely sufficient to enable the scientific investigator to
address an intelligent inquiry to Nature on this subject;
they do not solve the question. In the experiments
which form the basis of this article, the inquiry was made
and the answer obtained; some others have, without much
reflection apparently, made simple statements which ap-
proximate in some degree to the facts. The only way these
assertions could be sustained is by the labor which I have
expended in eliciting from Nature a reply to my interroga-
tories.

The works which I have had an opportunity of con-
sulting where any decided opinion relative to the function
of cholesterin has been expressed, are those of Carpenter,
Lehmann. ]\Iialhe and Dalton.*

Carpenter, in the fifth American edition of his " Human
Physiology," 1853, has the following in regard to the func-
tion of cholesterin:

" It is also stated to be a constituent of the nervous tissue,
having been extracted from the brain bv Couerbe. and other ex-
perimenters ; but it may be doubted whether this is not rather a
product of the disintegration of nerve-substance, which is destined
to be taken back into the blood for elimination by the excretory
apparatus, like the kreatine which may be extracted from the juice
of flesh, or the urea which is obtainable from the vitreous humor
of the eye, both being undoubtedly excrementitious matters. For
cholesterin is a characteristic component of the biliary excretion,
and is closely related to its peculiar acids: so'that it can scarcely
be looked upon in anv other light than as an excrementitious prod-

* These authors are quoted in the order in which their publications ap-
peared.

i8o NEW FUNCTION OF THE LIVER

uct, the highest function of which is to assist in the support of
the calorifying process. It is frequently separated from the blood
as a morbid product ; thus it is often present in considerable quan-
tity in dropsical fluids, and particularly in the contents of cysts;
and it may be deposited in the solid form in degenerated structures,
tubercular concretions, etc." *

In Lehmann, I find the following on this subject:

" Judging from the mode of its occurrence, we must regard it
as a product of decomposition ; but from what substances and by
what processes it is formed, it is impossible even to guess. Not-
withstanding the similarity which many of its physical properties
present to those of the fats, we can hardly suppose that it takes
its origin from them, since the fats, for the most part, become
oxidized in the animal body, whereas in order to form cholesterin,
they must undergo a process of deoxidation." f

I translate the following- from Mialhe, on " Chemistry
applied to Physiology and Therapeutics," Paris, 1856, the
paragraph entitled " Source of Cholesterine in the Animal
Economy."

" We have just examined in what manner the fatty bodies pene-
trate into the blood. Some eminent savans have held that the
fatty matters from the exterior are the only ones which exist in
the economy, and that it is incapable of producing these in itself.
Now it is an opposite opinion which tends to predominate, and the
majority of physiologists think that certain fatty bodies take origin
in the very substance of our organism. This last mode of origin
seems at least incontestable for the cholesterine, which has not yet
been found in the vegetable kingdom.

" But what are the chemico-physiological reactions which pre-
side over the development of this particular fatty substance?

" There are for us two modes for comprehending the formation
of the cholesterine at the expense of the elements of the blood.
Cholesterine may come from the fatty matters ; it would be. in this
case, like the final result or last stage of chemical modifications
which the fatty matters undergo in the animal economy.

"This manner of viewing it is slightly probable; for, in order
that it should be true, it would be necessary that the fatty bodies,
in oxidizing, should give rise to a compound richer than they in
carbon. We know, indeed, that cholesterine is, of all fatty bodies,
the one which contains the most carbon.

" We think that we should reject that opinion and stop at the
following:

" The production of cholesterine may be attributed to a trans-
formation of the albuminoid materials, a transformation analogous

* Carpenter, " Principles of Human Physiology," Philadelphia, 1853, p. 74,
+ " Physiological Chemistry," by Professor C. G. Lehmann, Philadelphia,
1855, vol. i., p. 24S.

NEW FUNCTION OF THE LIVER i8i

to that which has been pointed out by M. Blondeau de Carrolles
in cheese, and which that chemist has designated under the name
of adipose fermentation. The large proportion of carbon which
the cholesterine contains, and which approximates it to albuminous
matters, would come to the support of that point of view. The re-
tardation of the circulation, and the deficiency of oxidation which is
the consequence of it, explains also why the cholesterine is in much
greater proportion in the closed cavities than in the blood itself.

" Whichever it may be of these two opinions, it is incontestable
for us that, if the cholesterine is not burned with the other matters
proper to respiratory alimentation, it is solely on account of its
chemical inertia; cholesterine, indeed, is to fatty matters what
mannite is to saccharine substances — what urea is to albuminoid
matters; that is to say, that it constitutes a kind of caput mortuum,
of which the organism has only to free itself. It is certain also,
for us, that if the cholesterine is not found in all the excrementi-
tious liquids, where most of the other products existing in the
blood are found, it is solely on account of its insolubility.

" The preceding remarks explain perfectly, to our eyes at least,
why the presence of cholesterine has never been established in the
urine of man, either in the form of crystals, or * calculi,' while this
substance is found in the bile, where it very often forms calculi
of considerable size. Cholesterine, indeed, is insoluble in acid
liquids, such as the urine ; while it is soluble in soapy liquids, such
as the bile. Such is solely the reason why the cholesterine is ex-
creted by the biliary passages." *

Finally, in Dalton's " Treatise on Human Physiology,"
I find the following paragraph in which the subject of
cholesterin is considered:

"Cholesterine (C^^H.^O). — This is a crystallizable substance
which resembles the fats in many respects, since it is destitute of
nitrogen, readily inflammable, soluble in alcohol and ether, and en-
tirely insoluble in water. It is not saponifiable, however, by con-
tact with the alkalies, and is distinguished on this account from
the ordinary fatty substances. Tt occurs, in a crystalline form,
mixed with coloring matter, as an abundant ingredient in most
biliary calculi, and is found also in different regions of the body,
forming a part of various morbid deposits. We have met with it
in the fluid of hydrocele, and in the interior of many encysted
tumors. The crystals of cholesterine have the form of very thin,
colorless, transparent, rhomboidal plates, portions of which are
often cut out by lines of cleavage parallel to the sides of the crys-
tal. They frequently occur deposited in layers, in which the out-
lines of the subjacent crystals show very distinctly through the
substance of those which are placed above. Cholesterine is not
formed in the liver, but originates in the substance of the brain

*"Chimie appliqu^e a la physiologic et a la therapeutique," par M. le
Docteur Mialhe, p. igi. Paris, 1856.

i82 NEW FUNCTION OF THE LIVER

and nervous tissue, from which it may be extracted in large quan-
tity by the action of alcohol. From these tissues it is absorbed by
the blood, then conveyed to the liver, and discharged with the
bile." *

The above extracts embrace all that I have been able
to find bearing on the question of the function of choles-
terin. The extracts from Mialhe and Dalton contain all
that is said by them on this subject. Those from Carpen-
ter and Lehmann contain only what bears on the function
of this substance, the chemical details being omitted. Of
the authors cited, Mialhe is the most extended on the sub-
ject and is almost the only one who adduces any argu-
ments to support his views; but his opinions are biased
by the purely chemical view which he takes of the subject,
and are involved with the ideas with reference to plastic
and calorific food, now rejected by many eminent physiolo-
gists, and which, I conceive, will be so little supported by
future advances in science, that they wall soon be universal-
ly discarded, in the exclusive sense in which they are re-
ceived by him. Putting these hypotheses aside, examin-
ing the actual state of knowledge in regard to cholesterin,
it is seen that its function, up to this time, has not been
established. I shall now proceed to the facts which tend
to support the statement I have made on this point.

Cholesterin exists in the blood, from which it may be
■extracted in a state of purity and estimated by the pro-
cess which I have already indicated. Becqtierel and Ro-
■dier have made analyses of the healthy human blood for
this substance wdth the follow-ing results:

Venous blood of the male 0.09 pt. per i.ooo

" " " female 0.09 " " "

I have made a quantitative analysis of three specimens
of healthy human blood with the following results:

Quantity of blood. Cholesterin. Proportion
grains. grains. peri,ooopts.

Venous blood from the arm ; male £et. 35 312.083 0.139 0-445

" " " (colored) St. 22 187.843 0.123 0658

" " " ast. 24 102.680 0.077 0.751

* " A Treatise on Human Physiology," designed for the use of Students
and Practitioners of Medicine. By John C. Dalton, Jr., M. D., Professor of
Physiology and Microscopic Anatomy in the College of Physicians and Sur-
geons, New York, etc. Philadelphia, 1861, p. 189.

NEW FUNCTION OF THE LIVER 183

These three analyses were all carried on at the same
time, each specimen being subjected to precisely the same
process. The results show a wide range within the limits
of health. The difference was not due to any variation
relating to the digestive process, as the specimens were all
drawn at the same time, and were taken from prisoners
on Blackwell's Island, who were subjected to the same diet
.and ate at the same time. It will be seen by this table
that I have obtained five to eight times more than is
indicated by Becquerel and Rodier. I can explain this
only by the fact that I operated on the whole blood, while
they analyzed only the serum. Boudet states that it is
necessary to make three to four copious bleedings and
mix the serum in order to obtain a sufficient quantity for
a satisfactory analysis. I have operated on about fifty
grains of blood with success and have no doubt but that
I should be able to extract the cholesterin in a crystalline
form and estimate its quantity in fifteen or twenty grains.
The purity of the extract can easily be demonstrated
by a microscopic examination. I conclude, then, that
3. much larger quantity of cholesterin exists normally in
the blood than has been supposed, and that its varia-
tions in different persons, within the limits of health, are
•considerable.

The next question which naturally arises is the origin
of cholesterin. In examining the situations in which it is
found it is seen that it exists in largest quantity in the sub-
stance of the brain and nerves. It is also found in the sub-
stance of the liver, probably in the bile which is contained
in this organ, and in the crystalline lens, but with these
•exceptions it exists only in the nervous system and blood.
Two views present themselves in regard to its origin.
Cholesterin is deposited in the nervous matter from the
blood or is formed in the brain and taken up by the blood.
This is a question, however, which can be settled experi-
mentally, by analyzing the blood for cholesterin as it goes
to the brain by the carotid and as it comes from the brain
by the internal jugular. Cholesterin being found also in
the nerves, and, of course, a large quantity of nervous mat-
ter existing in the extremities, it is desirable at the same
time to make an analysis of the venous blood from the
general system.

i84 NEW FUNCTION OF THE LIVER

With reference to this question the following experi-
ment was made:

Experiment III. — A medium-sized dog, about six months old,
fasting, was put under the intiucnce of ether. The carotid and
internal jugular were exposed on the left side and the animal al-
lowed to come out from the effects of the anesthetic. Two hours
after, he was again etherized and blood was taken from the follow-
ing vessels in the order in which they are named: i, internal jugu-
lar; 2, carotid; 3, vena cava; 4, hepatic veins; 5, hepatic artery;
6, portal vein. In the operation of drawing the blood from the
abdominal vessels, immediately after opening the abdomen a liga-
ture was applied to the vena cava and a little blood taken, which
prevented the blood from the inferior extremities from mixing with
the hepatic blood. The blood was then taken from the hepatic
veins, a matter of some difificulty, as it is always more or less
mingled with blood returning through the thoracic vena cava, and
a ligature was applied to the hepatic artery and portal vein. The
blood was then drawn from the hepatic artery and portal vein.* A
quantity of bile was then taken from the gall-bladder, and a piece
taken from the substance of the brain. These specimens were
received into carefully weighed vessels and weighed ; but as I failed
to make a quantitative analysis, my process of extraction not having
been perfected, it is unnecessary to enter into their details. They
were then dried and pulverized, treated with ether, evaporated,
the residue extracted with hot alcohol, allowed to evaporate spon-
taneously, and examined with magnifying powers of 70, 270, and
400 diameters successively. The residue of the bile and brain were
found to consist of nearly pure cholesterin; but in all the other
specimens, except that from the internal jugular, the appearance
of cholesterin was doubtful. They all contained, with masses
of ordinary fat, crystals of stercorin.f There were a few distinct

* The operation of collecting the blood from any particular vessel is by no
means so easy as might at first be supposed. The greatest care is necessary in
order to obtain it unmixed. This is particularly so in the case of the hepatic
vein, the unmixed blood from which is exceedingly difficult to obtain. In draw-
ing blood, the operation must be done as rapidly as possible to avoid the de-
rangements of the circulation which arise from exposure of the vessels, pressure,
etc. In taking blood going to and coming from a part, it must always be taken
from the vein first ; as ligating or compressing the artery would of course arrest
the circulation. As the blood in the arterial system is not subject to the same
changes in composition as the blood in the different veins, any specimen of
arterial blood will represent the blood going to a part, unless, like the liver, it
receives blood from the venous system. The collection of blood I have found
the most difficult part of these investigations.

f Stercorin, or serolin, is a non-saponifiable fatty substance resembling
cholesterin in many of its chemical properties, but fusing at a much lower tem-
perature. It was discovered in the serum of the blood by Boudet about 1833.
It crystallizes in the form of needles, which will be more particularly described
when I treat of the extraction of this substance from the feces. As I have
found it in great abundance in the feces and am disposed to doubt its existence
as a natural constituent of the serum of the blood, I have called it stercorin,.
for reasons which will be more fully exposed farther on.

NEW FUNCTION OF THE LIVER 185

plates of cholesterin in the specimen from the internal jugular.
The specimens were then treated with a solution of caustic potash
and set aside. In two days part of the potash was removed with
bibulous paper and portions of the precipitates taken out, placed
upon slides, and examined microscopically with ^th and -xVth inch
objectives successively. The watch-glasses were then set aside,
carefully protected from dust, and examined again ten days after,
when they had become entirely dry. The following was the re-
sult of the examinations of the extracts of blood from the carot-
id, internal jugular, vena cava and the extract of. the brain. The
examination of the other specimens has nothing to do with the
question now under consideration, and their description is de-
ferred.

Blood from the Carotid Artery. — First examination, three
days after the operation, discovered a large number of small crys-
tals of stercorin and masses of fat ; but after the most careful ex-
amination, prolonged for two hours, I failed to discover any crys-
tals of cholesterin. The appearance is represented in Fig. 2.

The second examination, eleven days after, discovered a small
quantity of cholesterin mixed with the matters noted in the first
examination. This appearance is represented in Fig. 3.

Substance of the Brain. — All the microscopic examinations
of the extract from the brain showed crystals of cholesterin in
large quantity. The crystals from the brain are described by Robin
as being thinner and more elongated than those found in other
situations.* This peculiarity I also noticed. The appearance is
represented in Fig. 4.

Blood from the Internal Jugular. — In the first examination
of the specimen from the internal jugular, after the blood had
been treated with ether, the ether allowed to evaporate and the
residue extracted with hot alcohol, well-marked plates of choles-
terin were noted. At this time it could not be discovered in any
of the other specimens of blood after the most careful and patient
examination. After the caustic potash had been added, choles-
terin was demonstrated in large quantity, with a few crystals of
stercorin. The appearance is represented in Fig. 5, which was
drawn eleven days after the blood was collected. Another exam-
ination was made on the following day, which showed, in addition
to cholesterin, a considerable quantity of stercorin. (See Fig. 6.)

Blood from the Vena Cava. — The extract of the blood from
the vena cava, examined eleven days after the blood was drawn,
showed a large quantity of stercorin and a few crystals of choles-
terin. Cholesterin was distinct but not very abundant. (See
Fig- 7-)

These experiments, the first that I made on this sub-
ject, demonstrate the following^ facts: i. That the brain
contains a large quantity of cholesterin (which had, how-
ever, been previously established). 2. That the blood

* " Traite de chimie anatomique," Robin and Verdeil, tome iii., p. 57.

i86 NEW FUNCTION OF THE LIVER

going to the brain contains a small ([uantity of cholesterin,
while the blood coming from the brain contains a large
quantity. 3. That the blood coming from the lower ex-
tremities and i^elvic organs contains more cholesterin than
the blood carried to them by the arterial system.

It was only necessary to confirm these statements by
further investigation, to be enabled to deduce from them
the following important conclusions: That cholesterin is
formed in some of the tissues of the body; and, judging
from the fact that the nervous tissue is the only one in
which it is found and that the blood gains it in its passage
through the great nervous centre, it is formed in great
part by the nervous system. After the first experiment,
which almost confirmed the supposition with which I had
started, I directed my attention to the perfection of a pro-
cess by which I might make an accurate quantitative anal-
ysis of the blood for cholesterin, so as to be able to state
positively that it gained cholesterin in its passage through
certain organs, and furthermore to determine the amount
of increase. After a number of experiments I fixed upon
the process which I have minutely described in the first
part of this article, and made the following experiments
for the purpose of ascertaining the quantity of cholesterin
produced in the brain:

Experiment IV. — A medium-sized adult dog was put under
the influence of ether and the carotid artery, internal jugular and
femoral veins exposed. Specimens of blood were drawn, first from
the internal jugular, next from the carotid, and last, from the
femoral vein. These specimens were received into carefully
weighed vessels and weighed.

They were then analyzed for cholesterin by the process already
■described, and the following results obtained :

Quantity of blood. Cholesterin. Cholesterin per
grains. grains. i,ooo pts.

Carotid 1 79.462 o. 1 39 0.774

Internal jugular i34-78o 0.108 0.801

Femoral vein 133-886 0.108 0.806

Percentage of increase in blood from the jugular over the arte-
rial blood 3 488

Percentage of increase of blood from the femoral vein . . 4- 1 34

This experiment shows an increase in the quantity of
cholesterin in the blood during its passage through the
brain and an increase, even a little greater, in the blood

NEW FUNCTION OF THE LIVER 187

passing through the vessels of the posterior extremity.
To faciHtate the operation, however, the animal was
brought completely under the influence of ether, which,
from its action on the brain, would not improbably pro-
duce some temporary disturbance in the nutrition of that
organ and consequently interfere with the experiment. For
the purpose of avoiding this difiiculty I performed the fol-
lowing experiments without administering an anesthetic:

Experiment V. — A small young dog was secured to the oper-
ating table and the internal jugular and the carotid exposed on the
right side. Blood was taken, first from the jugular and afterward
from the carotid. The femoral vein on the same side was then
•exposed and a specimen of blood taken from that vessel. The ani-
mal was very quiet under the operation, though no anesthetic was
used, so that the blood was drawn without any difficulty and with-
out the slightest admixture.

The three specimens were analyzed for cholesterin with the
following results :

Quantity of blood Cholesterin. Cholesterin per
grains. grains. i,ooo pts.

Carotid 143.625 0.679 0.967

Internal jugular 29.956 0.046 1-545

Femoral vein 45-035 0.046 i .028

Percentage of increase in blood from the jugular over arterial

blood 59-772

Percentage of increase of blood from the femoral vein 6.308

Experiment VL — A large and powerful dog was secured to the
■operating table and the carotid and internal jugular exposed.
Specimens of blood were taken from these vessels, first from the
jugular, carefully weighed and analyzed for cholesterin in the
usual way. The following results were obtained :

Quantity of blood. Cholesterin. Proportion in
grains. grains. i,ooo pts.

Carotid 140.847 o. 108 0.768

Internal jugular 97-8 1 1 0.092 0.947

Percentage of increase in passing through the brain 23.307

Experiment V. shows a very considerable increase in
the quantity of cholesterin in the blood passing through the
brain, while it is comparatively slight in the blood of the
femoral vein. The proportion of cholesterin is also large
in the arterial blood as compared with other observations.

Experiment VI. shows but a slight difference in the
quantity of cholesterin in the arterial blood in the two ani-
mals; the proportion in the animal that was etherized being
0.774 pts. per 1,000, and in the animal that was not ether-

i88 NEW FUNCTION OF THE LIVER

ized 0.768 per 1,000, the difference being but 0.006; but,
as I had suspected, the ether had an influence on the quan-
tity of cholcsterin absorbed by the blood in its passage
through the brain. In the first instance the increase was
but 3.488 per cent., while in the latter it was 23.307. Un-
fortunately the blood was not taken from the femoral vein.
I intended to take blood from the abdominal organs, but
after opening the abdomen the struggles of the animal
were so violent that this was impossible, and he was killed.

What are the natural conclusions, from the preceding
experiments, in regard to the origin of cholesterin in
the economy? It has been found that the brain and nerves
contain a large quantity of this substance, which is found
in none other of the tissues of the body. The preceding
experiments, especially Experiments V. and VI., show that
the blood which comes from the brain contains a much
larger quantity of cholesterin than the blood which goes
to this organ.

The conclusion is, then, that cholesterin is produced in
the brain and thence absorbed by the blood.

But the brain is not the only part where cholesterin
is produced. It will be seen by Experiment IV. that there
is 4.134 per cent., and in Experiment V., 6.308 per cent,
of increase in cholesterin in the passage of the blood
through the inferior extremities, and probably about the
same in other parts of the muscular system. In examining
these tissues chemically, I find that the muscles contain
no cholesterin, but that it is abundant in the nerves; and
as it is found that the proportion of cholesterin is im-
mensely increased in the passage of the blood through
the great centre of the nervous system, taken, as the speci-
mens examined were, from the internal jugular, which
collects the blood from the brain and very little from the
muscular system, it is rendered almost certain, that in the
general venous system, the cholesterin which the blood
contains is produced in the substance of the nerves.

If this is true, and if, as I hope to show, cholesterin
is a product of the destructive assimilation of nervous
tissue, its production would be proportionate to the activ-
ity of the nutrition of the nerves; and anything which in-
terfered to any great extent with their nutrition would
diminish the quantity of cholesterin produced. In the

NEW FUNCTION OF THE LIVER 189

production of urea by the general system, which is an anal-
ogous process, muscular activity increases the quantity,
and inaction diminishes it, on account of the efifect upon
nutrition. In cases of paralysis there is a diminution of the
nutritive forces in the parts affected, especially of the nerv-
ous system, which, after a time, becomes so disorganized,
that although the cause of the paralysis be removed, the
nerves can not resume their functions. It is true that this
exists to a certain extent in the muscles; but it is by no
means so marked as it is in the nerves. We should be able,
then, to confirm the observations on animals by examining
the blood in cases of paralysis; when we should find a very
marked difference in the quantity of cholesterin between
the venous blood coming from the paralyzed parts and
that from other parts of the body. With this in view I
made analyses of the blood from both arms in three cases
of hemiplegia, which seemed to me most suitable for such
a comparison:

Case I. — Sarah Rumsby, jet. 47, affected with hemiplegia of
the left side. Two years ago she was taken with apoplexy and
was insensible for three days. When she recovered consciousness
she found herself paralyzed on the left side. Said she had epilepsy
four or five years before the attack of apoplexy. Now she has
entire paralysis of motion on the affected side, with the exception
of some slight power over the fingers, but sensation is perfect.
The speech is not affected. The general health is good.

Case II. — Anna Wilson, ?et. 23, Irish, affected with hemiplegia
■of the right side. Four months ago she was taken with apoplexy,
from which she recovered in one day with loss of motion and sensa-
tion on the right side. She is now improving and can use the
right arm slightly. The leg is not so much improved because she
wall make no effort to use it.

Case III.— Honora Sullivan, Irish, ret. 40, affected with hemi-
plegia of the right side. About six months ago she was taken with
apoplexy and recovered consciousness the next day, with paralysis.
The leg was less affected than the arm. from the first. The cause
was supposed by Dr. Flint, the attending physician, to be due to
an embolus. Her condition is now about the same as regards the
arm, but the leg has somewhat improved.

These cases all occurred at the Blackwell's Island Hos-
pital. The treatment in all consisted of good diet, frictions,
passive motion and use of the paralyzed members as much
as possible.

A small quantity of blood was drawn from both arms
in these three cases. It was drawn from the paralyzed

190

NEW FUNCTION OF THE LIVER

side, in each instance, with great difficulty, and but a small
quantity could be obtained.

The specimens were all examined for cholesterin, with
the following results:

Table of Quantity of Cholesterin in Blood of Paralyzed and
Sound Sides in Three Cases of Hemiplegia

Blood.

Cholesterin.

Cholesterin per 1,000.

Case I. Paralyzed side. . . .

grains.

55-458

grains.

The watch-glass contained
0.031 grain of a sub-
stance, but the most care-
ful examination failed to
show a single crystal of
cholesterin.

" Sound side

128.407

0.062

0.481.

Case II. Paralyzed side. . . .
" Sound side

18.381
66.396

0.062

Same as Case I.
0.808.

Case III. Paralyzed side

21.84a

Same as Case I.

" Sound side

52.261

0.031

0.579-

The result of these examinations is very interesting:
not a single crystal of cholesterin was found in any of the
three specimens of blood from the paralyzed side, while
about the normal quantity was found in the blood from
the sound side. As the nutrition of other tissues is inter-
fered with in paralysis, it is impossible to say positively,
from these observations alone, that cholesterin is produced
in the nervous system only. But the nutrition of the nerves
is undoubtedly most affected; and this observation, taken
in connection with the preceding experiments on animals,,
seems to settle where cholesterin is produced.

I may extend my first conclusion, then, and state that
cholesterin is produced in the substance of the nervous
system.

Before entering upon the character of cholesterin and
inquiring whether it is an excrementitious or recrementi-
tious product, I shall endeavor to follow it out in the sys-
tem and ascertain if there is any organ which separates
it from the blood. In pursuing this question, the method
will be adopted that has been employed in investigating-
its origin; that is. analyzing the blood as it goes to and
comes from certain organs. The organ which one would

NEW FUNCTION OF THE LIVER 191

be led first to examine is the liver, as it is the only gland
the product of which contains cholesterin, which, if not
manufactured in the gland itself, must be separated from
the blood.

In the first series of experiments which I performed on
this subject, I endeavored to show on the same animal
the origin of cholesterin in certain parts and its removal
from the body. In these experiments — in which the results
were approximative, as I had not succeeded in extract-
ing cholesterin perfectly pure — I began with the arterial
blood, examining it as it went into the brain by the carotid,
analyzing the substance of the brain; then analyzing the
blood as it came out of the brain by the internal jugular; ex-
amining the blood as it went into the liver by the hepatic
artery and portal vein; examining the secretion of the
liver; then the blood as it came out of the liver by the
hepatic vein; examining also the blood of the vena cava
in the abdomen. The analyses of the blood from the
carotid, internal jugular, and vena cava have already
been referred to, in treating of the origin of cholesterin.
It will be remembered that there was a large quantity of
this substance in the internal jugular, and but a small quan-
tity in the carotid, showing that it was formed in the brain.
I now give the conclusion of those observations, which
bears upon the separation of cholesterin from the blood.

Experiment VII. — Specimens of blood were taken from the
hepatic artery, portal vein and hepatic vein, and a small quantity
of bile from the gall-bladder. These specimens were treated in
the manner already indicated in Experiment III.; i. e.. evaporated
and pulverized, extracted with ether, the ether evaporated, and the
residue extracted with boiling alcohol, this evaporated, a solution
of caustic potash added and then subjected to a microscopic exam-
ination.

Blood from the Portal Vein. — Microscopic examination of
the extract from the portal vein showed quite a number of crystals
of cholesterin, which are represented in Fig. 8. These were ob-
served after the fluid had nearly evaporated.

Blood from the Hepatic Artery. — Microscopic examination
of the extract from the hepatic artery, made after the fluid had
nearly evaporated, showed a considerable quantity of cholesterin,
more than was observed in the preceding specimen. (See Fig. 9.)
There were also observed a few crystals of stercorin, represented
in Fig. 10.

Blood from the Hepatic Vein. — The first examination of the
extract from the hepatic vein, which was made just before the

192 NEW FUNCTION OF THE LIVER

potash was added, showed a number of fatty masses with some
crystals of stercorin. The solution of potash was then added, and
two (lays after, another careful examination was made, discovering
nothing but fatty globules and granules. (See Fig. ii.) The
watch-glass was then set aside and was examined eleven days
after, when the fluid had entirely evaporated. At this examination
a few crystals of cholesterin were observed for the first time. (See
Fig. 12.) There were also a number of crystals of margaric and
of stearic acid.

Bile. — All the examinations of the extract from the bile
showed cholesterin ; the precipitate consisted, indeed, of this sub-
stance in a nearly pure state. Fig. 13 represents some of the crys-
tals which were observed in this specimen.

Considering this series of experiments in connection
with the first observations on the carotid and internal jugu-
lar, while the one series demonstrates pretty conclusively
that cholesterin is formed in the brain, the other shows
that it disappears, in a measure, from the blood in its pas-
sage through the liver and is found in the bile. In other
words, it is formed in the nervous tissue and prevented
from accumulating in the blood by its excretion by the
liver. This suggests an interesting series of inquiries; and
this fact, if substantiated, would be as important to the pa-
thologist as to the physiologist. But in order to settle this
important question, it is necessary to do something more
than make an approximate estimate of the quantity of
cholesterin removed from the blood by the liver. The
cjuantity which is thus removed in the passage of the blood
through this organ should be estimated, if possible, as
closely as the quantity which the blood gains in its passage
through the brain. But this estimate is more difficult.
The operation for obtaining the blood, in the first place,
is much more serious than that for obtaining blood from
the carotid and internal jugular. It is very difficult to ob-
tain the unmixed blood from the hepatic vein; and the
exposure of the liver, if prolonged, must interfere with its
eliminative function, in the same way that exposure of the
kidneys arrests in a few moments the flow from the ureter.
It is probable, however, that the administration of ether
does not interfere with the elimination of cholesterin by
the liver as it does apparently with its formation in the
brain. Anesthetics have a peculiar and special action
on the brain, but they do not interfere with the functions
of vegetative life, like secretion or excretion; and there-

NEW FUNCTION OF THE LIVER

193

fore they would not interfere with the depurative function
of the Hver. It is fortunate that this is the case, for the
operation of taking blood from the abdominal vessels is
immensely increased in difficulty by the struggles of an
animal not under the influence of an anesthetic, so much
so, indeed, that I failed entirely in obtaining any blood
from one animal (the one used in Experiment VI.), which
was not etherized. It was a very powerful dog, and his
•struggles were so violent that it was impossible to collect
the blood accurately from the abdominal vessels and the
attempt was abandoned. With the view of settling the
question of the disappearance of a portion of the choles-
terin of the blood in its passage through the liver, by an
accurate quantitative analysis, I repeated the operation for
drawing blood from the vessels which go into and emerge
from the liver. In my first trial the blood was drawn so
unsatisfactorily and the operation was so prolonged, that
I did not think it worth while to complete the analysis and
abandoned the experiment. In the following one I was
more successful:

Experiment VIII. — A good-sized bitch (pregnant) was
brought completely under the influence of ether, the abdomen laid
freely open, and blood drawn first from the hepatic vein, and next
from the portal vein. The taking of the blood was entirely satis-
factory, the operation being done rapidly and the blood collected
without any admixture. A specimen of blood was then taken from
the carotid to represent the blood from the hepatic artery.

The three specimens of blood were then examined in the usual
way for cholesterin, with the following results :

Quantity of blood. Cholesterin. Cholesterin in
grains. grains. 1,000 pts.

Arterial blood 159-537 0200 1 — 57

Portal vein 168.257 0.170 1.009

Hepatic vein 79-848 0.077 0.964

Percentage of loss in arterial blood in its passage through the

liver 23.309

Percentage of loss in blood of the portal vein 4.460

This experiment proves positively what there was good
ground for supposing from Experiment VII.; namely, that
cholesterin is separated from the blood by the liver; and
here I may note, in passing, a striking coincidence be-
tween the analysis in Experiment VI., when the blood was
studied in its passage through the brain, and the one just
mentioned, when the blood was studied in its passage
13

194 NEW FUNCTION OF THE LIVER

through the H\'er. The gain of the arterial blood in cho-
lesterin in passing through the brain was 23.307 per cent.,
and the loss of this substance in passing through the liver
is 23.309 per cent. There must be, of course, the same
quantity sei)arated by the liver that was formed by the
nervous system, it being formed, indeed, only to be sepa-
rated by this organ, its formation being continuous, and
its removal necessarily the same, in order to prevent its
accumulation in the circulating fluid. The almost ex-
act coincidence between these two quantities, in speci-
mens taken from different animals, though not at all
necessary to prove the fact just mentioned, is still very
striking.

It is shown by Experiment VIII. that the portal blood,
as it goes into the liver, contains but a small percentage
of cholesterin over the blood of the hepatic vein, while
the percentage in the arterial blood is large. The arterial
blood is the mixed blood of the entire system; and as it
probably passes through no organ before it gets to the
liver, which diminishes its cholesterin, it contains a quantity
of this substance which must be removed. The portal
blood, coming from a limited part of the system, contains
less of this substance, though it gives up a certain quan-
tity. In the circulation in the liver, the portal system
largely predominates, and is necessary to other important
functions of this organ, such as the production of gly-
cogen. Soon after the portal vein enters the liver, its
blood becomes mixed with that from the hepatic artery,*
and from this mixture cholesterin is separated. It is only
necessary that blood, containing a certain quantity of cho-
lesterin, should come in contact with the bile-secreting"
cells, for this substance to be separated. The fact that
it is eliminated by the liver is proved with much less dififi-
culty than that it is formed in the nervous system. In
fact, its presence in the bile, the necessity for its constant
removal from the blood, which is consequent on its con-
stant formation and absorption by this fluid, are almost

* According to Robin, the branches of the hepatic arter}' are distributed
almost entirely in the interlobular plexuses and on the walls of the hepatic duct
and portal vein and do not find their way into the substance of the lobules. —
" Dictionnaire de medecine, de chirurgie, de pharmacie, des sciences acces-
soires et de I'art vdterinaire," P. H. Nysten ; " onzieme edition revue et cor-
rige." Par E. Littre et Ch. Robin. Paris, 1858. Article " Foie."

NEW FUNCTION OF THE LIVER 195

sufficient in themselves to warrant the conchision that it
is removed by the hver. This, however, is put beyond a
doubt by the preceding analysis of the blood going to and
coming from this organ.

Another link, then, is added to the chain of facts which
make up the history of cholesterin. The first is that —

Cholesterin is formed in the brain and nervous system
and is absorbed by the blood.

The second, which has just been proved, is that —

Cholesterin, formed in these situations and absorbed
by the blood, is separated from the blood in its passage
through the liver.

The next question, in following out this line of inquiry,
is, what becomes of the cholesterin which is separated from
the blood? This question is very easily answered, and
necessitates only an examination of one of the products
of the liver, the bile.

Bile. — In the few remarks with which I prefaced this
article, I spoke of the various opinions which are held
by physiologists with reference to the function of the
bile; some regarding it as purely excrementitious, others
placing it among the recrementitious fluids. I detailed
experiments which led me to think that it had two distinct
functions: one, which is recrementitious and is probably
concerned in digestion to an important degree, but which
it is not designed to take up in this connection; the other,
which is excrementitious, and which is necessarily taken
up in a discussion of the important substance now under
consideration. A glance at the composition of the bile
will show that it is an exceedingly complex fluid; and
physiological investigations into the destination of certain
of its ingredients, by Bidder and Schmidt, Dalton and
others, have shown that they are not discharged from the
body, but reabsorbed by the blood; though the failure to
detect them in the portal blood by the appropriate tests
shows that in this reabsorption they probably undergo some
alteration.* These substances, which have heretofore been
considered as the most important ingredients of the bile,

* For a very complete account of the bile, with original investigations into
the destination of the biliary salts, the reader is referred to an article published
by Prof. John C. Dalton, Jr., in the "American Journal of the Medical Sci-
ences," October, 1857, and the chapter on bile in Dalton's "Physiology."

196 NEW FUNCTION OF THE LIVER

though their function is obscure, are the glycocholate and
taurocholate of soda, discovered by Strecker in the bile of
the ox, in 1848. The following is the composition of the
bile given in Dalton's " Physiology," which is " based on
the calculations of Berzclius, Frerichs and Lehmann." *

Composition of Ox Bile

Water 880.00

Glycocholate of soda } go 00

Taurocholate of soda f ^'

Biliverdin 1

Fats ( J - . 2

Oleates, margarates and stearates of soda and potassa. . { -^'^

Cholesterin J

Chloride of sodium 1

Phosphate of soda |

Phosphate of lime [ 1 5.24

Phosphate of magnesia |

Carbonates of soda and potassa J

Mucus of the gall-bladder i .34

1 ,000.00

Of the above ingredients of the bile, are biliverdin,
which is simply a coloring matter; fats, with oleates, mar-
garates and stearates, which, with the biliary salts, are said
to hold the cholesterin in solution; chloride of sodium, pres-
ent in all the animal fluids; phosphates and carbonates,
which are simple excreted and are also ingredients of the
urine; leaving, as the most important constituents, of which
the function is least understood, the biliary salts and cho-
lesterin. The biliary salts are probably recrementitious;
but cholesterin is one of the products of the waste of the
system. The bile, then, presents the combined character,
so far as its chemical composition is concerned, of a secre-
tion and of an excretion. I may now contrast these two
properties and see what this fluid has in common with the
secretions and how it obeys the laws which regulate the
excretions. In doing this I shall first contrast some of the
important distinctions between these two classes of
products.

Secretions are characterized by certain constituents
which are formed in the substance of the gland and are
found in no other situation. Such is the pancreatin of
the pancreatic juice, the pepsin of the gastric juice, the

* Dalton's " Physiology," second edition, p. 158.

NEW FUNCTION OF THE LIVER 197

ptyalin of the saliva, and, I may add, the glycocholate and
the taurocholate of soda of the bile.

These substances first make their appearance in the
substance of the gland itself; they do not preexist in the
blood; they are discharged from the gland for a special
purpose, and when there is no necessity for their action,
the discharge does not take place. Illustrations of this are
to be found in the digestive fluids, which are true secre-
tions; poured out only when this function is called into
action by the ingestion of food, and not discharged from
the body, but their elements taken up again by the blood
when their function has been accomplished. Thus the gas-
tric and pancreatic fluids are never secreted until food is
taken into the alimentary canal, and are reabsorbed with
the digested matters.

The flow of the secretions is intermittent, and the gland,
during the period of repose, manufactures the elements of
the secretion, which are washed out at the duct when the
appropriate stimulus (of food, for example) causes a de-
termination of blood to the organ. The gland manufac-
tures the elements of the secretion, and the blood furnishes
the menstruum, the water, by means of which they are dis-
solved and emptied into the duct. When the pancreas of
an animal is exposed during the intervals of digestion, it
is pale and bloodless; no fluid flows from the duct; but
the elements of the pancreatic juice are, nevertheless, in
the gland; for they may be dissolved out from the gland,
and an artificial pancreatic juice results which will have
all the reactions and digestive properties of the natural
secretion. But if the pancreas of an animal is exposed
during digestion, the gland is turgid with blood; the secre-
tion flows from the duct, and the products of the gland
are being washed out by the blood — a process which is
imitated when they are dissolved out by maceration in
water. The late brilliant experiments of Bernard have
shown that the function of the glands is regulated by the
nervous system, and that faradization of certain nerves, by
which the nervous force is imitated, will cause a determi-
nation of blood to the organ and induce secretion, while
stimulation of other nerves will contract the vessels and
arrest secretion.

The substances which characterize the secretions, as

198 NEW FUNCTION OF THE LIVER

they are manufactured in the "lands and do not preexist
in the blood, do not accumulate in the blood when the
gland is removed or its functions are interfered with.

The distinctive characters of the secretions, in fact, may
be summed up thus:

Their elements first appear in the glands and do not
preexist in the blood. They are not discharged from the
body, with the exception of the milk, which is destined
for the nourishment of the child. Their flow is inter-
mittent. They are destined to assist in some of the nutri-
tive functions of the body.

Excretions, of which the urine may be taken as a type,
have entirely different characteristics:

Excrementitious substances do not first make their ap-
pearance in the organs which separate them, but are pro-
duced in the general system.

They preexist in the blood, having been absorbed by
this fluid from the parts of the system in which they are
formed, are carried to particular organs and are separated
from the blood for the sole purpose of being expelled from
the body. An illustration of this is to be found in urea,
which has been detected in the blood and urine and some
of the tissues of the body. This substance, one of the most
important excrementitious products, is absorbed by the
blood from certain parts of the system, carried to the kid-
neys, there separated from the blood and discharged from
the body. Although the gastric and pancreatic fluids, and
all the secretions proper, are reabsorbed with the food after
they have acted upon it, urea may remain any length of
time in the bladder, but it is never absorbed.

The flow of the excretions is constant. No period of
repose is necessary for the gland to manufacture their ele-
ments, as they all preexist in the blood. Nutrition is con-
stant, and destructive assimilation, or waste, which neces-
sitates nutrition or repair, is likewise constant. The blood
supplies all the wants of the system and receives all the
products of its decay. As the blood is continually being
impoverished, it must be regenerated from without; and
this is done by food, which is prepared for absorption by
digestion. The secreted fluids are chiefly concerned in
digestion; and as this is an occasional process, the secre-
tions are intermittent. But waste is continually going

NEW FUNCTION OF THE LIVER 199

on and excrementitious substances are continually form-
ing; and while the necessity for the secretions is occasional,
the necessity for the excretions is constant. Though the
actual discharge of the latter from the body is occasional,
they are constantly being separated from the blood, and
accumulate in receptacles, whence they are discharged at
appropriate intervals. No such receptacles exist for the
secretions proper, except in the instance of the milk, which
accumulates in the ducts of the mammary gland and is
the only secretion which is discharged from the body.

If the secreting glands take on an excretory function,
as is an occasional pathological occurrence, their flow be-
comes continuous. An example of this is the occasional
separation of urea from the blood by the gastric tubules.
When the kidneys become so affected by disease as to be
unable to separate the urea from the system, the accumu-
lation of this excretion in the blood frequently induces other
organs to attempt its removal. The gastric tubules take
on this function and produce a fluid which contains urea.
The gastric juice, if I may now so term it, is no longer
a secretion but an excretion; and its flow is no longer
intermittent and dependent upon the stimulus of food in-
troduced into the stomach, but is constant, and continues
until the irritation caused by the decomposing urea in the
stomach induces an inflammation which prevents further
secretion. This is an example of an intermittent secretion,
characterized by a substance manufactured in the gland
and not preexisting in the blood, changed into a constant
excretion, characterized by a substance which is not manu-
factured in the gland but preexists in the blood.

The substances which characterize the excretions accu-
mulate in the blood when the organ which eliminates them
is removed or its functions are interfered with. It is this
fact which led to a knowledge that urea preexisted in the
blood. It was detected in that fluid when it had accumu-
lated in animals from which the kidneys had been removed,
and in cases of Bright's disease of the kidneys, before
chemical processes were sufficiently delicate to detect it
in healthy blood, when the quantity is kept down by its
constant elimination by the kidneys.

The characters of the excretions, then, are entirely op-
posite to those of the secretions.

200 NEW FUNCTION OF THE LIVER

Their elements preexist in the blood and are not manu-
factured in the substance of the organs which eliminate
them. Their flow is constant. They are separated from
the blood merely to be discharged from the body and are
not destined to assist in any of the nutritive functions.

Having contrasted the secretions and the excretions,.
I shall now examine the bile and note what are the char-
acters which it has in common with either or both of these
products.

The bile is characterized by two kinds of constituents:
One of them, the glycocholate and the taurocholate of
soda, manufactured in the liver, found in no other fluid than
the bile, does not preexist in the blood, and associates the
bile with the secretions. The other, the cholesterin, pre-
exists in the blood and is simply separated from it by the
liver, giving the bile one of the characters of an excretion.

The biliary salts (the glycocholate and taurocholate
of soda) are discharged into the intestinal canal for a spe-
cial purpose; and this discharge takes place at the begin-
ning of the digestive act. If the liver and gall-bladder
of a dog which has not taken food is exposed, the gall-
bladder will be found distended with bile; but if these or-
gans are examined when digestion is going on, the gall-
bladder will be found nearly empty. It is true that after
prolonged fasting the bile is discharged into the alimen-
tary canal, but it must be remembered that it contains
another ingredient, cholesterin, which must be discharged
from the body, as will appear presently. The biliary salts
are not discharged from the body. Dr. Dalton has shown
that the substances extracted from the contents of the
large intestine by evaporation, extraction of the residue
with alcohol and precipitation with ether, will not react
with Pettenkofer's test, which is a very delicate test for
the biliary salts. I have treated the feces of the human
subject in the same way with the same result. These salts,
therefore, are not discharged from the body unchanged.
The next question to determine is whether they are dis-
charged from the body in a modified form. They contain
a certain quantity of sulphur, of which, as has been shown
by Bidder and Schmidt, only one-fifteenth part of the en-
tire quantity which enters the intestine with the bile can
be detected in the feces. As sulphur is an elementary sub-

NEW FUNCTION OF THE LIVER 201

stance, it can not be decomposed; and the biliary salts, in
their passage down the alimentary canal, mnst be absorbed.
It is true that these salts can not be detected in the blood
coming from the intestines, but we can not detect the pan-
creatin of the pancreatic juice, the pepsin or the acid
of the gastric juice in the portal blood, yet these are ab-
sorbed by the mucous membrane of the intestinal tube,
changed by their union with the matters they have di-
gested. It is probable that an analogous change takes
place in the glycocholate and taurocholate of soda, which
prevents them from being detected in the blood by the
ordinary tests. These facts, also, place the bile among the
secretions.

On the other hand, cholesterin preexists in the blood,
having been absorbed by this fluid from certain parts of
the system, is carried to the liver and there separated for
the sole purpose of being discharged from the body. The
same general remarks apply to this substance as to urea.
This places the bile among the excretions.

The flow of the secretions is intermittent. This is not
absolutely true of the bile, but the discharge of this fluid
is remittent. Dr. Dalton * has reported a series of inter-
esting experiments upon an animal with a duodenal fistula.
In this observation ten grains of dry biliary matter were
discharged into the duodenum of a dog w^eighing thirty-
six and a half pounds, immediately after feeding. At the
end of the first hour it had fallen to four grains; it con-
tinued at three and a half to four and a half grains up to
the eighteenth hour, when the quantity was inappreciable;
at the twenty-first hour it was one grain; the twenty-fourth,
three and a quarter grains; and the twenty-fifth, three
grains. The fluid was drawn for fifteen minutes each time,
evaporated to dryness, extracted with absolute alcohol,
precipitated with ether, the ether precipitate dried and
weighed as representing the quantity of biliary matter
present. These experiments apply to the time when the
bile is discharged into the intestine; but as most animals
have a gall-bladder, which collects the bile as it is secreted,
it does not show when this fluid is formed by the liver.
Schwann, Bidder and Schmidt, Arnold, Kolliker and Miil-

* Dalton, " Constitution and Physiology of the Bile." Loc. cit.

NEW FUNCTION OF THE LIVER

ler, have made experiments bearing;- upon the latter point,
bv ligating- the ductus communis choledochus and making
a fistula into the fundus of the gall-bladder. The experi-
ments of these observers vary somewhat in regard to
the time when the secretion of the bile is at its maximum.
In the animal already referred to, in which a fistula was
made into the fundus of the gall-bladder, the bile was
collected for thirty minutes immediately after feeding, one
hour after, and then at intervals of two hours during the
remainder of the twenty-four hours. The specimens of bile
thus collected were carefully weighed, evaporated to dry-
ness and the proportion of dry residue taken. The fol-
lowing table shows the results of these observations, which
were made twelve days after the operation, when the ani-
mal, which weighed originally twelve pounds, had lost two
pounds. His appetite was ravenous at the time of the
experiment.

Table of the Variations of the Bile in the Twenty-four
Hours. At each observation the bile was drawn for precisely thirty
minutes. Dog with a fistula into the gall-bladder. Weight ten
pounds.

Time after Feeding.

Immediately

One hour

Two hours

Four hours

Six hours

Eight hours

Ten hours

Twelve hours

Fourteen hours. . . .

Sixteen hours

Eighteen hours. . . .

Twenty hours

Twenty-two hours.
Twenty-four hours

Fresh bile.

Dried bile.

Percentage of
dry residue.

grains.

grains.

8.103

0.370

4.566

20.527

0.586

2

854

35 • 760

1.080

3

023

38.939

1.404

3

605

22 . 209

0.987

4

450

36.577

1.327

3

628

24.447

O.S33

3

407

5.710

6.247

4

325

5.000

0.170

3

400

8.643

0.309

3

575

9.970

0.277

2

778

4 769

0.170

3

565

7.578

0.293

3

866

15.001

0.885

5

233

This table shows a regular increase in the quantity of
bile discharged from the fistula from the time of feeding
up to four hours after. It diminished at the sixth hour,
rose again at the eighth hour, but then gradually dimin-
ished to the fourteenth hour. There was then a slight
increase the sixteenth and eighteenth hours, and the twen-

NEW FUNCTION OF THE LIVER 203

tieth hour it fell to its minimum. It then increased slight-
ly the twenty-second hour, and mounted considerably the
twenty-fourth hour, when the observations were concluded.
Disregarding slight variations in the quantity, which might
be accidental, it may be stated in general terms that the
maximum flow of bile from the liver is from the second
to the eighth hour after feeding, during which time it is
about stationary. In this experiment it was at its mini-
mum the twentieth hour after feeding. This observation
agrees with those of Bidder and Schmidt as regards the
time when the bile begins to increase in quantity; but these
observers state that it is at its maximum from the twelfth
to the fifteenth hour. This, however, is not material to
the question now under consideration. I wished to estab-
lish the fact that the quantity of bile secreted varied con-
siderably during the various stages of the digestive act; a
character which approximates it to other secretions. The
flow' of the bile is not intermittent, because it contains a
substance which is excrementitious; but it is remittent,
having a definite relation to the digestive act, because it
■contains substances which are recrementitious and are in
some way connected with the process of digestion.

The continuous though remittent flow of the bile al-
lies it with the excretions. There is no time, in health,
when the bile is not separated from the blood. In animals
that go through the process of hibernation, the bile con-
tinues to be secreted, though no food is taken into the
alimentary canal. Nutrition, though much diminished in
activity, goes on during this state, and the urea and cho-
lesterin must be separated from the blood. The formation
of the bile and urine, therefore, is not interrupted. Bile is
secreted also in the foetus, before any nourishment is taken
into the alimentary canal, when none of the other digestive
fluids are formed. This character it has in common with
the urine, and this places it among the excretions.

The elements of secretion never accumulate in the sys-
tem when the secretion is interfered with; while the ele-
ments of excretion do accumulate in the blood in such
cases and produce certain toxic effects. Experimenters
have often analyzed the blood for the biliary salts in cases
of serious disease of the liver, marked by symptoms of bile-
poisoning, regarding these as the only important elements

204 NEW FUNCTION OF THE LIVER

of the bile; but they have never been detected. I have
made no observations on this point, for the fact that the
glycocholate and taurocholate of soda do not accumulate
in the blood in diseases of the liver has long been set-
tled. This stamps these substances as products of secre-
tion; l)ut we shall see when some of the pathological con-
ditions of the cholesterin are taken up, that this substance
does accumulate in the blood when the functions of the
liver are seriously interfered with, which marks it as a
product of excretion.

It seems to me that enough has been said in regard
to the function of the bile to convince the reader that
this complex fluid has two important ingredients which
have two separate functions.

First. — It contains the glycocholate and taurocholate
of soda, which are not found in the blood, are manufac-
tured in the liver, are discharged mainly at a certain stage
of the digestive process, are destined to assist in some of
the nutritive processes, are not discharged from the body
and, in fine, are products of secretion.

Second. — It contains cholesterin, which is found in the
blood, is merely separated from it by the liver and not
manufactured in this organ, is not destined to assist in any
of the nutritive processes but is merely separated to be
discharged from the body, and is a product of excretion.

These two propositions, especially the second, being
established, it becomes necessary now to follow out choles-
terin after it has been discharged from the liver into the
small intestine. If it is discharged from the body it must
be by the rectum ; and to complete the history of cholesterin
it becomes necessary to study the feces.

Feces. — It is not my object to consider all the effete
matters which go to make up the feces, although it must
be acknowledged that information on this subject is very
limited. Following cholesterin in its passage down the
alimentary canal has opened a new subject for investiga-
tion, to which it will be impossible to do entire justice
in this paper. There is a field for a long series of investiga-
tions into this part of our subject, which I hope to be able
to cultivate to some extent in the future and to add some-
thing to the history of the substance I have been con-
sidering. At present I shall endeavor only to demon-

NEW FUNCTION OF THE LIVER 205

strate the fact that cholesterin, in a modified form, is dis-
charged with the feces, and not attempt to treat of the
conditions which modify the excretion of this snl^stance
(upon which as yet I have no data), which are of great
importance to the practical physician.

It is stated by some of the most rehable authors on
physiology and physiological chemistry that cholesterin is
found in the fecal matters. Robin and Verdeil say, " Ce
principe immediat se trouve a I'etat normal dans le sang,
la bile, le foie, le cerveau, les nerfs, le crystallin et les ma-
tieres fecales." Many other authors refer to it as found
in the feces, and it was with that belief, that, in the ex-
periments which form the basis of this article, I deferred
my analyses of the feces till I had completed the observa-
tions on the blood, and then analyzed them, satisfied that
I should find cholesterin, with the view to determine the
variations, etc., in its quantity. When, after a careful and
prolonged examination of many specimens of feces, I was
unable to extract any cholesterin, I endeavored to ascer-
tain what observer had established its presence. Though it
is mentioned by so many as present in fecal matter, I could
iind no mention of any one who had established this point;
and in some of the analyses of Simon. I found that he had
noted its absence in certain specimens of feces. I found
also that Marcet, who published some elaborate analyses
of the feces in the " Philosophical Transactions," in 1854
and 1857, noted the absence of cholesterin in the normal
feces of the human subject. It has already been seen how
conclusively the experiments on the blood from various
parts of the system point to the excrementitious character
of cholesterin, showing, even, in what part of the sys-
tem it is found and where it is eliminated; but it is un-
doubtedly one of the most important characters of an ex-
cretion that it should be discharged from the body, and
I was unable for a time to convince myself that it was dis-
charged. After evaporating the feces to dryness, pulver-
izing, extracting thoroughly with ether, decolorizing with
animal charcoal, evaporating the ether and extracting the
residue with boihng alcohol, I allowed the alcohol to evap-
orate, added a solution of caustic potash, and kept the
mixture at a temperature near the boiling point for three
and a quarter hours. The potash was then carefully

2o6 NEW FUNCTION OF THE LIVER

washed away on a filter, the residue rechssolved in ether
and extracted with hot alcohol as before, and the alcoholic-
extract set aside to evaporate. A number of days passed
without any sign of crystallization. The residue was, of
course, non-saponifiable; but it differed from cholesterin
by being melted at a much lower temperature, though it
presented the red color with sulphuric acid which is said
to be characteristic of the latter substance. It w^as exam-
ined carefully with the microscope daily; and after five
or six days, to my great satisfaction, crystals began to
appear; but they were at first so indistinct that their form
could not be clearly made out. These crystals, however,
increased in size and number, and in a short time pre-
sented the characteristics of serolin. In about ten days the
whole mass had crystallized, making one of the most su-
perb exhibitions of crystals that could be imagined. Sero-
lin crystallizes in the form of delicate transparent needles,
which have a beauty under the microscope which could be
but poorly imitated by the most delicate steel plate en-
graving. This substance, from its being found in such large
quantity in the feces, I have spoken of as stercorin.

Before taking up the changes which cholesterin under-
goes in its passage down the alimentary canal, I shall say
a few words in regard to stercorin.

STERCORIN

Stercorin has already been referred to and delineated
in the analyses of various specimens of blood for choles-
terin. It was observed by Boudet and described by him
under the name of seroline, in an article published in the
" Annales de chimie et de physique," in 1833, as a prin-
ciple found in the serum of the blood. Up to the present
time, this is the only situation in w^hich it has been found,
and here in such an excessively minute quantity that
enough has never been obtained for ultimate chemical
analysis. In regard to its function nothing whatever
has been known. Robin thus speaks of it: " On ne sait
pas comment se forme la seroline, ni quel est son role
physiologique." *

* Robin and Verdeil, " Chimie anatomique et physiologique," tome iii.^
p. 66.

NEW FUNCTION OF THE LIVER 207

Chemical Characters. — This substance, like choles-
terin, is a non-saponifiable fat. It has never been obtained
in sufficient quantity for ultimate chemical analysis; but as
in its decomposition it disengages a little ammonia, it is
supposed by Verdeil and Marcet to contain nitrogen.*
The evidences of this ingredient are very slight, and its
existence is doubtful. It is neutral, inodorous, insoluble
in water, soluble in ether, very soluble in hot alcohol but
almost insoluble in cold. It is not attacked by the caustic
alkalies, even after prolonged boiling-. When treated with
strong sulphuric acid it strikes a red color similar to
that produced by sulphuric acid and cholesterin. Ac-
cording to Lehmann it melts at 96.8° Fahr., and on the
application of strong heat may be distilled without change.
Boudet extracted it from the serum of the blood by evap-
orating, boiling the residue with water and evaporating
again, taking up the residue with boiling alcohol, which
deposited the crystals on cooling.

Form of its Crystals. — Boudet describes the crystals
thus obtained as filaments, with varicosities here and there
which gave them a beaded appearance. Lecanu also ob-
served this peculiarity. In the atlas of Robin and Verdeil's
" Chimie anatomique " there is a beautiful representation
of the crystals of serolin from the blood. These observ-
ers have not noticed the beaded appearance mentioned
by Boudet, but represent the crystals in the form of deli-
cate transparent needles, of variable size, some very small
and others quite wide, terminating in fine pointed extrem-
ities, which in some of the wider crystals is bifurcated
or even trifurcated, with the edges of the larger crystals
frequently split, as it were, into delicate filaments. The
smaller crystals frequently arrange themselves in a fan-
shape. Robin and Verdeil attribute the beaded appear-
ance mentioned by Boudet and Lecanu to the presence
of little globules of fatty matter mixed with the crystals.
This seems probable, for it will be seen in examining the
process of extraction employed by Boudet, that he prob-
ably did not succeed in obtaining it in a pure form. The
appearance of these crystals has already been given in some
of the diagrams of cholesterin, especially in Figs. 2, 6, 7,

* " Cours de physiologic fait a la Faculte de Medecine de Paris." Par P.
Berard, Professeur de Physiologic, etc. Paris, 1851, tome iii., p. 118.

2o8 NEW FUNCTION OF THE LIVER

and 9. I have been able to follow the process of crystal-
lization in the specimens extracted from the feces from
its beginning, and have found that the splitting of the
ends and edges of the crystals did not take place at first.
The needles which were first formed had regular borders
and single pointed extremities; but after a few days they
split up in the manner described and figured by Robin and
Verdeil. (See Figs. 14 and 15.)

Situations. — Up to this time, serolin (or stercorin)
has been found only in the serum of the blood, and there
in but very small quantity, the proportion being, according
to the analyses of Becquerel and Rodier, 0.020 to 0.025
of a part per 1,000 parts of blood. They have seen it mount
up to 0.060 parts, and descend to a quantity almost in-
appreciable.*

Process of Extraction. — In the first observations I
made on the blood this substance was observed before
cholesterin. In these observations the blood was dried,
pulverized, extracted with ether, the ether evaporated, the
residue extracted with boiling alcohol and then a solution
of caustic potash added which remained on the specimens
for a number of days. In all the subsequent analyses of
the blood cholesterin was extracted perfectly pure, and no
stercorin whatever was observed. The following was the
difference in the modes of analysis. In the latter case
the solution of potash was not allowed to remain on the
specimens more than an hour or two; but was washed
aw^ay, and the residue which was left on the filter was redis-
solved in ether. The failure to detect the stercorin in all
the later observations on the blood, which are twenty-four
in number, inclines me to the opinion that it does not pri-
marily exist in this fluid; and that when it has appeared
in the extract it has been due to a transformation of a
portion of the cholesterin. This view seems the more prob-
able as I have definitely ascertained by observations on
the feces, which will be detailed farther on, that cholesterin
is capable of being changed into stercorin, and that this
change actually takes place before it is discharged from
the body. In my observations on the blood no attempt
was made to get rid of this substance; and though it is

* " Traite de chimie pathologique appliqude k la medecine pratique." Par
MM. Alf. Becquerel and A. Rodier. Paris, 1854, p. 62.

NEW FUNCTION OF THE LIVER 209

soluble in the menstrua which were used to extract cho-
lesterin and is not destroyed by any of the means that
were employed to purify the cholesterin, it never appeared
in the extract. In these experiments the study of ster-
corin in the blood has not been attempted; and though it
is not possible to state at present how the cholesterin was
transformed in the first observations, it seems most rational
to suppose, in endeavoring to explain its absence in the
twenty-four succeeding specimens of blood which were ex-
amined, that such a change had taken place.

I am inclined to the opinion, then, though I can not
state it positively, that the substance under consideration
•does not exist in the blood as a proximate principle, but
is formed from cholesterin, in some unexplained way, by
the processes which have been used for its extraction.*
This transformation does not take place during the ex-
traction of this substance from the feces, because I have
in but a single instance been able to extract cholesterin by
the processes which are successful in obtaining it in other
situations in which it exists, including meconium.

Stercorin may be extracted from the feces in the fol-
lowing way: The feces are evaporated to dryness, pulver-
ized and treated with ether, which should be allowed to
remain for twelve to twenty-four hours, protected from
evaporation. The ether is then separated and decolorized
by filtration through animal charcoal, fresh ether being
added till the original quantity has passed through. It is
impossible to decolorize the solution entirely, but it should
be made to pass through of a very pale amber tinge and
perfectly clear. The ether is then evaporated and the resi-
due extracted with boiling alcohol. The alcohol is then
evaporated and the residue treated with a solution of caus-
tic potash, at a temperature a little below the boiling point,
for one or two hours. This dissolves all the saponifiable
fats, and the solution is then largely diluted with water,
thrown on a filter and washed till the fluid which passes
through it is perfectly clear and neutral. The filter is then
dried at a moderate temperature and the residue washed

* In the absence of an ultimate analysis of this substance, it is impossible
to enter into any chemical speculations in regard to the change from choles-
terin, as in the instance of creatin and creatinin or urea and carbonate of am-
monia.

14

2IO NEW FUNCTION OF THE LIVER

out with ether, which is evaporated, extracted with boiling
alcohol and evaporated again. The residue is composed
of pure stercorin.* The extract thus obtained is a clear,
slightly amber, oily substance, of about the consistence of
the ordinary Canada balsam used in microscopic prepara-
tions, and in four or five days begins to show the charac-
teristic crystals. These are at first few in number; but soon
the entire mass assumes a crystalline form. In a specimen
which I extracted from the feces I have 10.417 grains,
consisting, apparently, of nothing but crystals. If the ex-
tract *is evaporated in a very thin watch-glass it may be
examined with the microscope daily and the process of
the formation of the crystals observed. These crystals,
after they are fully formed, may be examined satisfactorily
with a half or quarter-inch objective.

History of Serolin. — Very little is to be said in
regard to the history of this substance. Boudet first de-
scribed it in i833.f Lecanu confirmed these observations
in 1837.:!: Since then it has been studied by Becquerel and
Rodier," Chatin and Sandras,|| W. Marcet and Verdeil."^
Gobley states, in an article published in the " Journal de
chimie medicale," that the substance described by Boudet
is not an immediate principle but a mixture of several sub-
stances, confounding it, how^ever, with cholesterin.O Ro-
bin and Verdeil adopt this view, but consider it entirely
different from cholesterin.l

This substance, existing, as it does, in large quantities.
in the fecal matter, must take its place among the im-
portant excrementitious matters discharged from the or-
ganism, not second in importance, even, to urea. It is
a curious fact that while urea was known as an ingredi-
ent of the urine long before it could be demonstrated

* As this substance is said to be volatilized at a high temperature, it is im-
portant to avoid as much as possible the application of heat. Large quantities
of it are extracted from the feces after evaporation over an ordinary water bath,
but it might be better to evaporate the excrements at a lower temperature.

\ Boudet. Loc. cit.

X Lecanu. " Etudes chim. sur le sang humain, these." Paris, 1837, p. 55.

* Becquerel and Rodier. " Recherches relatives a la comp. du sang."
(" Comptes Rendus." Paris, 144, tome xix., p. 1084.)

II Chatin et Sandras. " Gaz. des hopit.," 1849, p. 289.
'^ Berard. Loc. cit.

0 Gobley. "Sur les matieres grasses du sang." ("Journal de chimie
medicale," 185 1. Paris, p. 577.)
% Robin et Verdeil. Loc. cit.

NEW FUNCTION OF THE LIVER 211

in the blood, taking its name from that fluid, stercorin, an
excrement of great importance, was discovered in the blood
and never till now has been recognized as an excrement
and an ingredient of the feces, taking a name from the
serum of the blood, which does not indicate at all its ex-
crementitious properties or the situation in which it is
found in g^reatest abundance. As seroHn has been here-
tofore a substance of very little prominence, and as it
probably does not exist normally in the serum of the blood,
and if at all, in insignificant quantity, the appellation seems
a misnomer. It should be known by a name which will
indicate its excrementitious properties and the channel by
which it is evacuated; and I have adopted the name Ster-
corin * as more appropriate and more suggestive of its
properties, as it is undoubtedly the most important ex-
crement discharged by the anus.

The questions which now arise in regard to this sub-
stance open a field of inquiry too extensive, by far, to be
thoroughly investigated in the time that could be devoted
to this subject, or to be discussed within the limits of this
paper. It would be desirable to know the full history
of this product, the quantity discharged in twenty-four
hours, variations that may take place with season, age, sex,
diet, digestion, etc., and especially the modifications which
occur in its discharge in connection with diseased condi-
tions. These points are of great importance; but they
require a long and laborious series of investigations for
their elucidation. What has been done in a measure for
urea must be done for stercorin, before arriving at a
precise idea of its relations to disease. For this pur-
pose a large number of quantitative analyses of healthy
feces must be made and compared with similar analyses
in different diseases. At present I have instituted only a
sufficient number of examinations to substantiate the
statements I have made in regard to the formation and
discharge of this substance, and have added a few exam-
inations of feces in disease which bear upon the same
points. I hope at some future time to go more fully into
the study of the feces and to contribute something toward
the elucidation of some of the questions which naturally

* From Stercus, 6ris, dung.

212 NEW FUNCTION OF THE LIVER

arise. In the mean time I present the following observa-
tions on stercorin as it appears in the feces:

Experiment IX. — Seven and a half ounces of feces, perfectly-
normal in appearance and being the entire quantity passed in the
morning at the regular time for an evacuation, were taken from
a healthy male, twenty-six years of age. After being evaporated
and finely pulverized in an agate mortar, the residue weighed 2 oz.
57.313 grains. A small quantity was then extracted with alcohol,
the solution being of a yellow color, and about six times its vol-
ume of ether added. The ether was filtered after standing for
fifteen minutes, the filter washed with distilled water, and the solu-
tion tested with Pettenkofer's test for the biliary salts. None of
these salts were present.

A watery solution was then made of another portion, which
was filtered and tested with nitric acid, but failed to show the reac-
tions of the coloring matter of the bile.

The dry residue was then treated with five fluidounces of ether
for twenty hours, when it was filtered through animal charcoal,
fresh ether being added till the fluid which passed through made
five ounces. It came through perfectly clear and of a very light
golden tinge. It was then evaporated, leaving a golden yellow fat
with a number of whitish resinous masses. It was then extracted
with ojss of boiling alcohol, which removed everything but a small
quantity of bright yellow oil, and filtered while hot. It became
turbid on cooling and was set aside to evaporate. Both the ethereal
and alcoholic extracts had a very offensive rancid odor. The
residue, after the evaporation of the alcohol, consisted of a con-
siderable quantity of fat of a yellowish color and of a consistence
like thick turpentine. It was then treated with a solution of caustic
potash, kept near 212° for about thirty minutes and allowed to
stand for twenty hours. At the end of that time a large quantity
of fat floated on the top of the fluid not at all affected by the al-
kali. It was then largely diluted with distilled water filtered and
washed, the filter dried, and the residue redissolved in ether. This
ethereal solution was evaporated and the residue extracted with
boiling alcohol as before. After the alcohol had evaporated, a
small quantity was treated with sulphuric acid which produced a
peculiar red color similar to that produced when the acid was
added to a specimen of cholesterin, extracted from the blood and
used for purposes of comparison.

Five days after, the specimen was examined with a T*oth inch
objective and presented some crystals which looked like serolin ;
but it was impossible, on account of the thickness of the glass cap-
sule, to apply a sufficiently high power to make this certain. Some
long, pale, radiating crystals were observed, composition unknown,
"but they were not the crystals of excretin described by Marcet.*

* Marcet, in two papers published in the " Philosophical Transactions" for
1S54 and 1857, describes a new proximate principle in the feces which he calls
Excretin. This he obtains in the following way : He first treats the feces

NEW FUNCTION OF THE LIVER 213

The specimen was treated again with a solution of caustic potash
and kept at nearly the boiling point of water for three and a quarter
hours, most of the fat floating on the top of the fluid in white flakes
and yellow drops, but a considerable quantity undergoing saponi-
fication, as evidenced by the color of the potash solution. The
potash was then removed by filtration, the residue dissolved in
ether and extracted with boiling alcohol as before.

Four days after the evaporation of the alcohol, a large number
of the characteristic crystals were formed. These did not have the
split extremities and edges noted by Robin, but terminated in a
single point and had regular borders. The crystals are represented
in Fig. 14.

In a few days the entire mass had assumed a crystalline form,
and the crystals then presented split extremities and borders such
as are mentioned by Robin. (See Fig. 15.)

The quantity of stercorin was 10.417 grains.

Experiment X. — Another analysis was made of the feces from
the same individual. During the experiment a large quantity was
unfortunately lost, and the examination, therefore, was not quan-
titative. The presence of stercorin was established.

Experiment XI. — The feces of the dog from which blood of
the carotid and internal jugular on one side had been taken fifteen
days before, the animal having entirely recovered, were exam-
ined. The analysis was not quantitative. The feces were treated
in the way already described and the presence of stercorin de-
termined.

Experiment XII. — A specimen of feces voided by a healthy
dog, fasting, was examined in the usual way for stercorin. After
the final extract had evaporated, it was examined microscopically
and found to contain, in addition to stercorin, a considerable quan-
tity of cholesterin, crystallized in beautiful tablets. This is the

with boiling alcohol till nothing more can be extracted. A sediment deposits
from the alcohol on cooling. The alcoholic solution is acid. Milk of lime is
added to the solution, which gives a yellowish-brown precipitate, leaving a
clear straw-colored fluid. The precipitate is then collected on a filter, dried,
afterwards agitated with ether and filtered, forming a clear yellow solution. In
one to three days, beautiful silky crystals collect in masses, or tufts, adhering
to the sides of the vessel, throwing out ramifications in every direction. These,
viewed under the microscope, are in the form of acicular, four-sided prisms,
and this substance is called by Dr. Marcet, excretin, and is found nowhere
but in the feces. It is soluble in ether and hot alcohol, sparingly so in cold
alcohol, and insoluble in hot or cold water. It does not crystallize from an
alcoholic solution on cooling but crystallizes from ether. When suspended in
boiling water it fuses into resinous masses, and floats on the top. Its fusing
point is 203° to 205° Fahr. It may be boiled for hours with potash without
undergoing saponification.

In the article published in 1857, Dr. Marcet gives the composition of the
excretin Cts Hvs O2 S,.

There is no similarity between the form of the substance described by
Marcet and stercorin. Its high fusing point, 203° to 205° Fahr., and its
crystallization from an ethereal solution, also serve to distinguish it from
stercorin, which fuses at 96.8° Fahr. and does not crystallize from an ethereal
solution.

214 NEW FUNCTION OF THE LIVER

only examination of feces in which I have found cholesterin. The
proportion of stercorin and cholesterin was as follows :

Quantity of feces ' 37-5 ' 3 grains.

Stercorin with a little cholesterin 0.216 "

These examinations of the feces in health show that
they invariably contain a non-saponihable substance known
under the name of serolin, but which I have called ster-
corin. In but one of these analyses, the last, did I find
any cholesterin, though the first were originally undertaken
with a view to the extraction of this substance.

Stercorin has never before been detected in the feces;
and, so far as my knowledge of its physiological properties
is concerned, it may be considered a new substance, the
discovery of which, in this situation, marks it as one of the
most important of the products of destructive assimilation.
The next question which arises, then, is in regard to its
origin.

Origin of Stercorin. — In the study of the chemical
properties of this substance, it has been seen that it is one
of the non-saponifiable fats, having many characters in
common with cholesterin. It has been described, uiider
the name of serolin, as found in the blood in minute quan-
tity, but it does not exist in any of the fluids which are
poiu-ed into the alimentary canal. Cholesterin, however,
which it so closely resembles, is one of the constituents
of the bile. The fact that cholesterin is discharged into
the small intestine and is not usually found in the evacu-
ations, while stercorin is abundant, would at once point
to a possible connection between these two substances. In
most cases, in health, cholesterin disappears and stercorin
is found; but in some rare instances, as in the single exam-
ination of dogs' feces (Experiment XII.), the two sub-
stances coexist in the evacuations, stercorin, in the exam-
ple just mentioned, in much the greater quantity. The
question then arises: Is cholesterin capable of being con-
verted into stercorin, and does the latter substance orig-
inate from a transformation of the cholesterin of the bile?
Before treating of this subject experimentally, I shall ex-
amine the facts already ascertained bearing on this point.
No examinations of the feces have ever been made for ster-
corin; but under certain conditions cholesterin has been
found discharged by the anus without alteration.

NEW FUNCTION OF THE LIVER 215

Cholesterin has already been found in the meconium,
in the feces of hibernating animals and occasionally in
ordinary feces.

Meconium. — Cholesterin exists in meconium in con-
siderable quantity, where it may be seen in tablets in a
simple microscopic examination, and from which it may
be extracted in quantity and with great facility. Sterco-
rin (or serolin) has never been mentioned as existing in
this situation. In the single examination I have made of
the meconium, I found an abundance of cholesterin, 6.245
parts per 1,000, but no stercorin. There is no difficulty
in explaining the origin of the cholesterin in meconium.
Long before any food is taken into the alimentary canal
and before the exclusively digestive fluids are formed, the
bile is secreted and discharged. It accumulates in the in-
testine, with other matters constituting the meconium, and
is finally evacuated soon after birth. Hence cholesterin
exists in large abundance; but when the digestive fluids
are secreted and food is received into the alimentary canal,
the cholesterin is lost and stercorin makes its appearance.

Feces of Hibernating Animals. — As the excretory
function of the liver begins before food is taken into the
alimentary canal, so it goes on during the state of hiberna-
tion, when the animal takes no food for weeks or even
months. Under these conditions, cholesterin is found un-
changed in the feces; but it disappears when the animal
arouses and the digestive organs resume their functions.

Normal Feces. — In the normal feces cholesterin is
generally absent; but in Experiment XII., it was found
in small quantity, mixed with stercorin. This animal had
been certainly twenty-four hours, and probably forty-eight
hours without food. The feces were of normal color and
consistence.

These facts seem to show that before digestion begins,
as in the foetus, and when it is suspended, as in hibernating
animals and in Experiment XII., cholesterin passes
through the alimentary canal unchanged; but so soon as
digestion begins, cholesterin is lost in the feces and its
place is supplied by stercorin. It seems almost certain,
then, that in its passage down the alimentary canal, the
cholesterin of the bile is acted upon by some of the di-
gestive fluids and changed into stercorin. This change

2i6 NEW FUNCTION OF THE LIVER

seems to be incident to the digestive act; for before diges-
tion begins and when it is suspended, cholesterin passes
through unchanged. A conclusive observation would be
to cut off the bile from the intestines, and consequently
the cholesterin, and note the effect upon the production
of stercorin. In a case of jaundice from duodenitis (which
w'ill be more minutely detailed in the section on the path-
ological relations of cholesterin), the necessary conditions
for this observation seemed to be fulfilled. The patient suf-
fered from intense jaundice dependent upon obstruction
of the common bile duct from duodenitis. The feces were
clay-colored. After a time the patient was relieved of the
jaundice, and the feces regained their natural color. While
the feces were decolorized and when the icterus was most
marked, it is probable that the bile was entirely cut off
from the alimentary canal. This condition was relieved,
however, when the feces regained their color and the ic-
terus disappeared. For the purpose of ascertaining the
effect of the obstruction to the flow of bile on the ster-
corin of the feces and of the reestablishment of the flow,
the stools were examined chemically during the jaundice
and after the patient had recovered.

Analysis of Decolorized Feces. — The quantity of
feces examined was 941.4 grains. After evaporation, ex-
traction with ether and extraction of the residue left after
the evaporation of the ether with hot alcohol, the fat,
which was very abundant, was entirely saponified by boil-
ing for fifteen minutes with a solution of caustic potash,,
showing that neither cholesterin nor stercorin was present.

Analysis of Feces from the same Patient after
they had become Normal in Color. — This was made
nineteen days after the preceding analysis. The quantity
of feces was small. The specimen was treated in the usual
way, showing stercorin in the following proportion:

Quantity of feces 502.00 grains.

" stercorin 0.34 "

Taken in connection with the facts which have already
been cited in regard to the discharge of cholesterin by
the anus when digestion is not going on, this observation
seems to establish the origin of stercorin. It is produced
by a transformation, connected with the digestive act, of

NEW FUNCTION OF THE LIVER 217

the cholesterin of the bile. When cholesterin does not
find its way into the ahmentary canal, as was the case in
the first analysis of feces, stercorin is not found in the
dejections; when the discharge is reestablished, the ster-
corin reappears.

Comparison of the Daily Quantity of Stercorin

DISCHARGED, WITH THE QUANTITY OF ChOLESTERIN PRO-
DUCED BY THE Liver. — The quantity of stercorin which I
extracted from the regular daily feces of a healthy adult
male was 10.417 grains. As there is no cholesterin found
in the dejections, this should represent the entire quantity
of cholesterin excreted in the twenty-four hours. A com-
parison of this quantity with the estimated quantity of cho-
lesterin discharged in the day, shows this to be the case.

Quantity of bile in the twenty-four hours (Dalton) 16.940 grains.*

" " cholesterin at 0.618 pts. per 1,000 (Flint) 10.469! "

" " stercorin discharged (Id.) 10.417 "

Difference 052

This insignificant difference of 0.052 of a grain shows
at once the correctness of the estimate of the daily quan-
tity of bile excreted, the accuracy of the estimate of the
proportion of cholesterin in the bile and of the quantitative
analysis for stercorin; and made, as the three observations
were, without the slightest reference to each other, adds
the final link to the chain of evidence in support of the
view that cholesterin, in its passage down the alimentary
canal, is converted into stercorin, in which form it is dis-
charged in the feces.

The history of cholesterin thus resolves itself:

1. Cholesterin is an efifete material, produced by the
destructive assimilation of nervous matters and absorbed
by the blood.

2. It is separated from the blood in its passage through
the liver and enters into the composition of the bile, giving
this fluid its excrementitious character.

3. It passes with the bile into the upper part of the
small intestine, when the process of 'digestion induces a
change into stercorin, in which form it is discharged by
the feces.

* Dalton, " Treatise on Human Physiology," 2d edition, p. 171.
f See table, p. 173.

2i8 NEW FUNCTION OF THE LIVER

4. Stercorin, the principal excrementitious constituent
of the feces, is one of the most important excretions pro-
duced by the waste of the system.

Pathological Relations of Cholesterin. — With
the limited data on the subject of the variations in the
quantity of cholesterin in health and disease, it is impos-
sible to do more than merely to open the subject of
its pathological relations. To a certain extent, all ques-
tions in physiology have for an end the elucidation of
points in pathology. The practical physician who may
be the reader of this article will naturally inquire if the
more definite views which we are now enabled to hold in
regard to the function of the bile are of any use to him
in the study and treatment of disease. It is certain that no
addition to a knowledge of the functions of the healthy
body is without its bearings on disease, immediate or re-
mote. What may seem to be simply a matter of interest
to the pure physiologist, without apparently any practical
bearing, is sure at some time to become so connected
with other advances as to be useful to the practitioner.
But the pathological relations of an important excretion
do not have a practical interest so remote, especially when
this function is connected with the liver. Almost from
time immemorial, a large number of diseases have been
referred to derangement of the liver, and in their treatment,
it has been thought of immense importance to promote
the secretion of the bile. A certain class of remedies sup-
posed to regulate the secretion of bile has been con-
stantly employed by physicians. x\t the present day these
ideas have fallen somewhat into disrepute; for the enlight-
ened physician is now accustomed to base his pathological
views upon a certain amount of definite knowledge; and
it has been found that both the physiology and the pathol-
ogy of the bile have been very little understood. The older
practitioners had, as we have now, a certain class of cases
characterized by a general malaise, and having indefinite
symptoms that were attributed to " biliousness," in which
they were in the habit of employing the cholagogues, with
mercury at the head, with undoubted success. It is true
that as knowledge of disease becomes more accurate, the
conditions which were supposed to indicate " biliousness,"

NEW FUNCTION OF THE LIVER 219

have been referred to other disorders; but no great ad-
vance has been made in the pathology of the hver, and
there are yet many conditions which may be successfully,
though empirically, treated, the true character of which
is unknown. It is on this obscure subject that it is hoped
the preceding physiological investigations will throw
some light. To repeat a comparison made use of before,
a knowledge of the functions of cholesterin and its history
in the healthy organism should contribute as much to the
pathology of diseases dependent on derangement of this
function as the development of the functions of urea has
for diseases now known to be dependent on uremia.

CHOLESTEREMIA

In common with other excrementitious substances,
which invariably exist in the blood in health, if the func-
tion of the eliminating organ is interfered with, accumu-
lation takes place in the blood. This has already been
incidentally referred to in treating of the properties of
cholesterin w-hich allied it to effete substances. It takes
place as regards urea; but cases of uremic poisoning oc-
curred and patients died in uremic coma, long before the
cause of it was understood. It is the same with the bile.
Ordinary cases of jaundice, which have been called by
Piorry cholemia, are not of a dangerous character; but
there are cases in which jaundice, though less marked as
regards color, is a very different condition. Here is evi-
dently the operation of some poison in the blood; and
coma and death from its efifects on the brain follow as in
retention of the urea. Pathologists inquire why there is
this difference in the severity of cases of icterus. Chemists
have analyzed the blood in the hope of explaining it by the
presence of the glycocholates and taurocholates of soda in
the grave cases, regarding them as the only important
constituents of the bile; but their failure to detect these
substances has left the question still unanswered.

In cases of simple jaundice there is a resorption of the
coloring matter of the bile from the excretory passages.

In cases of grave jaundice, which almost invariably ter-
minate fatally, there is retention of cholesterin in the blood,
or cholesteremia.

220 NEW FUNCTION OF THE LIVER

I have been forced to make use of cases of disease ex-
clusively in studying- this condition, for no one has yet
been able, in the larger animals, to extirpate the liver, no-
tice the symptoms of poisoning and demonstrate the accu-
mulation of cholesterin in the blood. Nor have I yet been
able, on account of the insolul)ility of cholesterin, to make
experiments by injecting it into the circulation. I had,
however, an opportunity of making an examination of the
blood of a patient in the last stages of cirrhosis of the liver
accompanied with jaundice and compare it with an exam-
ination of the blood of a patient suffering from simple ic-
terus. Both of these patients had decoloration of the
feces; but in the first, the icterus was a grave symptom,
accompanying the last stages of disorganization of the
liver; while in the latter, it was simply dependent on duo-
denitis, the prognosis was favorable and was verified by
the result. As icterus accompanying cirrhosis is of infre-
quent occurrence, I deemed myself fortunate in having
an opportunity to compare the two cases.

Case I. Jaundice Dependent on Obstruction from Duode-
nitis.— Mary Bishop, ?et. 42, native of Ireland, widow, occupation
servant, was admitted into the Blackwell's Island Hospital, June 12,
1862, with the following symptoms : Slight febrile movement, with
severe pains over the duodenum ; the surface of the body was high-
ly icteric ; the stools were clay-colored ; urine high-colored, but
not examined for bile ; lungs and heart normal ; appetite rather
poor; no ascites. The icterus had existed since about May 23,
1862. The patient was confined to the bed.

Dr. Flint, the visiting physician, pronounced it a case of icte-
rus dependent on duodenitis.

Treatment. — Laxatives daily, with good diet and a moderate
quantity of stimulus.

June 21. A small quantity of blood was drawn from the arm
for examination, and on June 22,, the feces were collected for the
same purpose.

June 27. The patient remains about the same.

July II. All pain and tenderness over the duodenum have
disappeared. She has steadily improved since the last record. The
stools have been natural for several days. Though confined to the
bed most of the time, she is able to sit up two or three hours daily.
The jaundice has been gradually diminishing, and three or four
days ago it had entirely disappeared and is now absent.

July 12. Another specimen of the feces, which was of normal
appearance, was taken for examination.

Analysis of the Blood for Cholesterin. — The blood was ex-
amined about sixteen hours after it was taken from the arm. It had

NEW FUxNCTION OF THE LIVER 221

iully separated into serum and clot. The serum was of a bright
yellow color, more markedly bilious than in the succeeding case.
It was evaporated, pulverized, and a quantitative analysis for cho-
lesterin made, with the following results:

Quantity of blood 21 2.428 grains.

Quantity of cholesterin o. 108 "

Proportion of cholesterin per 1,000 pts. of blood 0.508 "

Case II. Jaundice with Cirrhosis. — Ann Thompson, ast. 39,
native of Ireland, occupation servant, was admitted into the Black-
well's Island Hospital June 16, 1862, and gave the following his-
tory:

Three months ago she contracted a severe cold, which was ac-
companied with swelling of the left hand and of both legs, continu-
ing for eight or nine weeks. At the end of that time she noticed
that the abdomen was increasing in size. She was then very weak,
the urine was scanty, bowels regular up to the time when she
entered the hospital. She denied having been in the habit of drink-
ing spirit, but acknowledged that she drank beer.

June 18. The surface of the body was icteric, the color was
very marked under the tongue and in the conjunctiva; the abdo-
men was full of fluid ; pulse 90, small and weak ; bowels loose and
the dejections clay-colored ; the urine highly tinged with bile and
copious ; appetite very poor. She was tapped, and about eight
quarts of clear, straw-colored serum were evacuated. The patient
was confined to the bed.

Dr. Flint, the visiting physician, diagnosticated cirrhosis.

The treatment consisted of sustaining measures, with stimu-
lants and the tinct. ferri muriat.

June 21. A small quantity of blood was taken from the arm
for examination, and on June 23, a specimen of the feces was
obtained for the same purpose.

The patient died June 27. There were no convulsions, and she
was sensible, though in a state of stupor, up to twenty minutes
before the fatal termination. The stupor existed three or four days
before death. Two days before, she complained of double vision.
The icterus was excessive up to the time of her death.

Autopsy. — The abdomen contained about twelve quarts of
liquid. The liver was examined. Its weight was 3 lbs. 12J- oz. It
was very light-colored, and had something of the " hob-nail " ap-
pearance, presenting, in short, the gross characters of cirrhosis.
The gall-bladder was very much contracted and contained only
about two drachms of bile. Microscopic examination of the organ
showed the liver-cells shrunken. The fibrous substance was in-
creased in quantity, and there were present a large number of
rather angular globules of fat.

Analysis of the Blood for Cholesterin. — The blood was ex-
amined about sixteen hours after it was drawn. It had fully sepa-
rated into serum and clot, and the serum was of a greenish-yellow
color. The whole, serum and clot, was then evaporated, pulver-

NEW FUNCTION OF THE LIVER

ized, and a quantitative analysis made for cholesterin in the man-
ner already indicated, with the following results:

Quantity of blood 50776 grains.

Quantity of cholesterin 0.093 "

Proportion of cholesterin per 1,000 pts 1.850

The following table gives a comparison of these results
with those obtained in the analyses of the three specimens
of healthy blood from the arm, which were examined at the
same time, and all five specimens subjected to identical
processes.

Table of Quantity of Cholesterin in Healthy Blood, Blood
FROM Simple Jaundice, and Jaundice with Cirrhosis

Blood of Jaundice

Cholesterin
per 1,000 pts.

Case I. Simple jaundice 0.508
" II. Jaundice with

cirrhosis. . . . 1.850

Healthy Blood

Cholesterin
per 1,000 pts.

Male, aet. 35 0.445

" 22 0.658

" " 24 0.751

Case I. Simple jaundice. Percentage of increase over

minimum of healthy blood. I4-I57

Decrease below maximum. . . 32.357

Case II. Jaundice with cirrhosis. Increase over minimum 315730

Increase over maximum 146.338

The results of the examination of the blood in these
cases of disease are striking and instructive. It has al-
ready been seen that the variations in health are very
considerable. In the three analyses here noted, the maxi-
mum was 0.751, and the minimum 0.445 P^s. per 1,000.
The conditions which regulate this variation it has not yet
been possible to study; but enough is known in regard
to it, to see that in the examination of blood in disease,
the cholesterin must mount considerably above the maxi-
mum or fall much below the minimum, to be considered
beyond the limits of health. But in the second specimen
of jaundiced blood, the variation from the limits of health
is so considerable as to admit of important physiological
and pathological deductions.

In the first place, what is the bearing of these observa-
tions on the physiology of cholesterin? As before re-
marked, no one has been able to remove the liver from a
living animal and note the effect upon the quantity of cho-

NEW FUNXTION OF THE LIVER 223

lesterin in the blood.* This experiment, if it were possible,
and if it showed that cholesterin increased in quantity and
killed the animal, would go to show that it was an ex-
crementitious substance and that it was removed by the
liver. But while the experimental physiologist contributes
much to the information of the pathologist by artificially
producing abnormal conditions, pathology furnishes a mul-
titude of useful experiments of Nature, which are invalu-
able to the physiologist. In the present instance, cases of
disease of the liver present a condition which can not at
present be imitated by experiments on the lower animals.
Disorganizing disease of the liver must interfere with its
excretory function, as Bright's disease does wdth the elim-
ination of urea; and if cholesterin is an excrementitious
substance to be removed by the liver, when the liver is seri-
ously affected with structural disease there should be an
accumulation of it in the blood. This, if fully established,
is positive proof of the character of cholesterin and the
function of the liver connected with its elimination.

What is to be learned, then, from a comparison of
the blood in Case 11. of jaundice dependent on cirrhosis
with healthy blood and a study of the history of the
case?

The cholesterin, in this instance, is enormously in-
creased in quantity, 315.730 per cent, over the minimum,
and 146.338 per cent, over the maximum. The case, as
far as symptoms are concerned, was of a very grave char-
acter. The patient not only suffered from an accumulation
of liquid, but there was evidently a poison in the system.
The patient died after three or four days of stupor, and on
post-mortem examination the liver was found disorgan-
ized. There was a deficient secretion of bile, and had been
for a long time; for the gall-bladder was much contracted
and the stools were clay-colored. In short the patient
died of cholesteremia; and the fact that this condition
can exist is a proof of the excrementitious function of

* Milller, Kunde and Moleschott have succeeded in removing the liver
from frogs and keeping them alive for two or three days — Moleschott preserv-
ing them for several weeks. These observations were made with reference
to the accumulation of the biliary salts and of the bile pigment in the blood,
their attention not having been directed to cholesterin. I began a series of
experiments on frogs, but they promised to be so prolonged that they were
deferred.

224 NEW FUNCTION OF THE LIVER

cholesterin, as uremia, as a toxemic condition, shows that
urea is an excretion.

Physiologically considered, this case fulfils an essential
condition of excrementitious substances; namely, accumu-
lation in the blood when the eliminating functions of the
excretory organs are interfered with. The liver became so
disorganized that its functions were seriously disturbed,
and the quantity of cholesterin in the blood increased to
a very great extent.

The pathological deductions from the facts which have
been elicited by examinations of the blood in these cases
seem to me of great importance. The literature of diseases
connected with disorders of the liver is full of theories,
more or less plausible, to explain certain conditions which
have long been established by clinical observation. There
are cases of simple jaundice which are not dangerous to
life, and sometimes, though the icterus is excessive, run
a certain course without interfering even with the ordinary
vocations of the patients. Again, there is jaundice which
is invariably fatal. The disease described by Frerichs un-
der the name of acute atrophy of the liver, and called by
some, acute jaundice, is one of the most serious diseases
of which there is any knowledge. The existence of this
great difference has led clinical observers to attribute the
mild cases to simple resorption of the coloring matter of
the bile, and the severe cases to a retention or resorption
of some of its more important constituents; especially as
it has also been observed that the symptoms which char-
acterize the latter condition occasionally occur in struc-
tural diseases of the liver without any discoloration of the
skin. But the pathology of this disease has been entirely
unknown. It has been thought that in such cases some
of the elements of the bile should exist in the blood. Fre-
richs says: " In the same way that urea accumulates in
large quantity in the blood in granular degeneration of the
kidneys, so ought the biliary acids and bile-pigment to
accumulate in the blood in cases of granular liver. Re-
peated observations have proved that this is not the case." *
Experiments on animals have been followed with like re-

* " A Clinical Treatise on Diseases of the Liver," by Dr. Fried. Theod.
Trerichs, Professor of Clinical Medicine, etc.. Berlin. Translated by Charles
Murchison, M. D. " The New Sydenham Society," London, i860, vol. i., p. 83.

NEW FUNCTION OF THE LIVER

225

suits. The frogs that were kept aHve by Moleschott for
weeks after the removal of the hver did not present a
trace of the biliary salts or bile-pigment in any part of
the system, showing that these matters are manufactured
in the liver. This obscurity, which leads to all sorts of
theories in regard to liver-pathology, must exist so long
as our knowledge of the physiology of the bile is so in-
definite. If observers had looked for cholesterin, a sub-
stance which preexists in the blood and is separated by
the liver, instead of the biliary salts, w^iich do not pre-
exist in the blood, are manufactured in the liver, as these
experiments tended to show, and are pecuHar to the bile,
they would have met with different results. The very fact
that the biliary salts are peculiar to the bile and found in
no other fluid should have led them to disregard these sub-
stances in their analyses of the blood, because this stamps
them as secretions and distinguishes them from excretions.
They should have looked for some substance which exists
in the blood as well as the bile, an indispensable condition
of an excretion, and this substance is cholesterin.

Understanding, therefore, the physiological relations of
cholesterin, jaundice may be divided into two varieties:
simple icterus, or yellowness, and a condition which I have
called cholesteremia. Cholesteremia may occur, also, with-
out discoloration of the skin.

Simple Icterus. — In simple icterus there is a resorp-
tion of the coloring matter from the biliary passages. As
it has been shown that the coloring matter of the bile
appears first in the liver, when it exists in the blood it is
not due to accumulation but to resorption. In these cases
the resorption is generally due to obstruction of the biliary
passages. The patient suffers only from the disease which
causes the obstruction, and from the derangement of di-
gestion which is due to the absence of bile from the intes-
tinal canal. In those cases in which there is no organic
disease of the liver, there is no danger of absorption of
cholesterin. This is a condition analogous to retention of
urine. The patient suffers simply from retention of
bile in the excretory passages, and cholesteremia is no
more to be expected from obstruction of the bile-duct
without structural changes of the liver, than uremia is to
be looked for in vesical retention of urine without organic
15

226 NEW FUNCTION OF THE LIVER

change in the kidneys. Excretions are not reabsorbed,
akhough they may be retained in the blood.

The quantity of cholesterin in the blood is not neces-
sarily increased in simple icterus; for the liver is still per-
forming its function of elimination, and when once sepa-
rated from the blood it is not taken up again. The analysis
of the blood in Case I. indicated a proportion of 0.508
parts per 1,000, which is within the limits of health, a little
below the mean, probably on account of the somew'hat
enfeebled condition of the patient.

The feces may or may not be decolorized, this depend-
ing on the extent of the obstruction to the passage of
bile into the intestine. The obstruction to the flow of bile
frequently is relieved before the system has time to re-
move the coloration of the skin, and the feces become nor-
mal while the patient is icteric. In some instances there
is no change in the appearance of the dejections during the
course of the disease. When the dejections are entirely
decolorized there is an absence of stercorin, into which
the cholesterin is transformed before it is discharged, with
an abnormal quantity of fat w-hich has passed through un-
digested.* Stercorin reappears in the feces when the flow
of bile is reestablished and they assume their normal color.

The two following analyses were made of the feces in
Case I.: one, when they were entirely decolorized and the
patient was very much jaundiced, and the other, when she
had recovered and the dejections had assumed their nat-
ural appearance.

Feces of Case I. Jaundice Dependent on Duodenitis. First
Analysis. — The feces were clay-colored and apparently free from
bile. They weighed 941.4 grains. They were evaporated to
dryness without difficulty, pulverized, digested with f?iij of ether
for twenty hours, filtered through animal charcoal, evaporated and
extracted with hot alcohol. The fatty residue after evaporation
of the alcohol was very abundant.

The residue was then treated with a solution of caustic potash
and exposed to a gentle heat. In fifteen minutes it became entirely
saponified, forming a clear homogeneous soap with no residue,
showing the absence of stercorin. The soap was boiled down and

* This fact, which has often been remarked, seems to indicate that the bile
is actively concerned in the digestion of the fats. I have noticed that dogs
with biliary fistulae, though with a ravenous appetite, refuse to eat fat meat.
This disinclination to eat fat has been noticed in cases of jaundice with de-
coloration of the feces.

NEW FUNCTION OF THE LIVER 227

molded into a cake, which I preserved and which weighs thirty-
four grains. The following is the result of the examination :

Quantity of feces 94' -4 grains.

"fat 39- 1 24 "

Percentage of fat 4- ' 44

No stercorin or other non-saponifiable fats.

Feces Nineteen Days After. Second Analysis. — At that
time the patient had entirely recovered from the jaundice, and
the feces had regained their natural appearance. A small speci-
men was taken for chemical examination, which was made, em-
ploying the process already described for the extraction of ster-
corin, with the following result:

Quantity of feces 503 grains.

" " stercorin 0.340 "

Cholesteremia with Icterus. — In jaundice compli-
cated with blood-poisoning there exists a very different
state of things as regards gravity of symptoms and prog-
nosis. This occurs in acute jaundice, or when it accom-
panies and is dependent upon structural change in the
liver, as the jaundice of cirrhosis. The difference in the
pathology of these cases, coinpared with those of simple
icterus, has long been recognized; but, as before remarked,
analysis of the blood has failed to throw any light on the
subject, because chemists directed their attention exclu-
sively to the biliary salts. Frerichs says:

" I have myself repeatedly examined jaundiced blood, which
has been obtained by venesection, or still more frequently, from the
heart or vena cavse of the dead body, for the biliary acids, and
their immediate derivatives ; and more recently I have had it ex-
amined by my assistant. Dr. Valentin, but always with negative
results. No substance could be found in the alcoholic extract of the
blood which yielded any indication, by Pettenkofer's test for the
biliary acids, whether this alcoholic extract was treated directly
with sulphuric acid and sugar, or whether, in order to get rid of
foreign substances, a watery extract of it was first prepared. This
coincides with the experience of most of the older observers." *

In cases of blood-poisoning by retention and accumu-
lation of elements of the bile in the blood, the important
pathological condition is a great increase in the quantity
of cholesterin. The fact of accumulation of this substance
in the blood in certain cases of icterus, has been noticed
by Becquerel and Rodier; but they did not connect it with
structural change in the liver and did not explain its physi-

* Frerichs, op. cii., p. 95.

228 NEW FUNCTION OF THE LIVER

ological or pathological importance. The fact of its accu-
mulation in the blood is strong evidence of its excrcmenti-
tious character; but this does not appear to have attracted
the attention of the observers just mentioned. The follow-
ing is one of the cases in which increase of cholesterin
was observed by them, the only one in which they allude
to its significance, and here merely to state their inability
to explain it:

" The second case is nearly similar, excepting the phlegmasia,
which did not exist. It relates to a boy, nineteen years of age, a
li)iwnadicr, affected for some time with a bilious diarrhoea, with
fever, and icterus, recently developed and very marked. There
existed in the blood of this patient a slight diminution of the
globules (136) ; albumen in normal quantity (71.4) ; likewise fibrin
(2.3); fatty matter sufficiently abundant; serolin in an imponder-
able quantity; cholesterin excessively abundant (0.798) ; soaps abun-
dant (2.032). To what cause must we attribute this great quantity
of cholesterin? How and why is it concentrated in the blood in
spite of the biliary flux? This is what it is difficult to decide."*

What I have shown in regard to the physiology of cho-
lesterin removes the difficulty in the explanation of this
fact. In Case II. there was the rare complication of jaun-
dice with cirrhosis, the symptoms evidently pointing to
poisoning by retention of some toxic element in the blood.
Examination of the blood in this case showed that choles-
terin existed in the proportion of 1.850 parts per 1,000;
the minimum of healthy blood being 0.445 ^'^'^^ the maxi-
mum 0.751 parts. Taking this case as an example, there
is cholesteremia with jaundice, presenting symptoms which
characterize the retention of bile in the blood, which are
already well known and were established long before it was
possible to say what toxic element was retained. Cases
in which jaundice exists with cholesteremia are so different
from cases of ordinary jaundice that there is no difficulty
in making the discrimination by symptoms. When jaun-
dice exists with cirrhosis, it is probable that there always is
cholesteremia. In aciite jaundice the symptoms, especially
those referable to the nervous system, are so marked that
the gravity of the case is easily recognized. I have no
doubt that in such cases cholesterin is immensely increased
in the blood, although on account of their rarity I have
not had an opportunity of determining this by analysis.

* Translated from Becquerel and Rodier, op. cit., p. 210.

NEW FUNCTION OF THE LIVER 229

Icterus with cholesteremia and simple icterus are quite
distinct from each other. The only feature they have
in common is the discoloration of the skin. Simple icterus,
which is comparatively harmless, is not likely to run into
the more severe variety, which can not occur without struc-
tural change in the liver; while the grave variety occurs
when there is evidence of organic disease of the liver or
when the case presents symptoms from the first which indi-
cate its serious character. The one has no more constitu-
tional danger than exists in a simple case of spasmodic
retention of urine; while the other has characters as grave
as those which attend uremic poisoning due to disorgan-
ization of the kidney.

In these cases the feces may show a very marked de-
ficiency of bile; but this is due to the deficient, but not
arrested secretion of this fluid, while the clay-colored stools
in simple icterus are dependent on the want of discharge
of the bile into the intestine. While in the latter instance,
as in Case I., one would expect to find no stercorin in the
dejections, in the former, one would expect to find ster-
corin, though in greatly diminished quantity. Further
examination of the feces in cases of structural disease of
the liver will be of advantage as indicating, by the quan-
tity of stercorin found, the extent to which the elimina-
tive function of the liver is disturbed.

The following analysis was made of the feces in Case
II. of jaundice dependent on cirrhosis:

Feces of Case II. Jaundice Dependent on Cirrhosis. — The
feces were clay-colored, though the decoloration was not quite so
marked as in the Case I. of simple jaundice.

The specimen was evaporated with great difficulty. It was
reduced to a black, glutinous mass which could not be pulverized.
It was treated twice with alcohol, the alcohol evaporated, and once
with ether. After the ether had evaporated the residue was pul-
verized and analyzed for stercorin, with the following result :

Quantity of feces 272. i grains.

Stercorin 0.077 "

This analysis showed a very great diminution in ster-
corin in the feces, the normal quantity in the daily pas-
sages, according to the single examination I have made,
being 10.417 grains. The specimen of feces was the ordi-
nary quantity passed daily. It showed that cholesterin

230 NEW FUNCTION OF THE LIVER

was still eliminated, though not with sufficient activity to
prevent its accumulation in the system. This was further
evidenced by the post-mortem examination, when the gall-
bladder was foun(l contracted but containing a small quan-
tity of bile.

Examination of the blood and feces of the patient suf-
fering from cholcsteremia with jaundice thus leads to the
following conclusions:

1. Cholesterin was largely increased in the blood show-
ing that the structural change in the liver had interfered
with its elimination.

2. Stercorin was correspondingly diminished in the
feces, showing that the cholesterin was not discharged in
normal quantity into the alimentary canal.

Cholesteremia without Icterus. — From a practical
point of view, this condition is one which it is very im-
portant to be able to recognize; but here is felt most the
necessity of more extended investigations than it has been
possible to make. I have been able only to open the
subject by the analysis of one or two specimens of blood
taken from patients who had organic change in the liver,
but no jaundice. One of the most familiar of these affec-
tions of the liver consists in those changes of structure
included in the term cirrhosis. Frerichs describes a con-
dition which he calls acholia, denoting suppression of
the functions of the liver. This is the condition which
I have called cholesteremia, which expresses the con-
stituent of the bile which produces the toxic effects, the
action of which was unknown to Frerichs; while the term
acholia expresses retention of bile without giving any
idea of the active morbific agent. Further investigation
will undoubtedly establish more fully what the analyses I
have made thus far seem to show; namely, that in what
Frerichs calls acholia without jaundice, there is the choles-
teremic condition that exists in acholia with jaundice. The
following quotation from Frerichs' treatise on the liver
gives an idea of one of the conditions in which there is
acholia (or cholesteremia) with or without jaundice.*

" Cases have repeatedly occurred to me, in which individuals
who for a long period have suffered from cirrhosis of the liver,

* Frerichs, op. cit., p. 241.

NEW FUNCTION OF THE LIVER 231

have suddenly presented a series of symptoms which are foreign
to that disease. They have become unconscious, and have been
afterwards seized with noisy deHrium, from which they passed to
deep coma, and in this state have died. In one case there was
spasmodic contraction of the muscles of the left side of the face.
In most cases, slight jaundice made its appearance at the same
time, and in one instance there were petechise. Upon post-mortem
examination, not the slightest lesion could be detected in the brain,
neither were there indications of any acute disease which could
account for the derangement of the cerebral functions. The liver,
in all cases, presented cirrhotic degeneration in a marked degree,
and the glandular cells were for the most part loaded with fat ;
large quantities of leucine separating from it ; the bile ducts con-
tained only a small quantity of pale bile."

In certain cases of organic disease of the liver, and prob-
ably in all cases accompanied by the grave symptoms men-
tioned by Frerichs, there is cholesteremia ; but this charac-
ter does not exist in all cases where the liver is affected,
any more than uremia exists in all cases of structural dis-
ease of the kidney. Nature not only provides organs which
are sufficient for the removal of effete matters from the
blood, but provides for conditions in which the fimction of
these organs may be partly interrupted, and yet the excre-
tion go on, a part taking on the function of the whole.
One of the kidneys may be removed, and yet the other,
increased in size it is true, is capable of performing the
function of both. The kidneys may be partially disorgan-
ized, and yet the sound portion be sufficient for the de-
purative function, and urea will not accumulate in the
blood. So it is with the liver. There are patients with
partial disintegration of this organ, as in some cases of
cirrhosis, suffering apparently but little inconvenience from
the disease and presenting none of the symptoms of cho-
lesteremia. But when the liver is extensively affected, so
much so that it can not separate the cholesterin effectually
from the blood, there is cholesteremia. I have made an
analysis of the blood of two patients affected with cirrhosis
who presented this contrast as regards the symptoms of
cholesteremia. In one of them, Case III., there was con-
siderable constitutional disturbance; and in the other, Case
lY., the patient was about and suffered no great incon-
venience, though he had been tapped for ascites more
than thirty times.

232 NEW FUNCTION OF THE LIVER

Case III. Cirrhosis with Ascites and Considerable Affec-
tion OF the General Health. — Mary Perkins, ret. 23, native of
Ireland, prostitute, has been a spirit-drinker for about seven years.
About the ist of May, 1862, she noticed an enhirgenient of the ab-
domen, which was accompanied with pain over the region of the
hver, when she took to the bed. She states that at that time the
stools were dark green. Fluid continued to accumulate in the
abdomen, and was drawn off in the hospital (Blackwell's Island),
June 25. About six quarts of a clear, straw-colored serum were
removed, but a little was left in the abdomen, as the patient was
very weak. The patient improved after the removal of the fluid,
which did not reaccumulate in any considerable quantity. The
liver was found diminished in size, and from this and other cir-
cumstances, the diagnosis was cirrhosis.

June 28. A specimen of blood was taken from the arm for
examination. She left the hospital July 6, and was confined to the
bed until within a few days of her discharge.

Analysis of the Blood for Cholesterin. — The blood pre-
sented nothing peculiar in its appearance. A quantitative analysis
W'as made for cholesterin, with the following result :

Quantity of blood 1 17-193 grains.

" " cholesterin o. 108 "

Proportion of cholesterin per 1,000 pts. of blood 0.922 "

Case IV. Cirrhosis with Ascites and Slight Constitu-
tional Disturbance. — Thomas Hughes, ?et. about 33, brewer, pre-
sented himself at the Long Island College Hospital, July i, 1862,
with Dr. Dugan, of Williamsburg. He confessed that he had been
in the habit of drinking more or less spirit daily for the past ten
years. The abdomen began to swell about eighteen months ago.
The ascites was preceded by hematemesis, when he vomited an
abundance of black, clotted blood. The belly immediately began to
swell and enlarged rapidly. He took hydragogues under the direc-
tion of a physician, and the dropsy disappeared, but returned when-
ever the medicines were discontinued. Qidema of the lower limbs
occurred soon after the ascites. He has had recurrence of hema-
temesis twice since the first attack.

He was first tapped two or three months after the affection
occurred and has been tapped about thirty times since. He was
tapped last on June 27th. He is tapped and goes out the next day.
He thinks nothing of it and is always for the time relieved. He
has continued to drink beer daily and some spirit. After tapping
his appetite is good, and food occasions no inconvenience. When
the abdomen is full, food occasions a distressing distention, so that
he does not eat freely.

The urine is scanty when the abdomen is full, and is free after
tapping.

There is no pain in the belly or elsewhere. He is about all
day but is not engaged in business. He says he is not very feeble..
He presents a notably anemic aspect.

The abdomen is now moderately full (July l). Superficial

NEW FUNCTION OF THE LIVER 233

veins of abdomen much enlarged. Heart appears not enlarged; a
feeble systolic murmur over the body of the organ.

Several months before the ascites began, he got into a fracas
and was badly beaten. He v^as not laid up, but says he did not
feel w^ell afterward and is disposed to attribute his disease thereto.

Advised to continue to tap when the abdomen refills, with
tonics, hygienic measures, and abstinence from spirit, continuing
the use of ale moderately. (Private records of Dr. Flint.)

July I. A specimen of blood was taken from the arm for ex-
amination.

Analysis of the Blood for Cholesterin. — The blood was
treated in the usual way, and a quantitative analysis was made for
cholesterin, with the following result:

Quantity of blood 251.567 grains.

" " cholesterin 0.962 "

Proportion of cholesterin to 1,000 pts. of blood. 0.246 "

The following table shows the comparative quantity of
cholesterin in these specimens and in the three specimens
of healthy blood:

Healthy Blood

Cholesterin
per 1,000 pts.

Male, aet. 35 0.445

" " 22 0.658

" " 24 0.751

Blood of Cirrhosis

Cholesterin
per 1,000 pts.

Case III. Cirrhosis (se-
vere) 0.922

Case IV. Cirrhosis (mild) 0.246

Case III. Cirrhosis (severe). Percentage of increase in

cholesterin over minimum

of healthy blood 107.190

Ditto over maximum 22.769

Case IV. Cirrhosis (mild). Percentage of decrease in

cholesterin below mini-
mum of healthy blood. . . 42.469

These two cases present a very striking contrast; and
the chemical examination of the blood has shown as
marked a difference in the quantity of cholesterin as in
the gravity of the attendant symptoms. They teach, how-
ever, an important lesson. There is not always an accu-
mulation of cholesterin in the blood when the structure
of the liver is altered, it being requisite that this alteration
should involve enough of the organ to interfere with the
elimination of this substance. The quantity may even fall
below the natural standard in a patient who is rendered
anemic by the consequences of a cirrhosis which is not
sufficient to induce cholesteremia. The process of nutri-
tion being thereby diminished in activity, the production

234 NEW FUNCTION OF THE LIVER

of this substance, by destructive assimilation, is necessarily
diminished. The cholesteremia may be slight and tran-
sient; for the causes which produce it may be, to a certain
extent, temj^orary. In Case III. the patient was confined
to the bed, suffering acute pain over the region of the liver,
in all probability due to a slight degree of inflammation.
This interfered with the excretion of cholesterin, and its
proportion in the blood was increased to 22.769 per cent,
over the maximum, and 107.190 over the minimum.* As
the patient was somewhat enfeebled by syphilis before the
symptoms of disease of the liver made their appearance,
it is probable that the quantity of cholesterin in the blood
did not equal the highest standard in health. At all
events, there was a notable increase even over the maxi-
mum quantity. Case IV. is not less instructive. Here
is a patient who has had cirrhosis of the liver, with ascites,
for eighteen months, and has been tapped more than thirty
times. He apparently has suffered from nothing more than
the mechanical effects of the liquid, which has interfered
at times with digestion, and rendered him anemic. He is
tapped and immediately relieved, going out the next day.
There seems to be no interference with the functions of the
liver, so far as the symptoms are concerned, other than
the mechanical obstruction to the circulation; and the
case, as regards symptoms, resembles cases of ovarian
dropsy where the patient carries about an immense quan-
tity of water, but suffers only from this, and is relieved
temporarily when the water is removed. Considering
the condition of the patient, one should not be surprised
to find the cholesterin of the blood not increased, but di-
minished in quantity; and one may, I think, come to the
conclusion from the symptoms as well as the analysis of
the blood, that though the liver was affected sufficiently
to produce obstruction of the circulation, there w^as not
sufficient disease to give rise to cholesteremia.

It is evident that much more extended observations are
necessary in order to establish the clinical relations of cho-
lesteremia without jaundice; but the case of Mary Perkins
shows that this condition does exist, while the case of
Thomas Hughes shows that it does not follow structural

* Unfortunately the character of the stools was not noted.

NEW FUNCTION OF THE LIVER

235

Table of Quantitative Analyses for Cholesterin

Human blood from the arm. Healthy male set. 35

" " " xt. 22

" " " " " ret. 24

" " " Simple jaundice

" " " Cholesteremia with jaundice

" " " Cirrhosis (grave)

" " «' " (mild)

" " " Hemiplegia —

Case I. Paralyzed side.

Sound side . . .

Case II. Paralyzed side.

Sound side . . .

Case III. Paralyzed side.

Sound side . . .

Blood from carotid )

" " internal jugular \ Dog experiment

" " femoral vein )

" ;; carotid ( j3 experiment \

" " mternal jugular ) •= ^ (

" " carotid )

" " internal jugular > Dog experiment

" " femoral vein )

" " carotid )

" " portal vein > Dog experiment

" " hepatic vein )

Human brain (subject killed instantly)

" (Case n., killed instantly)

Human bile (specimen from Case II.)

Crystalline lens (4 lenses from the ox)

Meconium

Quantity

Cholesterin

examined.

peri,ooopts.

grains.

312.083

0.445

187.843

0.658

102.680

0-751

212.428

0.508

50.776

1.850

117-193

0.922

251.567

0.246

55-458

128.407

0.481

18.381

66.396

0.808

21.824

52.261

0.579

179.462

0.774

134.780

0.801

133.886

0.806

140.847

0.768

97.811

0.947

143.625

0.967

29.956

1-545

45-035

1.028

159-537

1-257

168.257

1.009

79.848

0.964 ■

159-753

7.729

150.881

11.456

224.588

0.618

135.020

0.907

170.541

6.245

change in the Hver unless the lesion is extensive. The
fact that there may be contamination of the blood by the
retention of a biliary matter, without discoloration of the
skin, is exceeding important; and of this there seems to me
to be no doubt. A patient who has structural disease of
the liver and presents symptoms of blood-poisoning is suf-
fering from cholesteremia, although there is no icterus.
The cholesteremia may vary in degree between the mild-
ness which characterized Case IIL, in which it was, per-
haps, temporary,* and the grave condition mentioned by
Frerichs, characterized by noisy delirium and coma, and
announcing a speedy fatal termination. Adding to these

* The patient having gone out of the hospital, it was impossible to settle
this point.

236 NEW FUNCTION OF THE LIVER

conditions the cases of what is ordinarily called bilious-
ness, attended with drowsiness, an indefinite feeling of
malaise, constipation, etc. (and all this relieved by a simple
mercurial purge, which is said to promote the secretion
of the liver), is it not to be hoped that some light will be
thrown on their pathology by a knowledge that there is a
condition called cholesteremia! As yet this is but specu-
lation; but the discovery of the important function of cho-
lesterin opens a wide field of inquiry in this direction; and
ere long the physician may be able to speak of '' bilious-
ness," and " liver complaint," with some definite ideas of
their pathology.

The table on page 235 gives the results of the quanti-
tative analyses for cholesterin which have been referred
to in this article.

CONCLUSIONS

The observations contained in the preceding article
seem to me to justify the following conclusions:

1. Cholesterin exists in the bile, the blood, the nervous
matter, the crystalline lens and the meconium, but does
not exist in the feces under ordinary conditions. The
quantity of cholesterin in the blood of the arm is five to
eight times more than the ordinary estimate.

2. Cholesterin is formed, in great part if not entirely,,
in the substance of the nervous matter, where it exists in
great abundance, from which it is taken up by the blood
and constitutes one of the most important of the effete
or excrementitious products of the body. Its formation
is constant, and it always exists in the nervous matter and
the circulating fluid.

3. Cholesterin is separated from the blood by the liver,
appears as a constant constituent of the bile and is dis-
charged into the alimentary canal. The history of this
substance, in the circulating fluid and in the bile, marks it
as a product destined to be discharged from the body, as
an excretion. It preexists in the blood, subserves no useful
purpose in the economy, is separated by and not formed in
the liver, and if this separation is interfered with, it accu-
mulates in the system.

4. The bile has two separate and distinct functions de-
pendent on the presence of two constituents of entirely

NEW FUNCTION OF THE LIVER 237

different characters. It has a function connected with nu-
trition. This is dependent on the presence of the glyco-
cholate and taurocholate of soda, which do not preexist
in the blood, subserve a useful purpose in the economy
and are not discharged from the body, are found in the
liver and peculiar to the bile, do not accumulate in the
blood when the function of the liver is interfered with, and
are, in short, products of secretion. The bile has another
function connected with depuration, which is dependent
on the presence of cholesterin, which is an excretion.
The flow of the bile is remittent, being much increased
during the digestive act, but produced during the intervals
of digestion for the purpose of separating cholesterin from
the blood.

5. The ordinary normal feces do not contain choles-
terin, but contain stercorin — formerly called serolin, from
its being supposed to exist only in the serum of the blood.
Stercorin results from a transformation of the cholesterin
of the bile during the digestive act.

6. The change of cholesterin into stercorin does not
take place when digestion is arrested or before this pro-
cess begins; consequently, stercorin is not found in the
meconivmi or in the feces of hibernating animals during
their torpid condition. These matters contain cholesterin
in large abundance, which also sometimes appears in the
feces of animals after a prolonged fast. Stercorin is the
form in which cholesterin is discharged from the body.

7. The difference between the two familiar varieties
of jaundice, one characterized only by yellow-ness of the
skin and comparatively innocuous, while the other is at-
tended with very grave symptoms and is almost invariably
fatal, is dependent upon the obstruction of the bile in
one case and its suppression in the other. In the first in-
stance, the bile is confined in the excretory passages and its
coloring matter is absorbed; while in the other, cholesterin
is retained in the blood.

8. There is a condition of the blood dependent upon
the accumulation of cholesterin which I have called clioles-
teremia. This occurs only when there is structural change
in the liver, which incapacitates it from performing its ex-
cretory function. It is characterized by symptoms of a
grave character, referable to the brain, and probably is

238 NEW FUNCTION OF THE LIVER

dependent upon the effects of the retained cholesterin on
this organ. It occvirs with or without jaundice.

9. Cholesteremia does not occur in all cases of struc-
tural disease of the liver. Enough of the liver must be
destroyed to prevent the due elimination of cholesterin.
In cases in which the organ is but moderately affected, the
sound portion is capable of performing the eliminative
function of the whole.

10. In cases of simple jaundice, when the feces are de-
colorized and the bile is entirely shut off from the intestine,
stercorin is not found in the evacuations; but in cases of
jaundice with cholesteremia, stercorin may be found,
though always very much diminished in quantity, showing
that there is an insufficiency in the separation of the cho-
lesterin from the blood, although its excretion is not en-
tirely suspended. After death, but a small quantity of bile
is found in the gall-bladder.

PLATE I

Fig. 4.

Fig. 5.

PLATE II

I6

Fig. 9.

Fig. 10.

PLATE III

Fig. 14.

Fig. 15.

EXPLANATION OF THE PLATES

Fig. I. — Cholesterin extracted from meconium. j\ inch objective.

Fig. 2. — Stercorin and fatty matters from the blood of the carotid
artery. ^ inch objective.

Fig. 3. — Cholesterin and small broken crystals of stercorin from
the same specimen of blood from the carotid, examined
eleven days after. Nachet, No. 3 objective.

Fig. 4. — Cholesterin from the brain. \ inch objective.

Fig. 5. — Cholesterin from the blood of the internal jugular, with
a few needles of stercorin. ^ inch objective.

Fig. 6. — Cholesterin and stercorin from the same extract as Fig. 5,
examined the next day. ^ inch objective.

Fig. 7. — Cholesterin and stercorin from the blood of the vena cava.
^ inch objective.

Fig. 8. — Cholesterin from the blood of the portal vein. A inch
objective.

Fig. 9. — Cholesterin from the blood of the hepatic artery. -J inch
objective.

Fig. 10. — Cholesterin and stercorin from the blood of the hepatic
artery, i inch objective.

Fig. II. — Fatty substances from the blood of the hepatic vein. ^
inch objective.

Fig. 12. — Cholesterin and stercorin from the same specimen, ex-
amined the following day. -| inch objective.

Fig. 13 — Cholesterin extracted from bile, i inch objective.

Fig. 14. — Stercorin from human feces. -j-V inch objective.

Fig. 15. — Stercorin from the same specimen, after it had been
melted, placed on a glass slide, covered with thin glass,
and allowed to crystallize. The crystallization was
very slow, occupying some weeks. This Fig. shows
splitting of the borders and points of the crystals with
the globules referred to on page 207. The globules
were of variable size, and some of them were arranged
in rows, which, with an inferior microscope, might be
mistaken for varicosities on the needles. From their
appearance in this specimen, after it had been thor-
oughly purified, I am inclined to change the opinion
expressed on page 207, and regard them as composed
of stercorin and not fatty impurities. ^ inch objective.

X

THE EXCRETORY FUNCTION OF THE LIVER

Published in the " Transactions of the International Medical Congress," held
in Philadelphia in September, 1876.

I HAVE selected as the subject which I 'shall have the
honor to present to the Section on Biology, the Excretory-
Function of the Liver, for the reason that it seemed to me
better to discuss a question concerning which I had made
personal and original investigations than to recite the ob-
servations of others, however interesting and important
the latter might be. I have ventured to assume that the
views which I have to offer are not without importance;
.and they are certainly not so familiar as many other topics
which I might with propriety have selected. I shall, there-
fore, endeavor to bring to your notice, in the simplest man-
ner possible, what I have myself learned in regard to the
liver as an organ of excretion.

It is now well known that the liver has a variety of
important functions with which physiologists are more or
less acquainted. The liver produces a substance which
is converted into sugar and is carried away in the torrent
of the circulation. It secretes bile which performs an im-
portant office in digestion. In addition to the digestive
function of the bile. I think I have shown that this fluid
serves as the vehicle for the elimination of at least one
excrementitious matter, which is discharged in a modi-
fied form in the feces. If the liver serves as an organ of
excretion, it is evidently of great importance, from a path-
ological as well as a physiological point of view, to arrive at
an accurate knowledge of the mechanism of this function.
For a long time, many pathological conditions have been
attributed to defective or perverted action of the liver;
but the terms, " liver complaint," " biliousness," etc., have
failed to convey any definite pathological idea, and it is

239

240 EXCRETORY FUNCTION OF THE LIVER

probably true that the liver has been accused of many
sins of omission and commission without any positive
scientific reason. Many medical writers have assumed, in
an indefinite way, that the liver possesses an excretory
function; but so far as I know, no physiologist has de-
scribed any definite excrementitious substance eliminated
by this organ prior to my observations in 1862.

There are certain general laws applicable to secretions
and to excretions, which it is important to consider in dis-
cussing the functions of the bile:

I. Secretions have some useful purpose to serve in the
economy, and. as a rule they are not discharged from the
body in health. Excretions have no function in the econ-
omy and are discharged from the body.

II. The flow of secretions from the glands usually is
intermittent, occurring when their function is called into
action. The flow of excretions usually is either constant
or remittent.

III. The production of excretions depends upon the
general process of disassimilation, which is constant. The
production of secretions has no relation to disassimilation,
but is connected with processes which usually take place
at intervals.

IV. The elements of secretion, which give to secreted
fluids their characteristic physiological properties, are
formed de novo in the glands themselves out of materials
furnished by the blood, and they do not preexist ready-
formed in the circulating fluid. The elements of excretion
preexist in the blood, being taken up by the lymph or by
the blood from the tissues, and they are separated from
the blood by organs which have no part in their actual pro-
duction; except that excrementitious substances may be
changed one into another, as creatin into creatinin or uric
acid into urea.

V. When secreting organs are removed or destroyed,
there is no vicarious" production of the peculiar constitu-
ents of the secretions; these elements do not accumulate
in the blood; and the system suffers simply from the ab-
sence of the function of the special secretion. When ex-
creting organs are removed or destroyed, there may be a
vicarious elimination of the excrementitious matters by
other organs or the system may suffer toxic effects from

EXCRETORY FUNCTION OF THE LIVER 241

the accumulation of excrementitious matters in the circu-
lating fluid.

VI. The characteristic constituents of true secretions
generally are reabsorbed by the blood; but they are taken
up in a modified form, so ihat they are not to be recog-
nized in the circulating fluid. Elements of excretion are
with difficulty reabsorbed by the blood after they have
once been separated by the proper organs.

The applications of the foregoing general laws may be
readily made to the pancreatic juice as contrasted with the
urine, which two fluids may be taken as types respectively
of secretions and of excretions. Before making an appli-
cation of these laws to the bile, we may consider the simple
question as to whether it can be shown that this fluid has
a useful function to perform as a secretion. If the bile
has no such function, an animal would live and maintain
its normal condition when the bile is diverted from the in-
testine and discharged from the body. This question has
been made the subject of experimental observation by
simply cutting off the bile-duct and making a fistula into
the gall-bladder, by which the bile is discharged. The oper-
ative procedure involved is not difficult, but is very likely
to be followed by fatal peritonitis, so that few experiments
of this kind have succeeded. In the experiments which
have succeeded, in the hands of Schwann, Bidder and
Schmidt, Nasse, Bernard and myself, the dogs have lived
for thirty or forty days, dying with all the symptoms of
inanition. In one remarkably successful experiment per-
formed by myself, the dog lived for thirty-eight days, had
a voracious appetite and died at the end of that period
after having lost about four-tenths of his weight. In this
experiment the bile-duct was ligatured in two places and
the intermediate portion was exsected. A fistula was then
made into the fundus of the gall-bladder, which was kept
open. The animal ate well on the day of the operation,
and there was very little peritonitis. The only observation
in which contrary results were obtained is one made by
Blondlot.* In this case a fistula was made into the gall-
bladder after the bile-duct had been divided. The animal

* Blondlot, " Essai sur les fonctions du foie et de ses annexes," Paris, 1840,
p. 55 et seq. ; and " Inutilite de la bile dans la digestion," Paris, 1851.

242 EXCRETORY FUNCTION OF THE LIVER

lived for five years, and after fifteen days following the
operation, was in good flesh and apparently suffered no
inconvenience from the discharge of the bile from the
fistula. During the first fifteen days the animal licked the
bile from the fistula, but this was afterward prevented by
a muzzle. After a time he made no attempt to lick the
bile. Blondlot attributed the emaciation which occurred
during the first fifteen days to this licking of the bile.
When the animal died, more than five years after the oper-
ation, an examination of the parts was made in the pres-
ence of several physicians and students of medicine and
no communication could be found between the bile-duct
and the intestine. From this observation Blondlot con-
cluded that the bile had no function in digestion and that
it was a purely excrementitious fluid; and he assumed that
the cause of death in other experiments of a similar kind
was the licking of the bile as it flowed from the fistula.
In my own case of biliary fistula, in which the dog died
after thirty-eight days, the animal was prevented by a muz-
zle from licking the bile.

The only point to consider, as it seems to me, in this
single experiment of Blondlot, is whether or not a com-
munication had been reestablished between the bile-duct
and the intestine. If such a communication existed, it
would be easy to explain the survival of the animal. The
following experiment, which I undertook for a different
purpose, satisfied me upon this point:

I attempted to estimate in a dog the entire quantity
of bile discharged in the twentv-four hours. With this
object in view, I cut down upon the bile-duct, emptied the
gall-bladder, secured a canula in the duct and attached a
rubber-bag to the canula for the purpose of collecting the
bile. Twenty-three hours after the operation the bag was
in place and nearly full of bile. Just before the end of the
twenty-four hours, however, the animal ruptured the bag,
and the experiment, so far as its original object was con-
cerned, was a failure. I then simply pulled the canula from
the wound and set the animal at liberty. In about four
weeks, after the wound had closed and the feces had be-
come of normal color, the animal, when in a perfectly
normal condition, was killed and the parts were carefully
examined in the presence of several assistants. It is well

EXCRETORY FUNCTION OF THE LIVER 243

known that in dogs ducts that have been divided have a
remarkable tendency to become reestabHshed. In this
case, inasmuch as no bile was discharged externally and
the feces were of normal color, it was certain that the
bile was discharged into the intestine. Nevertheless I
searched for more than an hour for the communication
before it was discovered. The only reasonable way, as it
appears to me, to reconcile the single experiment of Blond-
lot with those of other observers is to suppose that in
his observation a communication between the bile-duct
and the intestine had become established, which he failed
to find. The difficulty which I experienced in finding the
communication in my own observation led me to conclude
that a communication existed in the case reported by
Blondlot. which he did not discover.

It is in accordance with my own observations, as well
as with those of other physiologists, to conclude that the
bile is a secretion, and that it has a function to perform
in connection with the digestive process, which function
is essential to life.

Assuming that the bile has an important and an essen-
tial office in digestion, is it not possible that it may also
serve the purpose of elimination, and contain elements of
excretion! This is a view which has not been advanced
by physiologists, who have regarded the bile either as a
secretion or an excretion and have not imagined that it
could serve both functions. Before I take up the experi-
mental facts bearing upon this question. I propose to con-
sider the arguments to be drawn from a study of the com-
position of the bile and its discharge into the intestine.
It was this idea which first led me to investigate the physi-
ological relations of cholesterin.

The bile certainly has an important function as a se-
cretion; and its flow, although not intermittent, is more
abundant during the process of intestinal digestion. The
peculiar biliary salts, the glycocholate and the taurocho-
late of soda, are formed in the liver and do not preexist
in the blood. When the structure of the liver is invaded
by disease so as to interfere with the production of bile,
the biliary salts do not accumulate in the blood. The bil-
iary salts are reabsorbed in a modified form in the intestine;
for the quantity of one of their elements (sulphur) found

244 EXCRETORY FUNCTION OF THE LIVER

in the feces is very much less than the quantity discharged
into the intestine.

On the other hand, in regard to one constant con-
stituent of the ]n\e (cholesterin), it is not known to have
any function in connection with digestion. The secretion
of bile is continuous, although its flow is increased during
digestion. Cholesterin, while it is an invariable constitu-
ent of the bile, exists in the blood and in certain of the
tissues of the body.

The questions to determine experimentally in regard
to cholesterin are the following:

Is cholesterin produced in any of the tissues of the
body?

Is cholesterin separated from the blood by the liver?

When the liver undergoes structural change in disease,
does cholesterin accumulate in the blood?

Is cholesterin reabsorbed in the intestine or is it dis-
charged, either unchanged or in a modified form, in the
feces?

These are the questions which I endeavored to answer
by a series of experimental investigations, made in the
spring of 1862, and published in October of the same year,
in the " American Journal of the Medical Sciences."

Process for the Estimation of Cholesterin in
THE Blood. — The following is the process which I fixed
upon, after a num1)er of trials, for the quantitative analysis
of the blood for cholesterin: The entire blood, serum and
clot, is evaporated to dryness. The dry residue is then
pulverized in an agate mortar and treated for tw-elve to
twenty-four hours with ether, in the proportion of about
one fluidounce of ether to one hundred grains of the orig-
inal w-eight of blood. This is filtered, and the ethereal ex-
tract, which contains cholesterin and fats, is evaporated.
The residue of this evaporation is then extracted with boil-
ing alcohol, in the proportion of one fluidrachm for one
hundred grains of the original w^eight of blood. This ex-
tract is filtered while hot and the filtrate is evaporated,
leaving the cholesterin and a certain quantity of saponi-
fiable fats. To remove the saponifiable fats, add to the
residue a weak solution of potash, and allow it to remain
for about two hours; then dilute with water, filter, and

EXCRETORY FUNCTION OF THE LIVER 245

wash the filter with water until the liquid which passes
through becomes neutral. Dry the filter; wash it with
ether; evaporate the ether; extract the residue with hot al-
cohol as before; evaporate the alcoholic extract, and the
residue will consist of cholesterin, perfectly pure, as can
be determined by means of the microscope. Using this
process for the determination of cholesterin, a number of
observations were made upon dogs, from which I select
the following as typical, the results having been repeat-
edly confirmed:

Observation I. Experiment showing an Increase in Choles-
terin IN the Blood passing through the Brain. (The dog
was not etherized.)

Blood from the carotid, 140.847 grains, contained 0.108 grain
of cholesterin, or 0.768 part of cholesterin per 1,000.

Blood from the internal jugular, 97.811 grains, contained 0.092
grain of cholesterin, or 0.947 part of cholesterin per 1,000.

The increase in the proportion of cholesterin in the blood in
pasing through the brain was 23.309 per cent.

This observation, which was frequently repeated with
the same general result, seems to show that the blood
gains cholesterin in its passage through the brain. It is
well known that cholesterin is always present in nervous
substance, not in a crystallized form, but in a condition of
molecular union with nitrogenous and other matters. In
order to verify this fact, I examined the brains of two sub-
jects who had been killed instantly by accident while in
perfect health, in one case finding a proportion of choles-
terin of 7.729 parts per 1,000, and in the other, 11.456
parts per i ,000.

The experiment just described was made with a view
of determining whether or not the brain gives up choles-
terin to the blood as it circulates through this organ; and
the following experiment was made to determine whether
the venous blood of other parts contains an excess of cho-
lesterin. Theoretically, the blood of the femoral vein
should contain a little more cholesterin than arterial blood,
this excess being derived from the nerves of the extremity,
although the increase would probably be not so great as
in the blood of the internal jugular, which comes almost
exclusively from the great nervous centre.

246 EXCRETORY FUNCTION OF THE LIVER
Observation II. Experiment showing an Excess of Choles-

TERIN IN THE BlOOD OF THE INTERNAL JUGULAR AND FeMORAL

Veins over the Arterial Blood. (The dog was not ether-
ized.)

Blood from the carotid, 143.625 grains, contained 0.679 grain
of cholesterin, or 0.967 part of cholesterin per 1,000.

Blood from the internal jugular, 29.956 grains, contained 0.046
grain of cholesterin, or 1.545 part per 1,000.

Blood from the femoral vein, 45.035 grains, contained 0.046
grain of cholesterin, or 1.028 part per 1,000.

The increase in the pro|)ortion of cholesterin in the blood in
passing through the brain was 59.772 per cent.

The increase in the proportion of cholesterin in the blood in
passing through the lower extremity was 6.308 per cent.

Thi.s experiment confirms the previous observation
upon the increase of cholesterin in the blood in passing
through the brain, and it shows, in addition, that the
blood gains cholesterin in other parts. Inasmuch as the
nervous tissue is the only tissue in the extremities which
contains cholesterin. it is probable that the excess con-
tained in the blood of the femoral vein over the arterial
blood was derived from the nerves.

It occurred to me that cases of old hemiplegia would
present favorable conditions for verifying in the human
subject the observations made on the lower animals. It
has been ascertained that when the function of nerves
is permanently abolished they soon become degenerated
and their nutrition is modified; and it seems probable that
if cholesterin is one of their important products of dis-
assimilation, the quantity of cholesterin in the blood from
paralyzed parts should be very small. Taking the blood,
for example, from the paralyzed arm of a hemiplegic, this
blood, coming from paralyzed parts, should contain less
cholesterin than the blood from the sound arm. Of course,
the blood from the arm contains no blood which has passed
through the brain, which is assumed to be sound upon the
paralyzed side. I examined, therefore, the blood from both
arms in three cases of hemiplegia in the Charity Hospital
on Blackwell's Island:

Case I. — Sarah Rumsby, set. 47, is affected with hemiplegia of
the left side. Two years ago she was taken with apoplexy and was
insensible for three days. When she recovered consciousness she
found herself paralyzed on the left side. She says she had epilepsy
four or five years before the attack of apoplexy. She has now

EXCRETORY FUNCTION OF THE LIVER 247

complete paralysis of motion on the affected side, with the excep-
tion of some slight power over the fingers. Sensation is not af-
fected. The speech is perfect and her general health is good.

Case II. — Anna Wilson, aet. 23, is affected with hemiplegia of
the right side. Four months ago she became unconscious and re-
covered in one day, with loss of motion and sensation on the right
side. She is now improving and can use the right arm slightly.
The leg is not so much improved because she will make no eft'ort
to use it.

Case III. — Honora Sullivan, set. 40, is affected with hemiplegia
of the right side. About six months ago she became unconscious,
recovering the next day, with paralysis. The leg was less affected
than the arm from the first. Her condition is about stationary as
regards the arm- but the leg has somewhat improved.

A small quantity of blood was drawn from either arm
in these three cases. In each instance it was drawn from
the paralyzed side with difficulty and btit a small qtiantity
could be obtained.

The specimens were all examined for cholesterin, with
the following results:

Observation III. Quantities of Cholesterin in the Blood of the
Paralyzed and the Sound Sides in Three Cases of Hemiplegia

Cases.

Blood.

Cholesterin.

Cholesterin per i,ooo parts.

Case I.

Paralyzed side. . . .

Sound side

Paralyzed side. . . .

Sound side

Paralyzed side. . . .
Sound side

grains.
55-458

128.407
18.381
66.396
21.842
52.261

grains.

The watch-glass contained
0.031 grain of substance,
but the most careful ex-
amination with the mi-
croscope failed to show
crystals of cholesterin.

0.481.

Same as in Case I.

Case II

0.062

Case III

0.062

0.808.

Same as in Case I.

0.031

0,579.

The conclusion from the experiments upon dogs and
the three observations upon the human subject is inevita-
ble, that cholesterin is produced in the substance of the
brain and in the nervous tissue generally, as this substance
is not contained in the mitscular tissue or in any other
parts except the crystalline lens, the liver and the spleen.
The question now to determine is the relation of choles-
terin to the nervous system. Is it one of the products of
disassimilation of its tissue? If this is the fact, choles-
terin is an excrementitious product and it must be sepa-

248 EXCRETORY FUNCTION OF THE LIVER

rated from the blood by some organ or organs and dis-
charged from the body. Inasmuch as the bile always con-
tains cholesterin, we naturally look to the liver as the
organ for its elimination; for it is not found in the secre-
tion of any other gland.

1 employed essentially the same method in studying
the (juestion of the elimination of cholesterin as that used
in determining the seat of its production, analyzing the
blood going to and coming from the liver. Upon this
point I made a number of observations, the general results
of which were invariable. The following experiment is a
type of these observations:

Observation IV. Experiment showing that Cholesterin is

SEPARATED FROM THE BlOOD IN ITS PASSAGE THROUGH THE

Liver. (The dog was etherized.)

Arterial blood, 159.537 grains, contained 0.200 grain of choles-
terin, or 1.257 P'li't of cholesterin per 1,000.

Blood of portal vein, 168.257 grains, contained 0.170 grain of
cholesterin, or 1.009 P'^''^ of cholesterin per 1,000.

Blood of hepatic vein, 79.848 grains, contained 0.077 grain of
cholesterin, or 0.964 part of cholesterin per 1,000.

The loss in the proportion of cholesterin in arterial blood in
passing through the liver was 23.309 per cent.

The loss in the proportion of cholesterin in the portal blood in
passing through the liver was 4.460 per cent.

The bile always contains a certain proportion of cho-
lesterin, which I found, in a specimen taken from the gall-
bladder of a subject who had been killed instantly wdiile
in perfect health, to be 0.618 part per 1,000. As I have
demonstrated that the blood gains cholesterin in its pas-
sage through the brain and probably also from the gen-
eral nervous tissue, that cholesterin is separated from the
blood in its passage through the liver, and that cholesterin
is invariably found in the bile and is discharged into the
intestine, it seems to be proved that one of the functions
of the liver is to eliminate this substance. If it can be
shown that the cholesterin thus separated from the blood
by the liver is discharged from the body, the fact that it
is apparently produced in the nervous tissue and is taken
up by the blood would point strongly to the conclusion
that cholesterin is an excrementitious matter and is
one of the products of disassimilation of the nervous
tissue.

EXCRETORY FUNCTION OF THE LIVER 249

Stercorin. — I made repeated examinations of the nor-
mal feces, with the view of determining the presence of cho-
lesterin and its quantity. Although it is often stated by
authors that cholesterin exists in the feces, I was unable
to find it after the most careful examination; and I subse-
quently failed to discover any writer who had actually ex-
tracted it from the normal dejections. The process Vvhich
I employed was essentially the same as that used in exam-
inations of the blood, except that the extracts were de-
colorized by filtering through animal charcoal, and the
alcoholic extract was treated with potash for one or two
liours at nearly the boiling point. Treated in this way,
the feces gave an extract which was non-saponifiable but
which did not crystallize for several days. After a few
days, delicate, needle-shaped crystals began to appear,
gradually increasing in number and breadth, and as they
became broader, becoming split at the points and edges.
These crystals presented all the characters of the crystals
of a substance extracted from the serum of the blood
by Boudet, in 1833 (" /\nnales de chimie et de physique "),
which he called " seroline." In some of my earlier ob-
servations upon the
blood, I obtained these
■crystals; but I came to
the conclusion that the
so-called seroline was
not a normal constitu-
ent of the blood but
Avas formed during the
process used for the
•extraction of choles-
terin. With this view,
finding the so-called
seroline to be a con-
stant constituent of
the normal feces, I
called the substance
stercorin, regarding it
as one of the excre-
mentitious constituents of fecal matter. Crystals of ster-
corin are shown in the accompanying figure. The round-
ed drops probably are composed of the same substance, as
17

Stercorin from normal human feces (-,% inch
objective).

250 EXCRETORY FUNCTION OF THE LIVER

they disappear when the crystallization is complete. The
idea that these crystals obtained from blood result from
the transformation of cholesterin is strengthened by the
tact that the cholesterin of the bile is changed into ster-
corin in its passage through the alimentary canal. Sterco-
rin, like cholesterin, is soluble in ether, very soluble in hot
alcohol and strikes a red color with strong sulphuric acid.

I obtained from the feces of the twenty-four hours of
a perfectly healthy man 10.417 grains of stercorin. It is
estimated by Dalton that the total quantity of bile in twen-
ty-four hours is 16,940.00 grains, and the total quantity
of cholesterin, according to my estimate of 0.618 parts
per 1,000, is 10.469 grains, giving a difference between the
estimated quantity of cholesterin and the actual quantity
of stercorin extracted from the feces of only 0.052 of a
grain. This sustains the idea of the change of the choles-
terin of the bile into the stercorin of the feces.

Observations made by myself and others seem to show
that the change of cholesterin into stercorin is incidental
to the process of digestion. Cholesterin is found in quan-
tity in the feces of hibernating animals and in the meco-
nium, when, of course, there is no intestinal digestion, but
when the bile is none the less discharged into the alimen-
tary canal. I made an examination of human meconium
and found cholesterin in the proportion of 6.245 parts per
1,000 and no stercorin. I examined the human feces in
a case of simple jaundice from obstruction of the bile-duct,
the feces being clay-colored, and found neither cholesterin
nor stercorin. Nineteen days after, w'hen the jaundice had
disappeared and the color of the feces was normal, I found
stercorin and no cholesterin. In the feces of a dog which
had been deprived of food for forty-eight hours. I found
stercorin and a small quantity of cholesterin. So far as
can be learned from these facts and observations, then, it
seems that the cholesterin of the bile is discharged in the
feces unchanged when no digestion takes place, but that
it is discharged in the form of stercorin under the ordinary
and normal conditions of the digestive process.

Pathological Relations of Cholesterin. — Cho-
LESTEREMiA. — A knowledge of the relations of urea to nu-
•trition bears so directly upon the pathology of renal dis-

EXCRETORY FUNCTION OF THE LIVER 251

eases, that the pathological relations of any newly-discov-
ered excrementitious matter assumes at once the greatest
importance. If it is true that cholesterin, like urea, is a
product of disassimilation, and that it is eHminated by the
liver as urea is eliminated by the kidneys, one would ex-
pect to find, in cases of serious structural disease of the
liver, an accumulation of cholesterin in the blood, or cho-
lesteremia, as uremia exists in certain stages of extensive
organic disease of the kidneys. It has long been observed,
indeed, that although simple jaundice due to resorption
of the coloring matter of the bile usually is a trivial affec-
tion, there are cases of extensive change in the structure
of the liver in which there is apparently a toxic condition
dependent upon the presence of some excrementitious or
poisonous substance in the blood. Pathologists have ex-
amined the blood in such cases wdth the view of ascertain-
ing the nature of the supposed poisonous matter. Frerichs
and others repeatedly examined the blood in cases of grave
jaundice, expecting to discover the biliary salts or acids,
but they never detected any substance which would react
with Pettenkofers test.* Becquerel and Rodier exam-
ined the blood in a case of jaundice and found " cholesterin
excessively abundant," but they did not recognize the sig-
nificance of this fact.t In such cases pathologists have
looked for the bihary acids and their derivatives and not
for cholesterin. In order to throw some light upon the
pathology of grave jaundice, Muller,:|: Kunde,* Lehmann,||
and Moleschott ^ have extirpated the liver in frogs and
kept the animals alive for several days, or even two or
three weeks. On examining the blood, these physiologists
failed to discover the biliary salts. They made no analyses
of the blood for cholesterin. I hope to be able to show^
conclusively, by observations upon cases of disease of the
liver in the human subject, that there may be an accumu-
lation of cholesterin in the blood, or cholesteremia, and
that this occurs in certain cases of serious structural dis-
ease of the liver.

* Frerichs, "Diseases of the Liver," London, 1S60, vol. i., p. 95-

+ Becquerel et Rodier, "Traite de chimie pathologique," Paris, 1854, p. 210.
X Miiller, " Manuel de physiologie," Paris, 1851, tome i., p. 122.

* Kunde, " De Hepatis Extirpatione," Berolini, 1850.

II Lehmann, " Physiological Chemistry," Philadelphia, 1855, vol. i., p. 476
^ Moleschott, " Comptes rendus," Paris, 1855, tome xl., p. 1040.

252 EXCRETORY FUNCTION OF THE LIVER

In cases of simple jaundice there is resorption of the
coloring matter of the bile from the excretory passages.

In cases of grave jaundice, which almost invariably ter-
minate fatally, there is cholesteremia, or accumulation of
cholesterin in the blood.

There are cases of structural disease of the liver in
which there is no jaundice, but nevertheless there is cho-
lesteremia.

In the following cases, having first determined the pro-
portion of cholesterin in normal blood, I examined the
blood for cholesterin with 'reference to the points just
stated:

Observation V. Proportion of Cholesterin in Normal
Blood. —

Male, ast. 35 0-445 part of cholesterin per i ,000.

" " 22 0.658 " " "

" 24 0.751

Observation VI. Case of Jaundice Dependent probably
UPON Duodenitis. — This case presented the symptoms of simple
jaundice from temporary obstruction of the bile-duct. June 21,
1862, 212.428 grains of blood were taken from the arm. The pro-
portion of cholesterin per 1,000 was 0.508, which is within the
limits of health, according to the results obtained in my examina-
tions of normal blood. The feces, which were clay-colored, were
examined, and I found neither cholesterin nor stercorin. July 11,
the patient had entirely recovered; there was no jaundice, and the
feces had become normal.

Observation VII. Case of Grave Jaundice with Cirrhosis.
— This case presented intense jaundice, ascites, great general pros-
tration, and toward the close of life, symptoms of blood-poisoning.
The patient was admitted to the Charity Hospital on Blackwell's
Island, June 16, 1862. On June 21 50.776 grains of blood were
taken from the arm. This blood contained a proportion of 1.850
part of cholesterin per 1,000, an increase of 146.338 per cent, over
the maximum quantity obtained from normal blood. The patient
died June 27, 1862. There was double vision six days before death
and stupor for the last three or four days. The liver, examined
after death, was in a condition of cirrhosis. The gall-bladder was
contracted and contained but about two drachms of bile. The
fibrous substance of the liver was increased in quantity and the
liver-cells were shrunken. The feces were taken a few days before
death. The amount was small, only 272.1 grains in twenty-four
hours, and contained 0.077 of ^ grain of stercorin. I found 10.417
grains of stercorin in the feces of the twenty-four hours in a
healthy male.

Observation VIII. Case of Cirrhosis with Ascites and
Considerable Affection of the General Health. — In this case

EXCRETORY FUNCTION OF THE LIVER 253

there was general prostration confining the patient to the bed.
After a tapping, the hver was explored and found to be consider-
ably diminished in size; 1 17.193 grains of blood were taken from
the arm, containing a proportion of 0.922 of a part of cholesterin
per 1,000, an increase of 22.769 per cent, over the maximum pro-
portion obtained in my examinations of normal blood. In this case
there were no nervous symptoms.

Observation IX. Case of Cirrhosis with Ascites and
Slight Constitutional Disturbance. — This patient had suffered
from ascites for eighteen months and had been tapped about thirty
times. He is immediately relieved by tapping and goes out the
next day. July i, 1862, 251.567 grains of blood were taken from
the arm, which gave a proportion of cholesterin of 0.246 of a part
per 1,000, or 44.719 per cent, less than the minimum obtained in
my examinations of normal blood.

The cases just detailed, taken in connection with my
observations upon animals, are certainly very striking. In
the case of simple jaundice, which recovered, the propor-
tion of cholesterin in the blood was within the limits of
health. In the case of ascites, the patient not suffering
much disturbance, the proportion of cholesterin in the
blood was considerably below the normal standard. In
the case of grave jaundice, which terminated fatally with
symptoms of serious disturbance of the nervous system,
the proportion of cholesterin in the blood was enormously
increased, being nearly three times greater than the maxi-
mum obtained in my examinations of normal blood. In
the case of cirrhosis with considerable affection of the gen-
eral health, the proportion of cholesterin in the blood was
considerably above the maximum obtained in my exam-
inations of normal blood.

Literature bearing upon the " New Excretory Function of
THE Liver," since the Publication of my Observations in
1862

October, 1862. — j\Iy researches were published in the " Ameri-
can Journal of the Medical Sciences."

1868. — A translation of my memoir into French was published
in Paris and presented to the Academy of Sciences for the Mon-
thyon prize.

1869. — The commission from the French Academy of Sciences
reported upon my observations and awarded an " honorable men-
tion " with a " recompense " of fifteen hundred francs.

1869. — Grollemund ("These de Strasbourg") made observa-
tions upon the injection of the biliary salts into the blood in large
quantity in dogs, and noted certain disturbances of the nervous
system.

254 EXCRETORY FUNCTION OF THE LIVER

1869. — Tincclin ("These de Strasbourg") made observations
in which he failed to obtain any marked nervous disturbances fol-
lowing the injection of the biliary salts into the blood in dogs.

1869. — Pages ("These de Strasbourg") injected the bile-duct
in dogs with a solution of sulphate of iron, which he thought de-
stroyed the epithelium of the liver and interfered with its elimina-
tive function, producing accumulation of cholesterin in the blood.

1870. — Feltz and Ritter ("Journal de I'anatomie," Paris, 1870)
confirmed the results obtained by Pages with the sulphate of iron.
They found no marked effects following the injection of the biliary
salts, taurin or glycochol into the veins. They also injected cho-
lesterin in soap and water. The cholesterin was not dissolved, and
masses of cholesterin were found in the small pulmonary vessels,
producing death by embolism.

1872. — Picot ("Journal de Tanatomie," Paris, 1872) noted an
accumulation of cholesterin in the blood in a case of acute yellow
atrophy of the liver which terminated fatally. He found a pro-
portion of cholesterin in the blood in this case of 1.804 P^^t per
1,000, more than double the maximum which I obtained in exam-
inations of normal blood.

1873.— Koloman Miiller (" Archiv fiir experimentelle Patholo-
gic und Pharmakologie," Leipzig, 1873) made an elaborate series
of experiments upon dogs. No serious or marked results followed
the injection of the biliary salts or taurin into the blood. He
rubbed cholesterin with glycerin and made a solution in soap and
water. He injected 2.16 fiuidounces of this solution, containing
about 69 grains of cholesterin, into the veins. In five experiments
he produced " a complete picture of the symptoms of grave jaun-
dice."

Conclusions of Koloman Muller. — " It appears to me to be
certain that those cerebral symptoms which accompany severe jaun-
dice and many diseases of the liver, the general manifestations of
which have been called ' cholemic intoxication,' are produced by
an abnormal accumulation of cholesterin in the blood. This accu-
mulation of cholesterin is contingent upon that alteration of the
tissue of the liver, which, in such cases, it suffers more or less."

1875 and 1876. — Feltz and Ritter ("Journal de I'anatomie,"
Paris, 1875 and 1876) in opposition to their former experiments,
conclude that the biliary salts injected into the blood produce grave
changes, mainly in the blood corpuscles. The corpuscles become
diffluent, change their form, the hemoglobin transudes and crystal-
lizes, and the power of absorption of oxygen progressively dimin-
ishes.

The general results of observations bearing upon the
physiological relations of cholesterin, made since 1862, are
confirmatory of my observations. As regards cholestere-
mia. the experiments of Muller are the most important.
Indeed, they supply the only missing link in my chain of
experimental evidence; and they show conclusively that the

EXCRETORY FUNCTION OF THE LIVER 255

symptoms of " grave jaundice," which I connected with
cholesteremia, may be produced by the artificial introduc-
tion of cholesterin into the circulation.

As an inevitable result of my observations, confirmed
by others and extended by Koloman Miiller, I can now
confidently repeat the conclusions which I published in
1862.

CONCLUSIONS

I. Cholesterin exists in the bile, the blood, the nervous
matter, the crystalline lens and the meconium, but does
not exist in the feces under ordinary conditions. The
quantity of cholesterin in the blood of the arm is five to
eight times more than the ordinary estimate.

II. Cholesterin is formed, in great part if not entirely,
in the substance of the nervous matter, where it exists in
great quantity and from which it is taken up by the blood
and constitutes one of the most important of the effete,
or excrementitious products of the body. Its formation
is constant and it always exists in the nervous matter and
the circulating fluid.

III. Cholesterin is separated from the blood by the
liver, appears as a constant element of the bile and is dis-
charged into the alimentary canal. The history of this
substance, in the circulating fluid and in the bile, marks
it as a product destined to be discharged from the body
as an excretion. It preexists in the blood, subserves no
useful purpose in the economy, is separated by and not
formed in the liver, and if this separation is interfered
with, it accumulates in the system.

IV. The bile has two separate and distinct functions
dependent on the presence of two constituents of entirely
difTerent characters. It has a function connected with
nutrition. This is dependent on the presence of the glyco-
cholate and taurocholate of soda, which do not preexist
in the blood, subserve a useful purpose in the economy and
are not discharged from the body, are found in the liver
and peculiar to the bile, do not accumulate in the blood
w^hen the function of the liver is interfered with, and are,
in short, products of secretion. The bile has another func-
tion connected with depuration, which is dependent on
the presence of cholesterin, which is an excretion. The

25.6 EXCRETORY FUNCTION OF THE LIVER

ilovv of bile is rcmiltciit. l)cini; much increased during the
(hgestive act, but produced (hu-ing the intervals of diges-
tion for the purpose of separating cholesterin from the
blood.

V. The ordinary normal feces do not contain choles-
terin but contain stercorin — formerly called " seroline "
from its being supposed to exist only in the serum of the
blood. Stercorin results from a transformation of the
cholesterin of the bile during the digestive act.

VI. The change of cholesterin into stercorin does not
take place when digestion is arrested or before this pro-
cess begins; consequently stercorin is not found in the
meconium or in the feces of hibernating animals during
their torpid condition. These matters contain cholesterin
in large abundance, which also sometimes appears in the
feces of animals after a prolonged fast. Stercorin is the
form in w^hich cholesterin is discharged from the body.

VII. The difference between the two familiar varieties
of jaundice, one characterized only by yellowness of the
skin and comparatively innocuous, wdiile the other is at-
tended with very grave symptoms and is almost invari-
ably fatal, is dependent upon the obstruction of the bile
in one case, and its suppression in the other. In the first
instance, the bile is confined in the excretory passages and
its coloring matter is absorbed; while in the other, choles-
terin is retained in the blood.

VIII. There is a condition of the blood dependent
upon the accumulation of cholesterin, which I have called
cholesteremia. This occurs only when there is structural
change in the liver which incapacitates it from performing
its excretory function. It is characterized by symptoms
of a grave character referable to the brain and probably
is dependent upon the effects of the retained cholesterin
on this organ. This occurs with or without jaundice.

IX. Cholesteremia does not occur in every instance
of structural disease of the liver. Enough of the liver
must be destroyed to prevent the due elimination of cho-
lesterin. In cases in which the organ is but moderately
afTected, the sound portion is capable of performing the
eliminative function of the whole.

X. In cases of simple jaundice, when the feces are de-
colorized and the bile is entirely shut off from the intestine^

EXCRETORY FUNCTION OF THE LIVER 257

stercorin is not found in the evacuations; but in cases of
jaundice with cholesteremia, stercorin may be found,
though always very much diminished in quantity, showmg
that there is an insufficiency in the separation of the cho-
lesterin from the blood, although its excretion is not en-
tirely suspended. After death, but a small quantity of
bile is found in the gall-bladder.

XI

STERCORIN AND CHOLESTEREMIA *

Published in the " New York Medical Journal " for June 5, 1S97.

Looking far into the future, it seems possible that our
successors may fix upon the month of May, 1946, as the
true centennial of the American Medical Association, dat-
ing the origin of this body from May, 1846, when a con-
vention of representatives of our ])rofession, held in New
York, proposed the formation of a National Association,
which was formally organized in 1847. If your orator
of to-day finds it impossible to do justice to this occa-
sion, how much more difficult will it be to present, in a
single address, an adequate picture of a full century of
medical progress! The year 1946 will be the centennial
of the application of anesthesia to surgery. It will be
the third jubilee of the crowning glory of the eighteenth
century, the completion of the discovery of vaccination,
when the terrible scourge, smallpox, which had been more
destructive to human life than war or famine, w^as virtually
subdued. At the Jenner Centenary, held in Berlin in May,
1896, Yirchow stated, as an ethnological fact, that " all
peoples that had not been reached by vaccination or that
had not accepted it had disappeared from the face of the
earth, destroyed by smallpox." Will the orator of 1947
be able to point to a triumph of American medicine equal
to the application of anesthesia a hundred years before
or to the beginning of an era in preventive medicine, like
that inaugurated by the immortal Jenner! Looking into
the future, it is possible that in fifty years smallpox will
have disappeared from the face of the earth, like the peo-
ples it has destroyed. But who can say, in the light of

* Address on Medicine delivered at the semicentennial anniversary of the
American Medical Association, in Philadelphia, June 2, 1897.

258

ANNIVERSARY ADDRESS 259

what has been accompHshed within our own recollection,
what may not be done within the next half-century! In
the single line of preventive medicine, is it not possible
that we may be able to secure immunity from tuberculosis,
typhus and typhoid fevers, scarlatina, diphtheria and other
infectious maladies, and that these diseases may disap-
pear! As it is now, even with a not inconsiderable popu-
lar prejudice against vaccination, many successive years
have passed in the city of New York without one case
of smallpox; and medical knowledge is becoming daily
more progressive and more generally accepted by the laity.

It is not too much to say that the convention of May,
1846, marked an era in the history of medical organization
in the United States. It had become necessary that the
medical profession should be unified and separated from
those practising under sectarian designations, particularly
as at least one sect was beginning to secure the confidence
of men otherwise intelligent, and assumed to practise medi-
cine on a scientific basis. Nearly coincident with the or-
ganization of this Association was the discovery to which
I have already alluded, that marked a grand epoch in
the history of American medicine. On October 17, 1846,
practically the first surgical operation w'as performed un-
der the influence of an anesthetic administered by in-
halation. Its semicentennial has recently been impres-
sively celebrated at the IMassachusetts General Hospital,
in Boston. There are few who remember the horrors of
severe surgical operations and the agonies of dif^cult
■childbirth before anaesthesia, as there are few remaining
who participated in the convention which organized what
is now the American Medical Association; but all can real-
ize what surgery would be W'ithout artificial insensibility
to pain, and w^hat the medical profession would be without
a National Association.

The status of medicine forty years ago is quite within
my recollection. Medicine is not, never was and never
will be an exact science; but it always has been progres-
sive and never more so than at the present time. Fifty
years ago perhaps medicine merited the reproach of being
the least exact of all sciences; but its progress within the
last fifteen years has been so prodigious that it is now in
advance of them all. The Abbe illuminating apparatus

26o ANNIVERSARY ADDRESS

made the study of bacteria possible; and this, with the
wonderful apochromatic lenses, as it now appears to us,
have rendered nearly perfect our technical means of his-
tological and bacteriological research. We no longer dif-
ferentiate and separate structures by the coarse methods
of actual dissection alone; but with the delicate and pre-
cise instruments used in cutting thin sections and by stain-
ing we have come to an exact knowledge of physiological
and pathological histology, which, fifty years ago, seemed
unattainable. Without staining fluids, the physiological
and pathological histology of the present day would be
impossible. Fifty years ago skill in the diagnosis of cer-
tain diseases was acquired only by long practice and large
experience. With our present methods, properly em-
ployed, it is impossible to make an error in the diagnosis
of many of the diseases which formerly presented difficul-
ties, such as typhoid fever, tuberculosis, diphtheria, chol-
era and most of the neoplasms. To say that pathology
has been revolutionized within the last ten or fifteen years
is not enough — a new pathology has been created, and
with it have come an intelligent hygiene, prevention and
therapeutics, based upon exact scientific knowledge.

Eleven years ago the great physician whose name I
bear and who still lives in the memory of this Association
wrote an address which was to have been delivered before
the British Medical Association, entitled Medicine of the
Future. This classic legacy to the profession he so loved
and adorned embodied recollections of a half-century of
medical observation, with a prophetic view of the possibil-
ities of medicine within the succeeding half-century. It
was difificult for this wise physician to restrain his predic-
tions within the bounds of reasonable enthusiasm. The
epoch-making discovery of the bacillus tuberculosis, an-
nounced by Koch in 1882 and graphically described and
illustrated by Dr. Belfield before this Association, at the
meeting of 1883, made a most profound impression upon
his mind and imagination, which found expression in an
elaborate paper on the subject read in January, 1884. His
predictions of possibilities in medicine before 1936 are now
more than verified. It was predicted that " before the
lapse of another half-century there will be another era in
organic chemistry, and that light will penetrate dark re-

ANNIVERSARY ADDRESS 261

cesses which histology can not reach." If " Hght " be taken
in its Hteral sense, is not this more than realized by Ront-
gen's marvelous discovery, in which a hitherto unknown
light is made to penetrate opaque matter and disclose the
invisil)le! In 1886. he wrote: " Moreover, there are pres-
ent intimations of important discoveries respecting inocu-
lation W'ith attenuated viruses and contagia in order to
forestall the development of infectious diseases. Here
open up to the imagination the future triumphs of pre-
ventive medicine in respect to all classes of disease." Now,
little more than ten years later, serum-therapy has taken
a permanent place in practice, and we stand on the
threshold of a full knowledge of immunity, natural and ac-
quired.

As no human imagination fifty years ago could have
pictured the condition of the medicine of to-day, so it to-
day seems impossible to imagine its progress in another
half-century. Never, since medicine became a science, has
medical history been made so fast as now-. Between the
time of writing and of delivering this address, scientific
labor may give birth to a discovery destined to revolution-
ize some department of medicine, as Pasteur, Koch and
their follow^ers have revolutionized therapeutics, and as
Lister has created a new surgery.

The reasonable limits of an anniversary address do
not permit even an enumeration of the greatest of the
advances in the science of medicine since the organization
of this Association, much less their discussion. Your ora-
tor on surgery will find it impossible adequately to de-
scribe the progress of the last half-century in a single
address; your orator on state medicine can hardly com-
pass the wonderful advances made even in the single line
of prevention of disease; and I certainly can not hope to
be more successful.

It is a matter of congratulation that the name of this
body was early changed from National to " American
Medical Association." We have good reason to be proud
of American medicine, and our great representative asso-
ciation may properly claim a distinctive title. When one
is able to call up at random the discoveries in gastric di-
gestion, anesthesia in surgery and obstetrics, the success-
ful deligation of the arteria innominata, the operation for

262 ANNIVERSARY ADDRESS

vesico-vaginal fistula, o\-ariotomy and intestinal anasto-
mosis, to say nothing of minor advances in medicine and
surgery, can we not claim a distinctive place for American
medicine! It is in the United States that advances in the
science of medicine find the most ready acceptance and
appreciation. The American physician is the most intelli-
gent and judicious therapeutist; and in the United States
are the best and safest surgery and gynaecology.

I hope to see, beginning with the second half-century
of the American Medical Association, a more complete
unity of the profession, through its authority and influ-
ence. In the matter of general professional welfare, there
seems to me nothing more important than uniformity in
medical legislation, and. so far as possible, in educational
requirements preliminary to the study of medicine and
for license to practise after graduation. Admitting the
proposition that the profession is crowded, it is evident
that this condition is most serious in the large cities; but
overcrowding can not be prevented by legislative enact-
ment, except in so far as unqualified men are excluded.
Uniformity of legal qualifications to practise medicine in
the different States can best be secured by making every
State society actually, as well as nominally, a branch of the
American Medical Association, with permanent commit-
tees from each State organization together to constitute a
central legislative body. The object of this central body
should be to secure uniform medical laws in all the States,
making any State license valid for all, and a matriculation
certificate for one State good for matriculation in all
schools represented in the Association of American Medi-
cal Colleges. A certain kind of medical instruction must
be concentrated in large cities, where clinical material is
abundant; and absolute uniformity of curriculum can not
exist in all colleges; but certainly the legal requirements
for practice', as determined by examination by State
boards, can be made practically identical for all the States.
While this would not prevent ambitious young men from
trying their fortunes in large cities, it would distribute
well-qualified physicians more equally in the country at
large and tend to raise the standard of qualifications and
usefulness of the average country doctor.

It is the prerogative of the presiding officer of this

STERCORIN AND CHOLESTEREMIA 263

association to make recommendations, and this is not the
province of one appointed simply to give an anniversary-
discourse. At the jubilee meeting to be held later in the
session, it is hoped that the four sundving members of the
convention of 1846 will be present. From at least one
of these you may expect a more accurate and complete
account of the past work oi the association and a more
intelligent view of its probable future than I am able to
give. What I have had the honor to present I well know
is entirely inadequate to the occasion, and it has been
given merely as an introduction to addresses by others,
W'hich will be much more suitable and interesting. The
remainder of the time that has been placed at my disposal
I shall venture to occupy with a subject which I hope
may not prove entirely unworthy of your attention.

STERCORIN AND CHOLESTEREMIA

^^'hile the presentation, on this occasion, of researches
made and published thirty-five years ago (viewing the
question from a physiological standpoint) calls for an ex-
planation and perhaps an apology, none is required if their
great importance in relation to the pathology of the liver
is considered, especially as cholesteremia is by no means
accepted as a distinct pathological condition. Were it
not that stercorin has just been rediscovered in Germany
by two eminent physiological chemists, who make no men-
tion of its full description in 1862 and have even called
it by another name. I probably should not have repeated
and extended my original observations. As it is. how-
ever, I feel that I may properly, as an American investi-
gator, make my reclamation before the American ]\Iedical
Association. Although my paper, published in the " Amer-
ican Journal of the Medical Sciences " in October, 1862,
received an " honorable mention '' and substantial recog-
nition from the Institute of France and my observations
have been verified and extended by French and German in-
vestigators, many writers on physiology and pathology,
even the most recent, fail to recognize such a substance
as stercorin and in treating of cholesterin speak of its
function as obscure or unknown.* In " An American

* Foster, "A Text-Book of Physiolog)," New York and London, 1S95, p. 356

264 STERCORIN AND CHOLESTEREMIA

Text-Book of Physiology," Philadelphia, 1896, cholesterin
is described as a constant constituent of the bile, very wide-
ly distributed in the body and eliminated by the liver-cells
from the blood. " That it is an excretion is indicated by
the fact that it is eliminated unchanged in the feces."
Stercorin is not mentioned. As a matter of fact, choles-
terin does not occur in the human feces in health, and its
presence in this situation is exceptional.

In Hoppe-Seyler's " Zeitschrift fiir i)hysiologische Che-
mie," Strassburg, 1896, is a paper by Bondzynski and
Humnicki entitled " The Destination of Cholesterin in the
Animal Organism." The authors profess to have discov-
ered a new constituent of the human feces, which they
call " koprosterin." This substance is identical with ster-
corin, fully described in 1862. The reading of this article
led me to repeat the original researches of 1862, carrying
them out by the methods then employed, at the same time
repeating the observations of Bondzynski and Humnicki
with the methods and appliances used in their work. It
is mainly an account of these new observations that I now
give. The chemical manipulations were done by Dr. H.
A. Haubold, assistant to the chair of physiology in the
Bellevue Hospital Medical College, and J. A. Mandel, as-
sistant in the department of chemistry in the College of
the City of New York and to the chair of chemistry in
the Bellevue Hospital Medical College. To these two
skillful assistants I am indebted for most painstaking and
accurate work extending over a period of several months.

The original stercorin, of which specimens obtained in
1862 are in my possession, was extracted from the human
feces by the following process: The dried and pulverized
feces were extracted with ether. The ethereal extract was
passed through animal charcoal and afterward evaporated.
The residue was then extracted with boiling alcohol. The
alcoholic extract was treated with potassium hydrate solu-
tion, at a temperature near the boiling point of water, in
order to remove the fats by saponification, which were
washed out with water until the filtrate was neutral and
perfectly clear. The filter was dried, extracted with ether,
and the ethereal extract evaporated to dryness and ex-
tracted with boiling alcohol. The stercorin was obtained
from the alcoholic extract by repeated crystallization.

STERCORIN AND CHOLESTEREMIA 265

This process was exactly repeated in our recent ob-
servations, and at the same time stercorin was extracted
by the process described by Bondzynski and Humnicki.
Normal human feces were obtained to the amount of about
fifty pounds. After drying, the feces were divided. Two
analyses each were made by Haubold and Mandel, each
one extracting stercorin in one portion by the original
method, and in the other by the new method. All the
extracts obtained were identical in their composition, re-
actions and the form of crystals. It was fortunate that I
had for comparison a fairly large specimen of stercorin
extracted in 1862, and a microscopic slide bearing the date
of June, 1862, in which the crystals were perfect. The
product obtained by my process was a little more abundant
and crystalHzed rather more readily than that obtained
by the later method.

In the process employed by Bondzynski and Hum-
nicki, the dried feces were extracted with ether, using
Soxhlet's extraction-apparatus. The fats were saponified
with sodium alcoholate. No animal charcoal was used.
The substance was purified by repeated crystallizations.
These variations from the original method are unimpor-
tant, except in so far as they expedite the process of ex-
traction. The form of the crystals and the reactions were
identical with those which I obtained for stercorin in 1862.
Analyses of the products obtained by us, full details of
which are given in a paper sent to Hoppe-Seyler's " Zeit-
schrift," gave, for stercorin, the formula, C27H4SO, the
formula found for cholesterin being C27H46O. The change
of cholesterin into stercorin is effected by the addition
to the former of two atoms of hydrogen. A close com-
parison of the results of our ultimate analyses with those
obtained by Bondzynski and Humnicki shows conclusively
that *' koprosterin " and stercorin are identical, and that
stercorin is not an impure cholesterin, as is held by some
eminent investigators, such as Hoppe-Seyler, K. B. Hoff-
mann and others. Stercorin crystallizes in long, fine nee-
dles which radiate from a centre, forming tufts, and which
can not be confounded with the characteristic crystals of
cholesterin. In a chloroform solution, stercorin gives, with
an equal volume of concentrated sulphuric acid, first a
yellow color and then a gradual change to orange, red and
18

266 STERCORIN AND CHOLESTEREMIA

finally dark red. Treated in the same way, cholesterin
promptly gives a blood-red reaction without these inter-
mediate tints.

The o])inion expressed by Hoppe-Seyler, Hoffmann,
and indeed many others, that stercorin simply is impure
cholesterin, can not have been based upon a practical
knowledge of this substance. Stercorin has a well-defined
formula (C27H4f^O) which has been calculated and veri-
fied by the formation of esters. Its crystals are quite dif-
ferent from crystals of cholesterin and are invariable in
form, arrangement and color. It was extracted by meth-
ods practically the same as those used in the extraction
of cholesterin. In view of these facts, to assume that ster-
corin is an impure substance one must deny a positive sci-
entific basis to organic chemistry.

In the recent, as well as in the original observations
it was clearly shown that cholesterin is changed into
stercorin in passing down the intestinal canal. I found
that this change involves processes incidental to intes-
tinal digestion. Cholesterin and no stercorin was found
in the feces of fasting animals and in the meconium.
Bondzynski and Humnicki found an increased proportion
of " koprosterin " in human feces after the ingestion of
a certain quantity of cholesterin. They also showed that
cholesterin united readily with bromine, while " kopros-
terin " formed no such combination; and, indeed, by the
use of bromine, these two substances may be separated
when they exist together. They confirmed the empirical
formula for their product by the formation of a number
of esters.

In 1862 I wrote: "What the discovery of the func-
tion of urea has done for diseases which now come under
the head of uremia, the discovery of the function of cho-
lesterin may do for the obscure diseases which may here-
after be classed under the head of cholesteremia."

It is now generally admitted that the bile, in addition
to its function connected with digestion, contains one or
more excrementitious matters. Taking into consideration
the various ingredients of the bile, there seems to be but
one that can logically be compared to urea. Cholesterin
is found in many of the tissues and organs of the body
and exists in the blood. Likening it to urea, it becomes

STERCORIN AND CHOLESTEREMIA 267

a question whether it is formed in the liver and discharged
in the bile or is merely separated from the blood by the
liver and excreted. As it is constantly found in notable
quantity in the nervous tissue, in the proportion of eight
to twelve parts in a thousand, it occurred to me to ex-
amine the blood of the internal jugular and compare the
proportion of cholesterin with that found in arterial blood.
In one experiment on a dog, the blood being taken with-
out using an anesthetic, I found an increase in the jugular
over the carotid of nearly sixty per cent. In an etherized
animal the increase was only about three and a half per
cent. In another dog, not etherized, the increase was
about twenty-three per cent. There was also an increase
of four to six per cent, in the blood of the femoral vein
over arterial blood. In three cases of hemiplegia, the
blood from the arm of the sound side contained about the
normal proportion of cholesterin, while blood from the
affected side contained no cholesterin.

In an experiment on a dog it was found that the arterial
blood lost, about twenty-three per cent, and the portal
blood about four and a half per cent, in passing through
the liver, comparing these two kinds of blood with blood
taken from the hepatic vein.

These experiments led to an examination of the feces
to determine the quantity of cholesterin discharged; but
in a number of careful examinations of many different
specimens of feces I was unable to find cholesterin. I
found, however, what appeared to be a non-saponifiable
fatty substance in considerable quantity. Examining this
substance daily with the microscope, after five or six days
I saw crystals beginning to form, which finally presented
the appearances I have already described as characteris-
tic of stercorin. I found the daily discharge of stercorin
to be 0.7 gramme, about equal to the estimated quantity
of cholesterin discharged into the intestine in the bile in
the twenty-four hours. In but one examination of feces
of the dog did I find cholesterin, and this was in a fasting
animal, a small qviantity of cholesterin being found with
stercorin. In a specimen of meconium, I found a hundred
and sixty parts in a thousand, of cholesterin and no ster-
corin. In clay-colored feces from a patient with jaundice
from obstruction, neither cholesterin nor stercorin was

268 STERCORIN AND CHOLESTEREMIA

found. In the feces of the same patient, which were nor-
mal in color and obtained fifteen days after the first exam-
ination, stercorin was found and no cholesterin. These
experimental facts seemed to show that the stercorin of
the feces was derived from the cholesterin of the bile,
and that the change of cholesterin into stercorin was in-
cidental to the processes of intestinal digestion. In no
case was I able to detect in the feces any trace of the
biliary salts.

Passing from these observations to the pathological re-
lations of cholesterin, after examining three specimens of
normal blood and finding the proportion of cholesterin
to be 0.445 to 0-75I o^ ^ P^^^ i^ ^ thousand, examinations
were made of the blood of patients with simple jaundice
and those with what is called icterus gravis the cases ter-
minating fatally with grave nervous symptoms. In a case
of sim])le jaundice terminating in recovery at the end of
about four weeks, the blood contained 0.508 of a part in
a thousand, well within the limits for normal blood. In
a case of jaundice with cirrhosis terminating fatally with
serious nervous disturbance, the blood taken six days be-
fore death contained 1.850 part in a thousand, of choles-
terin, an immense increase over the normal proportion.
In this case, on post-mortem examination, the liver was
found contracted, and the gall-l3lad(ler was shrunken con-
taining only about seven cubic centimetres of bile.

The question of cholesteremia has been much discussed
since 1862, in great part with scant approval or with-
out acceptance. However, Picot,* in 1872, reported a
fatal case of " grave jaundice " in which he determined
a great increase in the proportion of cholesterin in the
blood, 1.804 part in a thousand. Many attempts have
been made, also, to produce toxic effects by injecting cho-
lesterin into the blood, but most of them have been un-
successful on account of mechanical obstruction of the
blood-vessels. In 1873, however, Koloman Miiller f suc-
ceeded by injecting cholesterin rubbed with glycerin and
mixed with soap and water. In five experiments on dogs,
injecting in each 0.045 gramme of cholesterin, he pro-

* "Journal de I'anatomie," Paris, 1872, tome viii, p. 246 et seq.
f Ueber Cholesteramie, " Arcbiv flir experimentelle Pathologic und Phar-
makologie," Leipzig, 1873, Bd. i., S. 213 et seq.

STERCORIN AND CHOLESTEREMIA 269

duced a " complete picture of the symptoms of grave
jaundice."

In repeating the original researches of 1862, the ob-
servations, as regards analysis of feces, etc., were some-
what extended. With modern apparatus, the manipula-
tions may be freed from many disagreeable features which
heretofore, probably, have interfered with this line of in-
vestigation. In extracting stercorin, various volatile fatty
acids and other substances were removed, the constitu-
tion and relations of which are unknown. \Ye studied, in
this connection, some of the products of bacterial action,
obtaining, by the action of fecal bacteria on proteids, ska-
tol and indol. both substances containing nitrogen. It is
well known that phenol and cresol also exist in the feces.
These nitrogenous matters are putrefactive products;
nothing is known of their physiological or pathological
relations, and up to this time stercorin is the only excre-
mentitious matter yet found in the feces, the origin and re-
lations of which are at all understood. Our knowledge,
indeed, of the physiological chemistry of the feces is only
just begun; and we may look to future investigations for
much that will be most important as well as interesting.
The same may be said, in a measure, of the bile and of the
true pathology of certain functional and structural diseases
of the liver. How long shall we continue to speak of
biliousness, congestion or torpor of the liver, the classic
liver-complaint, " et id genus omne," using terms which
have no scientific meaning! Undoubtedly there are gen-
eral disturbances, dependent upon some disorder in the
functions of the liver, which occur without jaundice, and
this fact has long been recognized. In a case of cirrhosis
with considerable constitutional disturbance but no jaun-
dice, the blood was found to contain an excess of choles-
terin, 0.922 of a part in a thousand. In what is termed
acholia, there may be grave nervous symptoms without
jaundice, and the pathology of such cases is unknown. The
biliary salts are not found in the blood, and the symptoms
can not be accounted for by disturbances in digestion. It
is possible that light will be thrown on their pathology if it
is admitted that there is a condition called cholesteremia.
As yet this is but speculation; but if the theory of choles-
teremia is accepted, a wide field of inquiry is opened in this

270 STERCORIN AND CHOLESTEREMIA

direction, and ere long we may speak of " biliousness " and
" liver complaint " with some definite ideas of their pa-
thology.

It must be remembered that the liver is by far the
largest gland in the body; that it secretes a fluid which is
known to have a double function, one connected with di-
gestion and the other with the elimination of cholesterin;
that the blood from the digestive tract all passes through
this organ, where it undergoes certain changes; that it
probably stores up the products of amylolytic digestion in
the form of glycogen; that it arrests certain poisons, and
that it is the chief organ concerned in the production of
urea, which is discharged by the kidneys. It may have
other uses in what is now called internal secretion, in ad-
dition to that of destruction of blood-corpuscles and the
change of hemoglobin into bilirubin. With all these
known varied uses of the liver, however, the pathology
of hepatic diseases is most obscure. We do not know,
even, the cause and mechanism of the formation of gall-
stones, which are often composed almost entirely of cho-
lesterin.

The term acholia, as used in pathology, now means
very little and conveys no distinct idea of the causes of
the nervous symptoms which attend this condition. The
term cholemia is generally regarded as almost synonymous
with jaundice. If cholesteremia is recognized as a distinct
pathological condition, with symptoms due either to the
accumulation of cholesterin in the blood, acting as a toxic
substance, or to imperfect separation of cholesterin from
the nervous tissue, a positive advance will be made in our
knowledge of the pathology of many obscure liver dis-
orders.

The quantitative estimation of cholesterin in the blood
is not difficult, and it does not require more than four to
six or eight grammes of blood. The only tedious ma-
nipulations are the drying, saponification and weighing;
and these are readily done in a well-appointed laboratory.
Some process may be devised which will expedite this ex-
traction. If examinations of the blood were to be made
in cases of obscure nervous disturbance, in epilepsy and
other disorders of this nature, it is possible that cholesterin
may be found to play an important part in their pathology.

Fig. 3. — Stcrcurin, U. and II., 1897.

fiG. 4. — Stercorin, Flint, 1862, recrystallized Fig. 5. — Stercorin, Flint, original slide
in 1S97. of 1S62.

Photographs by Prof. E. K. Dunham, M. D. All magnified twenty diameters.

STERCORIN AND CHOLESTEREMIA 271

The fact that bromine readily combines with cholesterin,
taken in connection with the wide use of the bromides in
diseases of the nervous system, is very suggestive. May
not the bromides promote the ehmination of cholesterin,
a substance which is so insoluble and which forms few com-
binations! These points seem well worthy of the consid-
eration of pathologists and therapeutists. Certainly the
physiological and pathological relations of cholesterin offer
a wide and perhaps fruitful field for further observation.

With this paper I present photographs of cholesterin,
stercorin extracted by the original method, and stercorin
extracted by the method of Bondzynski and Humnicki,
all in 1897, with a photograph of crystals obtained in 1897
from a specimen of stercorin extracted in 1862.

I have added, for comparison with the recent crystal-
lization from the specimen of 1862, a photograph from a
slide marked June, 1862. These crystals, which are from
the same specimen of 1862, have been mounted for thirty-
five years and are much more abundant and beautiful than
those obtained by recrystallization in 1897.

XII

UEBER STERCORIN

(Aus dem physiologischen Laboratorium des Bellevue Hospital Medical
Colle^je der Stadt Nevv-Vork. Der Redaction zugegangen am 3. Juni, 1897.)

Published in Hoppe-Seyler's " Zeitschrift fiir piiysiologische Chemie,"^
August 28, 1897.

In Folge einer Mittheilung der Herren Bondzynski
und Humnicki " Ueber das Schicksal des Cholesterins im
thierischen Org-anismus " in Band XXII, Seite 396-41Q
dieser Zeitschrift, sehe ich mich veranlasst, aufs Neue auf
meine Beobachtungen iiber Stercorin aufmerksam zu ma-
chen.

Die Herren Bondzynski und Humnicki Ijeschreiben
unter dem Namen K o p r o s t e r i n einen neuen Be-
standtheil der menschlichen Faeces. Diese Substanz ist
identisch mit dem von mir im Jahre 1862 entdeckten und
beschriebenen Stercorin. Da die genannten Autoren
zur Darstellung des Koprosterins dieselben Processe ange-
wandt und zu denselben Resultaten gelangt sind wie ich^
so erscheint es mir angebracht, meine friiheren Arbeiten im
Vergleich mit den Versuchen von Bondzynski und Hum-
nicki zu besprechen.

Beim Lesen der Arbeit von Bondzynski und Humnicki
erscheint es, als ob dieselben glauben. eine neue Substanz
im Koprosterin entdeckt zu haben. Es wird des Stercorins
und seines Entdeckers keine Erwahnung gethan, obgleich
das zuerst von mir beschriebene Stercorin in der deutschen,
franzosischen und englischen Literatur seit 1862 in mehr
oder weniger vollstandigen Berichten iiber dessen Eigen-
schaften und seine Beziehungen zum Organismus erwahnt
wird.

Meine Originalmittheilung wurde im Jahre 1862 im
" American Journal of the Medical Sciences " in Philadel-
phia veroffentlicht unter dem Titel " Experimental Re-
searches into a new Excretory Function of the Liver.'^
272

UEBER STERCORIN 273

Diese Function besteht in der Abgabe von Cholesterin aus
dem Blut und seiner Ausscheidung aus dem Korper in der
Form von Stercorin. Im Jahre 1868 wurde von G. Bailliere
in Paris eine Uebersetzung ins Franzosische veroffentlicht,
und im Jahre 1869 erhielt das Werk bei der Bewerbung
um den Preis, der Villemins Arbeit iiber die Contagiositat
der Tuberculosis zuerkannt wurde, eine " ehrenvolle Er-
wahnung " und eine Belohnung von 1500 Francs vom In-
stitut de France. Seit der Zeit sind ausfiihrliche Berichte
liber Stercorin erschienen in einem meiner Vortrage, ver-
offentlicht in den " Transactions of the International Med-
ical Congress," Philadelphia 1876, in meinem Werke
" Physiology of Man " in 5 Banden und in meinem Hand-
buch " Human Physiology," von welchem allein mehr als
20,000 Exemplare verbreitet worden sind; kurze Erwah-
nungen findet man fast in alien medicinischen Lexika und
in Werken iiber Pathologie, Physiologie und medicinische
Chemie. Die Anerkennung, die den griindlichen und ex-
acten Untersuchungen von Herren Bondzynski und Hum-
nicki gezollt werden muss, kann nicht auch auf deren Be-
kanntschaft mit der Literatur des Gegenstandes ihrer For-
schungen ausgedehnt werden. Ware es anders, so wiirde
ich nicht gezwungen sein, das Recht eines ersten Beobach-
ters auszuiiben, nach welchem ich Prioritat beanspruche
und fordere, dass der Name " Koprosterin " durch " Ster-
corin " ersetzt werde.

Das urspri^ingliche Stercorin, von welchem ich
Praparate in meinem Besitz habe, wurde durch folgenden
Process aus menschlichem Koth gewonnen.

Die getrockneten und pulverisirten Faeces wurden mit
Aether extrahirt. Das atherische Extract wurde durch
Thierkohle entfarbt und dann verdunstet. Der Ritckstand
wurde darauf mit kochendem Alkohol ausgezogen, das
alkoholische Extract mit einer Kalihydratlosung bei einer
etwas unter dem Siedepunkt des Wassers liegenden Tem-
peratur verseift, zur Entfernung der Seifen mit Wasser
gewaschen, bis das Filtrat neutral und vollkommen klar
war. Das Filter wurde dann getrocknet, mit Aether aus-
gezogen, das atherische Extract zur Trockne verdampft
und mit kochendem Alkohol extrahirt. Das Stercorin
wurde aus dem verdunsteten alkoholischen Extract durch
wiederholte Krystallisation aus Alkohol gewonnen.

274 UEBER STERCORIN

Dieser Process wurcle' audi bei clcn ncucn Versiichen
wiederholt und das erhaltene Produkt ergab bei der Ele-
mentar-Analyse die folgenden Resultate:

Nr. I. Substanz 0,2781 gr.; €02:0,8521 gr., H2O: 0,3064 gr.
Nr. II. „ 0,2437 „ „ 0,7461 „ „ 0,2701 „

entsprechend

Nr. I Nr. 2

Kohlenstoff 83,56^ 83,49^

Wasserstoff 12,245^ 12,31^

wahrend Bondzynski und liumnicki das Folgende fiir ihr
" Koprosterin " fanden:

1. Substanz 0,3242 gr., €02:0,9908 gr., H2O : 0,3595 g^-

2. „ 0,2954 „ „ 0,9035 „ „ 0,3255 „

3. „ 0,2684 " " 0,8224 „ „ 0,2968 „

entsprechend

I.

Kohlenstoff 83,24
Wasserstoff 12,24

83.41
12,24

83^56
12,21

Beim Vergleichen dieser beiden Reihen von Resultaten
ist es ersichtlich, dass die nach meiner Originalmethode
isolirte Substanz mit Koprosterin identisch ist.

Stercorin krystallisirt in langen, feinen Nadeln, die von
einem Centrum ausstrahlen und Biischel bilden, und diese
Krystalle konnen gar nicht mit Cholesterinkrystallen ver-
wechselt vverden, wie von einigen Forschern, wie Hoppe-
Seyler, K. B. Hoffmann u. a., behauptet worden ist.

Die Reactionen des Stercorins sind mit denen des " Ko-
prosterins " identisch, in Chloroformlosung gibt es nam-
lich mit einem gleichen Volumen cone. Schwefelsaure
zuerst eine gelbe Farbe, welche beim Stehen sich langsam
in eine orangerothe und dann in dunkelrothe Farbe um-
wandelt.

Liebermanns Reaction gibt mit einer Chloroformlo-
sung von Stercorin sofort eine blaue Farbe, die bald von
einer griinen gefolgt wird.

In dem von Bondzynski und Humnicki angewandten
Process wurden die getrockneten Faeces vermittelst Soxh-
lets Extractionsapparat mit Aether extrahirt, Die Fette
wurden mit Natriumalkoholat verseift. Thierkohle wurde
nicht angewendet, sondern die Substanz wurde durch wie-
derholte Krystallisation gereinigt. Diese Abweichungen

UEBER STERCORIN 275

von meiner urspriinglichen Methode sind unwesentlich, sie
beschleunigen nur den Extractionsprocess. Das nach
dieser Methode erhaltene Produkt ist sowohl beziiglich
der Krystallform wie auch der chemischen Eigenschaften
mit Stercorin identisch. Die Feststellung dieser That-
sachen ist geniigend und es ist iiberfliissig, der ausserst
sorgsamen Arbeit der Herren Bondzynski und Humnicki
Weiteres hinzuzufiigen.

In meinen neuen, ebenso wie in den friiheren urspriing-
lichen Beobachtungen, habe ich klar nachgewiesen, dass
Cholesterin beim Durchgang durch den Darmkanal in
Stercorin umgewandelt wird. Ich fand, dass diese Veran-
derung auf den Processen der Darmverdauung beruht.
Cholesterin und kein Stercorin wurde in dem Koth von
fastenden Thieren und im Meconium gefunden. Bond-
zynski und Humnicki fanden nach Einnahme einer be-
stimmten Alenge Cholesterin eine vermehrte Menge Ko-
prosterin in den menschlichen Faeces.

Diese Forscher berechneten die Formel Co-H4gO fiir
" Koprosterin " und Co-j^i^^O als Formel fiir Cholesterin.
Hieraus ergibt sich, dass die Veranderung des Choleste-
rins in " Koprosterin " auf dem Eintritt von zwei Atomen
Wasserstofif beruht. Sie zeigten auch, dass das " Kopro-
sterin " keine Verbindungen mit Brom bildet, wie dies
beim Cholesterin der Fall ist. Durch Brom konnen auch
diese beiden Substanzen getrennt werden, wenn sie zusam-
men vorkommen.

Die Beobachtungen von Bondzynski und Humnicki
w'aren rein chemischer Natur. In meiner Originalarbeit
untersuchte ich zunachst die physiologischen Eigenschaf-
ten und Beziehungen der Galle in ihrer Bedeutung sowohl
fiir die Verdauung und Resorption als auch fiir die Excre-
tion. Ich studirte dann das Cholesterin, wie es in gewissen
Organen, Geweben und Fliissigkeiten des Korpers gefun-
den wird. Ich zeigte, dass die Menge des Cholesterins im
Blute vermehrt wird bei dem Durchgang des letzteren
durch das Gehirn und verhaltnissmassig verringert wird
beim Durchgang durch die Leber, und wies nach, dass
Cholesterin, wenn es ein Ausscheidungsprodukt ist, w^ahr-
scheinlich zum grossten Theil das Resultat von Umsetzun-
gen im Nervengewebe ist.

Dann zeisite ich die Verwandlunsf des Cholesterins im

276 UEBER STERCORIN

Diinndarm unci entdeckte Stercorin in den Faeces in einer
Quantitiit, die der Menge des in der Galle ausgeschiedenen
Cholesterins fast gleich kam.

Eine Entschuldigung dieses Prioritatsansprtichs auf die
Entdeckung des Stercorins als eines Bestandtheils der
Faeces tind dieses Protestes gegen den Namen " Kopro-
sterin " mag aiis der hohen Wichtigkeit der Beziehung
dieser Siibstanz ziim Cholesterin und aus der grossen Be-
deiitung des von mir als Cholesteraemie bezeichneten
Krankheitszustandes hergeleitet werden.

Ich bin weit davon entfernt, irgend einen Vorwiirf ge-
gen die Herren Bondzynski und Humnicki zu beabsichti-
gen, ich bin ihnen sogar zu Dank verpflichtet, da ihre von
den meinen unabhangigen Beobachtungen wahrscheinlich
veranlassen werden, dass die Existenz des Stercorins und
der Cholesteraemietheorie die allgemeine Anerkennung
findet, auf welche ich, mit wenig oder gar keiner Ermuthi-
gung, 35 Jahre gewartet habe.

Zu gleicher Zeit nehme ich Veranlassung, meinen As-
sistenten, den Herren H. A. Haubold und J. A. Mandel,
meinen Dank auszusprechen fiir ihre gewissenhaften und
anerkennenswerthen Arbeiten bei der Wiederholung der
urspriinglichen Darstellung des Stercorins.

XIII

ON THE ORGANIC NITROGENOUS PRINCIPLES
OF THE BODY WITH A NEW METHOD FOR
THEIR ESTIMATION IN THE BLOOD

PART I

Published in the " American Journal of the Medical Sciences "
for October, 1863.

Composition and Properties of the Organic
Nitrogenous Principles of the Body. — The physi-
ological investigator of the present day is greatly depend-
ent upon chemistry for methods of investigating the func-
tions of the body; so much so, indeed, that these depart-
ments can not be separated from each other; and it is to
physiological chemistry he must look for the solution of
questions of the highest importance which yet remain
unanswered. Of the various questions which thus re-
main to be answered by the chemist, that of the quantity,
composition, condition of existence and changes of the
organic nitrogenous principles is the most important; for
these apparently are the constituents of the body endowed
with vital properties; they regulate the changes which take
place in the other principles, and the various modifications
which they undergo in the body constitute the mysterious
'' life," the comprehension of which has not yet been grant-
ed to the student of Nature. Though chemistr}^ has en-
abled the physiologist to make but little if any progress
toward the solution of the great question of vitality, it has
helped him to comprehend certain of the phenomena of
living bodies; and by long searching he has found out some
of the laws which regulate their phenomena. The results
of the physiological labors of centuries have only confirmed
an axiom which must be recognized by every one who
hopes to make any advance in this science.

The laws which regulate animated Nature are irrevo-

277

278 ORGANIC NITROGENOUS PRINCIPLES

Ccibly fixed; as distinct from those which g-overn inanimate
objects as life is from death. They must be sought for by
a patient study of the phenomena of Hfe, until the chain
of evidence is complete. The mind must seek to compre-
hend, not to create.

Much ineffectual labor has resulted from a lack of com-
prehension of this idea. While physiology was com-
paratively new as a science, many endeavored to establish
laws for the regulation of the economy instead of add-
ing to actual knowledge of phenomena; and others,
ignorant of the fact that what is true of inanimate matter
can not be applied to the Hving body, endeavored to explain
everything by physical or chemical laws. To this latter
may be attributed the want of application of chemistry to
physiology until within the last few years; though, in all
ages, when learning has been cultivated, chemistry has
been a favorite study. Those who took such pride in the
discovery of elements and the establishment of physical
laws could not bring themselves to admit, and can not at
the present day admit that the body is anything but a col-
lection of elements regulated by the laws with which they
are familiar; while those who saw these laws so often
violated in living bodies were disposed to reject entirely
chemical and physical explanations of physiological phe-
nomena. To make use of chemistry, from which physi-
ology had so much to expect, it was necessary to cre-
ate a new method of study which would have reference to
organic substances and to substances not necessarily chem-
ical elements but formed from these elements, which are
now called proximate principles. It will be seen at once
how important are these principles with reference to their
condition and behavior in the living^ body, and how neces-
sary it is to study them from this point of view and not
sim.ply as inorganic or inanimate compounds.

There is thus a manifest difference between proximate
principles and chemical elements. The former have certain
properties in the living body which are different from any
known in the inorganic world. They may have properties
peculiar to animal substances, like albumin or myosin,
which are endowed in living bodies with the vital properties
of continual destruction and reparation; or the substance
may be inorganic, as water or chloride of sodium, but actu-

ORGANIC NITROGENOUS PRINCIPLES 279

ally entering into the composition of organized tissues and
participating in the peculiar changes which they undergo.
The latter are indivisible substances, possessing no power
of self-regeneration, forming definite compounds by union
with other elements of the same class, by which union the
properties of the component parts are radically changed.
Chemical elements can be studied, and have been studied
for years, without reference to organized or living struc-
tures; though these are formed necessarily of such ele-
ments, and as such have been found to possess certain
definite properties. When the chemist, in investigating
organic bodies, studies only the ultimate elements of which
they are composed, he learns nothing more of the proper-
ties of these elements, for they are identical with those he
extracts from inorganic substances. He gives simply the
results of decomposition of the body; but w^iat the physi-
ologist wishes to know is the function of the systems
and organs and the elements which compose the tissues of
the body. The viltimate composition of organic bodies is
manifestly of little importance compared with a knowledge
of their physiological properties; unless, indeed, this should
explain their function, a hope of the chemist which is rarely
realized. Thus the body can not advantageously be studied
from a purely chemical point of view; and the changes
which take place, even in its inorganic constituents, can
not be explained by formulas which indicate simply the
addition or subtraction of certain elements. Within a few
years a great advance has been made in physiological chem-
istry by a modification of the method of study of organic
matters. The most rational investigators of the present
day treat them as compound substances, which can not be
decomposed without destroying their peculiar properties.
But a still further advance is necessar}': they must be con-
sidered, not merely as proximate principles, which can be
separated from the body by means which do not interfere
with their chemical composition, but as principles capable
of performing their functions only when united together,
as they certainly are in Nature. For example, what has
been considered as albumin, that is, dried albumin, is in-
capable of performing its function if it is not united w'ith
water, chloride of sodium and other inorganic substances
which are always found in connection with it; and though

28o ORGANIC NITROGENOUS PRINCIPLES

it is important to know its ultimate composition and its
behavior on the application of heat, in the presence of acids,
etc., etc., these phenomena are artificial and useful only
as tests. The true line of incjuiry lies in a study of its be-
havior in the body and the investigation of natural, rather
than artificial phenomena. Instead of attempting to isolate
it completely, it should rather be studied in its union with
the other principles by which it is enabled to perform its
functions; and when it is separated from the animal fluids
in order to ascertain its proportional quantity, it should be
separated with those other substances which are united
with it in the living body and without which it can per-
form no vital functions. It will be seen that some of these
substances, as water, actually enter into the composition
of the organic principles and can not be separated without
alteration and decomposition.

These preliminary remarks explain why I consider it
of the greatest importance to study, first of all, the condi-
tion under which organic substances exist in the body, espe-
cially as this question is almost ignored by physiologists.
To correspond with the ideas I shall present upon this
question, a new method of estimating the quantities of
these substances is necessary, as the ordinary analyses are
the work of chemists who have not appreciated their con-
dition of existence. In discussing this question I shall re-
view to some extent the opinions and analyses of chem-
ists, which are accepted at the present time.

Ultimate Composition of Organic Nitrogenous
Substances. — According to the present views, every
tissue of the body and all the fluids, with the exception
of the excrementitious fluids, contain a characteristic ele-
ment, which is found in no other situation and which
gives certain properties connected with nutrition, which
may be called vital. These tissues and organized fluids
contain usually but one characteristic organic principle.
With the exceptions of the blood and milk, there is but
one such element to each tissue or fluid. The blood, how-
ever, which furnishes the material for the formation of
all these substances, contains several organic principles;
viz., fibrin, albumin, and globulin; and the milk contains,
in addition to casein, a trace of albumin. Although it is
probable that all the tissues and organized fluids (excre-

ORGANIC NITROGENOUS PRINCIPLES 281

mentitious fluids excepted) contain principles of this kind,
whicli are characteristic and present shades of difference for
each one, some have not yet been separated sufficiently
for purposes of study; and according to Robin and Verdeil,
only seventeen can be regarded as well established.*

LIST OF ORGANIC NITROGENOUS SUBSTANCES
Name. Where found.

Fibrin Blood, chyle, lymph.

Albumin Blood, chyle, lymph, serum, milk.

Albuminose Chyme, blood.

Casein Milk.

Mucosine Mucus.

Pancreatine Pancreatic juice.

Globuline Blood-globules.

Musculine Muscles.

Osteine Bone.

Cartilageine Cartilage.

Elasticine Elastic tissue.

Keratine Nails, hair, epidermis.

Crystalline Crystalline lens.

f Hematine Coloring matter of the blood.

, J Biliverdine " " " bile.

' ] Urosacine " " " urine.

1^ Melanine " " " pigment.

Of the seventeen principles above enumerated, only
three have been studied with any degree of accuracy; name-
ly, fibrin, albumin and casein. The proportion of these
principles in the fluids in which they have been found has
been carefully estimated; and in addition much pains has
been bestowed upon their ultimate analysis. Albumin has
given the name to nearly all these substances, from simi-
larity, as far as known, of composition, and the others, called
albuminoids, have been simply indicated in the situations
above enumerated, no attempt having been made, with
one or two unimportant exceptions, to estimate their quan-
tity or to ascertain their ultimate composition. In fine, the
blood and the milk are about the only fluids of the body
which have been subjected to critical analysis for organic
substances, and hardly anything has been done with the
solids. I do not propose in this article to take up the
chemistry of the milk; and throwing out this fluid, I am
reduced in my examination of analyses to the organic prin-

* " Traite de chimie anatomique," Paris, 1853.

+ These are simply coloring matters and are put by Robin and Verdeil in
this class as they contain nitrogen.

19

282 ORGANIC NITROGENOUS PRINCIPLES

ciples of the blood, which have justly claimed the most
careful investigation at the hands of physiological chemists.
In the latter part of the last century Bertholet demon-
strated the existence of nitrogen in organic bodies. Before
his time chemists had little idea of their composition. It
was known that they were very unstable, and the discovery
of the al)Ove-named ingredient offered a supposed explana-
tion of this fact; viz.. that its presence engendered a num-
ber of " attractions " which did not operate in bodies of a
less complicated composition. This discovery was a great
advance in the chemical knowledge of organic substances
of this class; and the researches of investigators since that
time have so far established it, that they are known gener-
ally under the name of nitrogenous, or azotized principles.
The organic matters were afterward closely studied by Du-
mas, especially those existing in the blood; and, indeed, the
mode of analysis of this fluid for its organic constituents,
employed by Dumas forty years ago, is the one adopted,
with but slight modifications, by chemists of the present
day. He ascertained, in the first place, the quantity of
water which could be driven ofT from the blood, and attrib-
uted it all to the serum, considering the fibrin and albu-
min as held in solution by this water and the globules as
possessing no fiuid of their own. By appropriate means,
which will be considered hereafter, he separated the fibrin,
albumin and glol)ules, evaporated them to dryness and esti-
mated them in this condition. The ultimate composition
of these principles was not then definitely ascertained; and
no theory of the mode of union, of their elements or their
formation was proposed. A few years later (1837), in con-
nection with Liebig, Dumas proposed a division of chem-
ical science into inorganic, or mineral, and organic. Ac-
cording to the theory proposed, all inorganic bodies were
composed of two elements directly combined, forming
what they called binary compounds, which again united
with other compounds formed in the same way. Thus,
potassium and oxygen united to form potash (KO), which,
in its turn, can unite with another binary compound, as
nitric acid (NO5), to form nitrate of potash (KO.NO5);
the elements first uniting together to form pairs, which in
their turn unite with each other. In inorganic chemistry
the union of elements proceeds in this simple manner to

ORGANIC NITROGENOUS PRINCIPLES 283

form the most complex substances; an element can unite
only with an element, a binary compound, with a binary
compound, and so on. Organic, particularly vegetable sub-
stances, on the contrary, were theoretically reduced to the
compounds of a radicle which, though itself a compound,
behaved toward elementary substances in the same way
as a simple inorganic element. In other words, the beha-
vior of these so-called organic radicles in their union wdth
elementary substances would lead one to suppose them to
be elements themselves; it is only chemical analysis which
shows them to be compound. For example, cyanogen will
unite with hydrogen to form hydrocyanic acid (HCy), as
chlorine will unite w-ith hydrogen forming hydrochloric acid
(HCl). The latter is an inorganic or mineral acid, and the
chlorine, which is the radicle, is of necessity an elementary
substance; but cyanogen, the radicle of the organic acid,
though it unites with the element hydrogen in the same
way as the chlorine, behaving like an elementary substance,
is found by chemical analysis to be a compound of carbon
and nitrogen (CN). It is in reality a radicle, but com-
pound; and a compound radicle is a thing unknown in
inorganic chemistry. The example just given shows a
marked difference in the behavior of inorganic and organic
substances, as the radicle CN, or cyanogen, actually ex-
ists and conducts itself, not as a compound, but as an ele-
mentary substance ; and if all organic compounds could
be shown to be formed of compound radicles, this would
constitute a true distinction between inorganic and or-
ganic combinations. But this is not the case; though
some chemists have theoretically reduced alcohol, ether,
acetic acid, and in fact all organic vegetable compounds,
to a union of elements with compound radicles, these
radicles, unlike cyanogen, are hypothetical. It is said,
for example, that the radicle ethyl (C2H5) unites with oxy-
gen to form the oxide of ethyl (€2115)20), which is ether;
but ethyl never exists in nature and can not be manufac-
tured. The same is true of the radicles, methyl, acetyl,
benzyl, ammonium, etc. The hypothetical character of
these radicles is universally acknowledged,* and the theory

* For a summary of the history of these so-called organic radicles the reader
is referred to a lecture by M. Auguste Cahours, published by the " Societe
chimique de Paris," 1S60, p. 51.

284 ORGANIC NITROGENOUS PRINCIPLES

of compound organic radicles, although it may serve to
exi)lain the composition of certain classes of organic
bodies, is not universally received by chemists of the pres-
ent day; it is rather a mathematical analysis than an
actual investigation of real substances; for with the ex-
ception of one or two, all these radicles are hypothetical.
This wholesale assumption of imaginary substances vio-
lates, in toto, the axiom enunciated at the beginning
of this article. Instead of studying the behavior of or-
ganic bodies, phenomena are imagined and facts distorted
to correspond with laws which are known to regulate
the behavior of inorganic substances. But it is beyond
the scope of this paper to treat of these purely chemical
questions; and the reason the theory of organic radicles
has been discussed at all is that it was followed the next
year (1838) by the theory of Mulder, by which he at-
tempted to explain the constitution of the albuminoids.
He supposed all organic nitrogenous substances in the
body to be formed by the union of certain elements with
a radicle, protein, giving to them the name of protein com-
pounds. This hypothesis was adopted by Liebig, Dumas
and Simon and is now accepted by many physiologists.

Protein. — x^s before remarked, the only albuminoids
that have been carefully studied are fibrin, albumin and
casein. In addition to a great similarity in the general
properties of these substances, ultimate analysis has shown
a remarkable likeness in chemical composition. It is not
to be wondered at, then, that an attempt should be made
to reduce all the compounds of this class to a series derived
from a common radicle, following upon the theory of or-
ganic vegetable radicles. This was done by Mulder; who,
treating albumin, fibrin or casein with alcohol and ether to
remove fats and with hydrochloric acid to remove inorganic
salts, dissolved these matters, thus purified, in a solution
of potash and precipitated by acetic acid a substance said
to possess always the same characters, which he called the
radicle of the albuminoids, and which, by union with a cer-
tain quantity of sulphur and phosphorus, was capable of
forming fibrin, albumin or casein. This, which is merely
an extension of the theory of compound organic radicles
into animal chemistry, has a more plausible basis than in
the case of vegetable organic compounds. The supposed

ORGANIC NITROGENOUS PRINCIPLES 285

radicle, protein, was obtained and analyzed by Mulder; and
if it could be definitely established to be the same for the
various substances from which it is extracted, and if these
substances could be shown to consist always of this radicle
with a definite proportion of sulphur or sulphur and phos-
phorus, the theory would be sustained so far as possible
with present means of investigation. It is true it would
be sustained only by analysis; but synthesis has not yet
been applied to animal chemistry. But the protein theory
is not susceptible of analytical demonstration. The com-
position of protein itself is not definitely settled; and a re-
view of the methods of ultimate organic analysis will show
that the varied results obtained by chemists do not depend
on a want of accurate means of analysis but upon the in-
definite characters of the compounds themselves. Take,
for example, the analyses of Mulder * showing the com-
position of the protein groups, and compare them with the
results obtained by other chemists!

Mulder gives the following formulas for the protein
group:

C40H31N6O12 = Protein.

C4oH3iN50ia + SPhj = Fibrin and the albumin of white of egg.

C40H31N6O12 4- SnPhi = Albunnin of serum.

C40H31N5O12 + S = Casein.

These analyses by Mulder have been confirmed by
Schroder and Von Laer.f

Regnault gives as the constitution of protein CseHo,-
N,0,o;t Sheerer, Q.H^.Ni.Ox.; * Liebig, C^HsoNeO^;
and Dumas, C4sH33N0O17.ll

The composition of fibrin, albumin and casein, given by
Dalton and credited to Liebig, is as follows:'^

Fibrin = C298H228N4o092S2

Albumin = CoisHiegNovOeeSa
Casein =: CaesHassNseOsoSa

* Robin and Verdeil, " Chimie anatomique," tome i., p. 652.

f" Animal Chemistry with reference to the Physiology and Pathology of
Man." By Dr. J. Franz Simon. Philadelphia, 1846.

X " Cours elementaire de chimie," etc. Par M. V. Regnault. Paris, 1853,
tome iv., p. 114.

* Milne Edwards, " Le9ons sur la physiologie," etc. Paris, 1857, tome i.,
p. 151.

II Robin and Verdeil, o/>. cit., tome i., p. 651.

^ Dalton, " Treatise on Human Physiology'." Second edition. Phila-
delphia, 1861, p. 80 ; and Robin and Verdeil, op. cit., tome iii., p. 147.

286 ORGANIC NITROGENOUS PRINCIPLES

Denis, in a paper presented to the Academy of Sciences
at Paris in 1839. advanced the view that fibrin and allnmiin
are identical in composition; and this view was sustained
by Liebig in a note to the Academy in 1841.*

With this diversity of opinion among chemists, based
on actual analyses, it is difficult to come to any conclusion
other than the following:

There is no evidence that fibrin, albumin and casein
are formed by the union of a definite proportion of phos-
phorus and sulphur with a common radicle.

In addition it is certain, if any weight is to be attached
to ultimate analyses, that the properties of these substances
do not depend entirely on their chemical composition. Ac-
cording to the analyses of Mulder, even, it is seen that two
sul)stances as dissimilar as it is possible for substances of
this class to be, namely, albumin of the white of Qgg and
fibrin, have the same ultimate composition. The ultimate
composition, then, does not seem to be important as
regards the general properties of the compound.

Notwithstanding all the labor that has been bestowed
upon the ultimate analysis of the substances under consid-
eration, the question of their composition does not seem
to be one of any great importance. The difficulties of such
analyses and the contradictory results in the hands of
skilful chemists show that a knowledge of the ultimate
composition of organic nitrogenous substances is of little
value as a means of distinguishing them from each other;
and such analyses throw no light whatever on their func-
tion in the economy. A careful review of the facts which
have been accumulated on this subject leads to the conclu-
sion that these bodies are of indefinite chemical composi-
tion. In the first place they are not crystallizable; second,
they may be made to assume different forms and proper-
ties by the action of imponderable agents, as in coagula-
tion by heat or galvanism, without losing or gaining any
elements; third, they are in a continual state of change, in
nutrition during life, without losing their properties, and
will continue to absorb oxygen and exhale carbonic acid
for some time after removal from the body,+ and shortly

* Robin and Verdeil, o/>. cii., tome iii., p. 282.

■f G. Liebig has shown that the muscles of the frog will continue to absorb
oxygen and exhale carbonic acid after they have been separated from the body,

ORGANIC NITROGENOUS PRINCIPLES 287

after these properties have disappeared, undergo the
changes of putrefaction; finally, there is no great differ-
ence between them in chemical composition, and almost
all the analyses made by chemists of equal skill present
great variations. Is there not, then, every support for the
assertion that their chemical composition is indefinite!
Either this assertion is correct or the methods of analysis
employed are inaccurate. As so much depends upon this
point, I venture to give a rapid sketch of the method of
analysis most commonly employed by chemists.

It is first ascertained, by a very simple process, that a
given substance, as albumin, is composed of certain ele-
ments, as carbon, hydrogen, oxygen, nitrogen, sulphur and
phosphorus. This being determined, it is deprived of
moisture; the fat is removed by ether and alcohol; and the
earthy salts, as far as possible, by dilute hydrochloric acid.
A carefully weighed quantity is then decomposed, and the
proportions of these elements are determined in the follow-
ing way :

A tube of the hardest glass, half an inch in diameter,
sixteen to eighteen inches long, and closed in a flame at
one end, is used for the decomposition, which is effected
by combustion. The oxidation is effected by means of the
black oxide. of copper, which is prepared for the purpose
perfectly pure, carefully powdered and completely freed
from moisture. The tube is first filled for two or three
inches with pure oxide of copper. The organic matter is
now to be carefully powdered, incorporated with oxide of
copper (it is best to employ five to eight grains of organic
matter for the analysis), taking care that none is lost, and
the mixture is introduced into the tube. The tube is now
to be filled to within an inch of its extremity with pure
oxide of copper.

In this part of the manipulation, care should be taken
to remove all moisture, as this would affect the quantity
of hydrogen obtained from the combustion. This may be
done by attaching the tube, after it has been filled, to one
opening of a small airpump, such as is used for this pur-
pose, the other being fitted to a bent tube filled with pumice
stone and sulphuric acid. By placing the combustion tube

so long as they retain their contractility. Lehmann, "Physiological Chem-
istry," Philadelphia edition, vol. ii., p. 474.

288 ORGANIC NITROGENOUS PRINCIPLES

in a long dish filled with warm water and exhausting the
air a few times, all the moisture may be removed.

As the tube is to be subjected to intense heat, it should
be wound with a narrow ribbon of sheet brass, which
will prevent its bending when it becomes softened. There
is now to be attached to the open end, by a smaller tube
fitted perfectly with a cork, a light tulnilar apparatus filled
with small fragments of chloride of calcium, the tube and
its contents having been previously weighed, and connect-
ed with this is a series of bulbs, called Liebig's potash bulbs,
partly filled with a solution of caustic potash, which is like-
wise to be carefully weighed. The heat may now be applied
to the combustion tube, which may be done in a long glass
furnace made for the purpose, or by surrounding it, well
supported in a long iron trough, with hot coals. The heat is
applied gradually, beginning at the nearer end of the com-
bustion tube. The organic substance is thus completely de-
composed; and if it is composed of carbon, hydrogen and
oxygen, like sugar, the analysis will be complete, this
combustion giving the carbon and hydrogen, the oxygen
being obtained by difTerence. As it is, all the hydrogen is
converted into watery vapor, which is absorbed by the
chloride of calcium, and the carbon, converted into car-
bonic acid, is absorbed by the potash. The weight of these
products is ascertained by taking the increase of weight of
the calcium tube and the potash bulbs, and the quantities,
of carbon and hydrogen are deduced therefrom.

There remain now the nitrogen and sulphur. The
same tube, with a little modification, may be used for car-
bon, hydrogen and nitrogen; but it is better to estimate the
nitrogen in another apparatus. For this purpose a com-
bustion tube is used similar to the one just described, pla-
cing at the closed end a few grains of bicarbonate of soda;
then the oxide of copper as before; next the mixture of
oxide of copper and the organic matter; next another layer
of pure oxide of copper, and last of all a layer of pure cop-
per reduced by hydrogen. The extremity is then con-
nected with one opening of the airpump, and to the other
is adapted a tube which opens under a receiver containing
mercury with a solution of potash floating on the top. The
air is then exhausted as completely as possible and the com-
bustion tube is connected with the receiver by opening both

ORGANIC NITROGENOUS PRINCIPLES 289

stopcocks of the airpump. It is necessary now to drive
out all the air from the apparatus, to collect the pure nitro-
gen in a gaseous form. For this purpose heat is applied to
the farther extremity of the tube, which decomposes the
bicarbonate and carbonic acid gas is evolved. It can be
seen that all the air is driven off, by the complete absorption
of the gas evolved by the potash in the receiver, showing
that pure carbonic acid is coming over. Another receiver
filled with mercury and a solution of potash is then substi-
tuted, the heat from the bicarbonate is withdrawn and
applied gradually from the anterior portion of the tube as
before. Combustion of the organic matter takes place,
which results in watery vapor, carbonic acid, which is ab-
sorbed by the potash in the receiver, and nitrogen, which
passes over and is collected in a gaseous form. Some of
the nitrogen is oxidized by this combustion, but as it passes
over the hot metallic copper in the nearer extremity of the
tube, the oxygen is retained and the nitrogen passes over
pure. After the combustion of the organic matter is com-
plete, heat is again applied to the bicarl:)onate of soda so
as to drive ofif what nitrogen remains in the tube, by the
evolution of carbonic acid. It remains now to remove the
receiver, substitute water for the mercury, measure the vol-
ume of the gas, taking the temperature carefully and bring-
ing the level of the water in the tube to that of the sur-
rounding liquid, and thence deduce its weight, which gives
the proportion of nitrogen.

The sulphur and phosphorus, if there is any, exist in
very small quantity. They may be estimated in the albu-
minoids without any great difficulty, by causing them to
unite with soda, as sulphuric or phosphoric acid, and then
precipitating with the chloride of barium for the sulphur,
and by a process a little more complicated, but not less
exact, for the phosphorus, which it is not necessary to de-
scribe here.

In this manner are obtained the weights, in a given
portion of albumin, of all its ingredients but the oxygen;
viz., carbon, hydrogen, nitrogen and sulphur. Subtract-
ing the sum of the weights of these substances from the
whole weight, gives the oxygen; and reducing to 100 parts
gives the ultimate composition.

I have given the process rather fully, to show how, with

290 ORGANIC NITROGENOUS PRINCIPLES

certain precautions, in the hands of one skilled in chemical
manii)n]ati()ns, it may be made as accurate as any operation
in inorj^anic chemistry. With a balance that will turn with
less than y^Vs of a gramme, and with care to avoid mois-
ture, etc., in the apparatus, the result should be always the
same, if the substance analyzed had always the same com-
position.

The next step is to establish the formula in equivalents.
If the substance used is an acid or a base which combines
wath any substance of known combining equivalent, this
could be easily done, by getting the weight of a combining
atom by experiment, calculating the proportions of its in-
gredients to this weight, and dividing the quantity of each
element thus obtained by its combining equivalent. But
in the case of the albuminoids, which are neutral, this can
not be done. A formula is calculated for them which ex-
presses the elements in the simplest manner so as to give
no fractions, generally giving an even number for the
atoms of carbon. Thus Liebig gives as the formula for
fibrin, Co98H228N4o092Si2.*

This review of the mode of ultimate analysis of organic
nitrogenous bodies makes it evident to one conversant
with chemical manipulations, that the contradictory results
obtained by different chemists are not due to imperfections
in the analytical process; indeed, the process is acknowl-
edged by chemists generally to be as accurate as that for
the determination of the composition of inorganic sub-
stances. The only way, then, to explain the contradictory
results obtained by dififerent chemists of equal skill and
reputation, is to assume that the chemical composition of
the principles is indefinite. While enough has been said,
perhaps, to convince the reader of this, it follows that im-
portant results are to be expected rather from a study of the
condition and behavior of these substances in the economy
than their decomposition into elements. When they have
been extracted from the bodv. they are bv no means in the
condition under which they normally exist. This being

* It is hoped that the reader of this article will remember that it was writ-
ten in 1863, when physiological chemistry was in its infancy. I have preferred
to publish the part relating to organic chemistry as it first appeared, correcting
only a few of the formulas, rather than attempt to adapt it to modern ideas or
omit it entirely.

ORGANIC NITROGENOUS PRINCIPLES 291

the case, it is for the physiological chemist to give their
quantity, properties, etc., so far as he can, in the condition
in which they really exist in life; the physiologist then takes
them and studies the phenomena in which they are con-
cerned. Here comes the important question: What is the
condition of existence of the organic nitrogenous elements
in the body? On the answer to this question depends the
mode of proximate analysis of the organized fluids of the
body, especially the blood, which is all important to the
physiologist.

Condition of Existence of Organic Nitrogenous
Substances in the Body. — In the ordinary proximate
analysis of the blood, by wdiich is meant an analysis giving
the proportions of proximate principles without any refer-
ence to their ultimate composition, the albumin and fil^rin
are put down in very small proportions. Fibrin is recog-
nized by its spontaneous coagulability, and albumin, by its
coagulability by heat and nitric acid; and it is evident that
fibrin may be extracted from the blood coagulated on
rods, and the albumin of the serum solidified by heat or
nitric acid, in quantities which are much greater than those
given in analyses. The physician finds it difificult to recon-
cile to his ideas of albumin and fibrin of the blood, the pro-
portions of sixty to sixty-five parts per thousand for albu-
min, and two and a half for fibrin. The reason why the esti-
mates fall so far below^ our ideas is that chemists never
have estimated the fibrin and albumin as they are separated
from the fluids by coagulation, which changes only their
form and not their weight, but after separating them in
this way, have subjected them to perfect desiccation. They
have given, therefore, not the weight of the principles as
they exist, not the fibrin and albumin in a condition to
nourish the body, but the desiccated substance, altered,
and its properties destroyed by this process. Physiologists
assume that fibrin and albumin are in solution in the water
of the blood, and that their natural condition, in a state of
purity, is that of a dry powder. In this case it is extremely
difficult to reduce these substances to their natural condi-
tion. When coagulated, which, according to this view, is
a precipitation, a large quantity of water persistently re-
mains, which it is very difficult to get rid of; and when got
rid of, the dry substance must be weighed quickly and with

292 ORGANIC NITROGENOUS PRINCIPLES

many precautions to avoid absorption of moisture. Other
matters are also found combined with coagulated organic
matters. All the salts found in the blood are united with
them as well as water; and in the proximate analyses, these
salts are generally not sei)arated from the organic substance
before it is weighed. This view, which is almost universally
held by physiologists, is the one which has guided all the
analyses of the organized fluids. Of the original works to
which I have access, that of Robin and Yerdeil, on " Ana-
tomical Chemistry," * is the only one in which I find any
dissent from the prevailing doctrine. They regard the or-
ganic elements of the fluids as naturally liquid and not in
solution; those of the semisolids as naturally semisolid;
and of the solids as solid. The contrary view seems to me
radically and entirely wrong; and all analyses of the organ-
ized fluids, made under the idea that organic substances are
in solution, fail to give anything like a correct notion of the
properties of these substances. The analyses of the blood
which are embodied in the latter part of this paper are the
only ones, so far as I know, which have been attempted
wnth reference to the real condition, as it seems to me, of
the organic constituents. They have been made on the
following principle:

The water which is contained in coagulated organic
substances and which may be driven ofT by dry heat is not
part of the water which held the organic matter in solution,
but an actual constituent of the substance, as much as car-
bon, hydrogen or nitrogen, and is indispensable to the
properties by which it is recognized as an organic principle.

It has already been shown that ultimate analysis does
not give an idea of the distinctive characters of different
organic matters. This depends upon certain characters
which are found in all principles of this class, and further,
upon certain properties which serve to distinguish them
one from another; and when deprived of their w^ater of
composition by desiccation, neither in their general prop-
erties nor in chemical composition are there any means of
recognizing them, unless it is bv their indefinite chemical
composition and the impossibility of making them assume
a definite or crystalline form.

* Op. cit., tome iii., p. I2i.

ORGANIC NITROGENOUS PRINCIPLES 293

First, in regard to their general properties! They all
undergo a change peculiar to themselves, called putrefac-
tion. This property, which is the one perhaps most dis-
tinctive of organic matters, disappears when they are de-
prived, even partially, of water; a fact that is well known
and of which there is a familiar example in the preservation
of meats. Again, when an organic substance is in a state
of putrefaction, it is capable of inducing the same change
in other elements of this class, by what is called catalysis,
or acting as a ferment. As water is necessary to putrefac-
tion, it consequently is necessary to the development of
this property. Principles of this class also undergo a
change peculiar to themselves in cooking, which is char-
acterized by the development of volatile empyreumatic
substances. Water is necessary to this change, for if ex-
posed to heat after water has been driven off, as has already
been seen in the study of the method of ultimate analysis,
they are resolved into their elements without undergoing
any such change. They also are capable of regaining their
water of composition after desiccation, possessing to an
eminent degree what is called the property of hygrome-
tricity, by which they are returned to the condition they
assumed when first coagulated. This coagulability is also a
peculiar property, entirely different from precipitation from
a solution. They can not be redissolved in the liquid from
which they are separated by coagulation. For example,
all of them, including albumin, are insoluble in alcohol;
but if albumin is coagulated by alcohol and afterward freed
from it, it can not be redissolved by pure water or by the
liquid from which it was separated. When once coagulated
they have undergone a change and can not be redissolved
except by means which change them still more. When
they have been coagulated and dried, reduced to what is
called a condition of purity, they can not be redissolved and
detected by their property of coagulation; for they are
changed and consequently are not in their natural condi-
tion.

Fibrin may be described as an organic constituent of
the blood, which possesses the propertv of coagulating
when removed from the body, giving this property to the
whole mass of blood, which separates after a time into
clot and serum. Albumin may be described as a principle

294 ORGANIC NITROGENOUS PRINCIPLES

of the same class, existing in the serum, which is coagulated
])}■ heat or nitric acid. These are naturally lluid, but coagu-
late, in the one instance spontaneously, and in the other,
by the means just mentioned. It can not be said that they
are principles composed of so many atoms of carbon, nitro-
gen, etc., because their comi)osition is indefinite. As re-
gards the proportion of these principles contained in the
blood, one can say only that after they have been separated
from this fluid and after all their water has been driven off,
there have been found 2^ parts of fibrin, and 60 or 70 of
albumin per i.ooo. This conveys little idea of the real
quantity, but only the quantity of anhydrous matter con-
tained in these substances, not the quantity of coagulating
fibrin and albumin found in the blood. Analyses giving
the quantities of these substances as nearly as possible in
their natural condition have never been made; although
they would seem the only ones that could convey any
definite idea of what is most important to know. I have
attempted to supply this deficiency, to a certain extent, in
Part II., on the Analysis of the Blood.

I have enumerated nearly all the properties by which
one can recognize organic nitrogenous substances, sepa-
rated from the living organism, as a class; namely, putre-
faction, the property of becoming ferments, changes in
coction, desiccation, hygrometricity and coagulation; and
all of these depend on the presence of water. Should it not,
then, be almost conclusive from these facts that water is
a necessary and very important element in their constitu-
tion! It is true that it is separated with great facility, and
that its union wath the other constituents is not very pow-
erful; but this is no argument against the fact of its being
in a condition of actual union. There are many substances
in the inorganic world which have a union no more power-
ful than that of water in organic matters. Take the single
example of the bicarbonate of soda. The second equiva-
lent of carbonic acid is driven off by gentle heat and even
by exposure to the air at the ordinary temperature, leaving
the salt in the condition of a carbonate.

There is another circumstance in connection with the
mode of union of water with other ingredients to form an
organic body which serves to distinguish it from mere
solution. When a solid substance, as a salt, is in solution

ORGANIC NITROGENOUS PRINCIPLES 295

in any liquid, it requires a certain quantity of the liquid to
dissolve a certain quantity of the solid; but beyond this the
liquid may be increased indefinitely, the solid having the
same relation of solution to the whole mass. On the con-
trary, when one chemical compound, as nitric acid, unites
with another, as with soda, one equivalent of the one
combines with one equivalent of the other, and if more
of either one is added, it does not enter into combination.
I regard the organic substances found in the liquids of
the body as naturally liquid and mixed with the other
liquids; the water which enters into their composition, as
represented by the water which they contain when sepa-
rated from the other liquids by coagulation; and this quan-
tity of water, though not absolutely definite, is as definite
in its proportion as are the other ingredients. It is re-
stricted within definite limits; and although, w'hen liquid,
like many other liquids it may be mixed with an indefinite
quantity of water, when separated by coagulation, water
will always be found in about the same proportion.

There is another point of view, by far the most impor-
tant physiologically, from which to study this question of
the natural condition of the organic constituents of the
liquids. Do they conduct themselves in the processes of
nutrition like the inorganic substances, which are undoubt-
edly held in solution, or like substances naturally liquid?

This question seems to me very easily answered. The
processes of nutrition of the organic constituents of the
body consist in a change of the liquid organic substances,
principally the albumin and fibrin, into those which are
semisolid and solid, like myosin, ossein, etc. In the proc-
ess of these changes, water is of course absolutely neces-
sary, and is deposited with the other constituents of the
organic matters. It, as well as the carbon, hydrogen and
nitrogen, is necessary to the constitution of the myosin
and ossein and is involved in all the changes incident to
nutrition.

Having special reference to the blood and the organic
substances which it contains, the relations between this
fluid and the tissues constitute one of the most important
and interesting of physiological inquiries. In the organic
constituents of the solids and semisolids of the body reside,
undoubtedly, the vital properties which lead them to regen-

296 ORGANIC NITROGENOUS PRINCIPLES

erate themselves at the expense of the circulating fluid;
and in the tissues and organs, as well as in the blood, the
organic matters are always united with inorganic salts, as
well as with water. Of these salts, some, in connection
with organic matter, go in great measure to make up the
tissues, as the phosphate of lime in the bones; wiiile others
seem by their ])rcsence to regulate the nutritive processes,
like the chloride of sodium, wdiich is more abundant in
the blood than in the tissues. Organic nitrogenous mat-
ters, whether fluid, semisolid or solid, never exist alone,
but always in combination with inorganic substances.
It is impossible, indeed, in extracting the organic sub-
stances from the body, to free them entirely from inorganic
salts; and the fibrin and albumin of the blood I have found
to contain all of the salts which exist in that fluid. The
blood contains all of the elements, both organic and inor-
ganic, which are necessary for the regeneration of the tis-
sues. The inorganic elements are deposited unchanged,
and in the organic elements alone resides that property
of mutual convertibility which forms myosin, chondrin,
ossein, etc., out of albumin and fibrin. In this process
of change there is a deposition of the salts, which can
not take place by itself but must be involved in the deposi-
tion of organic matter. This process is not to be explained
by the laws of chemical attraction or represented by a
change in chemical formulas. It takes place only in organic
living bodies; and the more we attempt to elucidate it by
investigations of a purely chemical nature, the farther we
remove ourselves from a comprehension of the essence of
nutrition. We must learn to look on processes like this
as physiological and not chemical; and as we never have
constructed, and perhaps never shall construct, a single or-
ganic nutritive substance out of its elements, or changed
one into another, so we shall ever fail to comprehend the
phenomena of change and the mystery of their construction
in the body, if we persist in endeavoring to adapt these
phenomena to the laws which regulate the composition and
changes of inorganic substances. When w^e study the com-
position of these substances, we should take them as we
find them, and not try to reduce them to a condition ap-
proximating that of minerals. The absence of useful results
following the labors in this direction of so manv chemists

ORGANIC NITROGENOUS PRINCIPLES 297

should be a warning to us to leave the beaten track. When
we study their properties, we have already seen that it is
necessary to take them as they are, combined with water,
•or these properties are lost. When we come finally to study
their functions in the economy, we find that they not
only contain water, but inorganic substances, which are in-
dispensable to the great function of nutrition, and which
can not be separated from the organic. We must in this
study recognize the following important facts:

First. Organic nitrogenous substances are the only ele-
ments of the body in which reside the properties of destruc-
tion and regeneration during life. Fats, sugars, and inor-
ganic salts operate with them, and by virtue of this prop-
erty.

Second. They are of indefinite chemical composition;
and no great physiological importance is to be attached
to ultimate analyses. They are unstable, in a state of con-
tinual change during life and soon alter after death or after
removal from the body.

Third. They assume the consistence of the tissue or
fluid in which they exist. They are solid in the solids, like
bone; semisoHd in the semisolids, like muscle; liquid in the
liquids, like the blood. They are not dissolved in water,
but water is an ingredient, and its quantity determines
their consistence.

Fourth. In the body they never exist alone, but are
always combined with inorganic substances, which accom-
pany them in the changes which they undergo in the proc-
esses of nutrition and disassimilation.

Fifth. As all the proximate analyses of the organized
fluids, particularly the blood, have been made with the idea
that the organic ingredients were solids in solution in
water, these quantitative analyses give, not the propor-
tions of fibrin or albumin, but dried fibrin and albumin,
the original substance subjected to a process which drives
ofif its most important constituent and which alters its
properties. Such analyses, as representing real quantities,
.are erroneous.

298 ORGANIC NITROGENOUS PRINCIPLES

PART II

Analyses of the Blood with Reference to its
Organic Constituents. — From the review just given of
the organic constituents of the body and the intimate rela-
tion seen to exist between the tissues and the blood, it
is evident that an analysis of the nutritive fluid, espe-
cially with reference to its organic constituents, is of great
interest and importance. This has long been recognized;
and in late years a great part of the labors of investigators
in physiological chemistry have been devoted to this sub-
ject. It is not my purpose here to consider any but the
organic principles of the blood. The constitution of this
fluid, in its entire physiological and pathological relations,
is too extended ^ theme to be considered in this place.
The fact that the blood contains certain excrementitious
substances shows that this fluid is connected with the waste
as well as the repair of the system. The pathological im-
portance of this has been settled experimentally by the dis-
covery of the accumulation of excrementitious matters in
the circulating fluid, giving rise to certain pathological con-
ditions; as for example, urea, producing a condition of
the system known under the name of uremia; and more
lately, the discovery of the character of cholesterin as an
excretion and its accumulation in the blood, under cer-
tain conditions of the liver, constituting cholesteremia.*
These are only two examples where diseased conditions of
the system have been clearlv shown to depend upon the
accumulation of a specific excrementitious substance in the
blood; but the work in this direction is but begun; and
I venture to predict that more light will be thrown on
pathology by the discovery of new toxins in the blood,
dependent on defective excretion, than by any other line
of experimental inquiry.

The proximate analyses of the blood up to this time
have been made under the supposition that the organic
matters, fibrin and albumin, are solid matters in solution;
but according to the \'iews advanced in Part I.; namely,
that their real condition is one of fluidity, and that when

* See an article on a " New Excretory Function of the Liver," by the
author, published in the number of this Journal for October, 1862.

ORGANIC NITROGENOUS PRINCIPLES 299

deprived of water they lose one of their most. important
constituents, this mode of analysis is inadmissible. The
actual quantities of fibrin and albumin can no more be rep-
resented by the residue of evaporation than by the residue
of calcination, which latter would leave only inorganic mat-
ter. Before giving, however, the processes by which I
have attempted to estimate the c^uantities of undried fibrin,
albumin and globules in the circulating fluid, I shall give
a rapid review of the methods of proximate analysis which
are now generally employed.

Berzelius, followed soon after by Marcet, made the
first extended quantitative analyses of the blood. He ana-
lyzed the serum of human blood and indicated certain quan-
tities of albumin, lactate of soda, muriate of soda, etc. He
put the quantity of dried albumin at 80 parts per 1,000,
which is about the proportion given in the analyses of chem-
ists of the present day. His researches w^ere published in
1808 and were followed by the analyses of Marcet, in 181 1,
which gave nearly the same results. In 1823 Prevost and
Dumas published their researches on the composition of
the blood, with a full account of their process. This proc-
ess, with slight modifications, is the one employed gener-
ally at the present time. The following are the principal
steps in the analysis: The filjrin is separated from a weighed
quantity of blood by whipping with a bundle of broom-
corn, carefully collected, dried and weighed. Another
specimen of blood is set aside to coagulate, and after it has
fully separated into clot and serum, the clot is dried and
weighed; the proportion of fibrin ascertained from the first
specimen is subtracted, which gives the quantity of dried
globules. The serum is then evaporated to dryness, the
residue extracted thoroughly with boiling water, e^her and
hot alcohol, to remove inorganic salts and fats and af^^er-
ward weighed, which gives the proportion of albumin. The
fats are easily extracted with ether; and the inorganic con-
stituents are estimated after incineration, by a process
which it is not necessar}^ to descril:!e. This process has
been followed, with unimportant modifications, by a num-
ber of chemists, who have done little more, in regard to the
albumin and fibrin, than confirm the observations of Pre-
vost and Dumas. Among these may be mentioned Andral
and Gavarret, Becquerel and Rodier, Sheerer, and Simon.

300 ORGANIC NITROGENOUS PRINCIPLES

Among these observers, ])crhaps, the process adopted by
Becqiierel and Rodier is one as generally accepted by
physiologists as any, and I shall therefore translate from
their work, entitled " Traite de chimie pathologique," so
much of it as refers to the estimation of the fibrin, albumin
and globules:

" First Series of Operations. — This is designed to furnish :
First, the density of the blood and that of the serum; second, the
weight of fibrin and globules and of the solid matter of the serum
taken as a whole. These processes are founded on the same prin-
ciple which served as the basis of the process devised long since
by M. Dumas. We suppose that all the water contained in the
blood forms part of the serum and should be attributed to it. Still,
in admitting this principle, we have not always applied it in the
same manner.

" The following is our mode of operation :

" We practise upon the person whose blood we wish to analyze,
a bleeding of about 375 grammes. The blood which first flows
from the vein is received in a glass vessel, graduated and capable
of holding about 125 cubic centimetres of this liquid. We collect it
and whip it with a bundle of broomcorn. We thus obtain the
fibrin, which we must wash, desiccate and weigh.

" The blood, thus defibrinated, is then put aside to serve for
other operations.

" The blood which flows from the vein, after these 125 cubic
centimetres, is collected with care in a vessel of the capacity of 250
to 300 cubic centimetres and left to itself. This blood coagulates,
and once the coagulation effected, we separate carefully the serum,
which we put aside in a vessel ; as to the clot, after having taken
note of its physical characters, we may set it aside.

" Let us see now what we do ; first, with the defibrinated blood ;
second, with the serum.

" A. The defibrinated blood is first weighed at a definite tem-
perature in a glass specific-gravity bottle.* We compare then the
weight which we obtain in this operation with the weight of the
same volume of distilled water ; and we thus have, by a very sim-
ple calculation which it is useless to reproduce here, the exact
weight of the 125 cubic centimetres of blood which we whipped to
separate the fibrin, ana consequently the weight of this same fibrin
contained in i.ooo grammes of blood. Once this operation effected,
we take a definite quantity of defibrinated blood, which we weigh,
which we desiccate, which we afterward weigh anew, and we thus
have the weight of the quantity of water which it contains. Let
us take, for example, in order to make ourselves better vmderstood,
arbitrary numbers which we shall make use of also to deduce the
weight of the globules: 100 grammes of defibrinated blood, liquid,

* All our specific-gravities were taken at a temperature of 12° (53.6° Fahr.)
and compared exactly with distilled water at the same temperature.

ORGANIC NITROGENOUS PRINCIPLES 301

gives 20 parts of solid material and 80 parts of water. Then 20
parts, thus dried, are calcinated to give us the inorganic matters;
we shall return to this.

" B. The serum. — After having determined the specific gravity
of the serum, we take a given quantity of this liquid which we
weigh, which we desiccate, which we afterward weigh anew; the
difference of these two weights gives that of the water; as, for ex-
ample, 100 grammes of liquid serum having given 10 grammes of
solid matter and 90 grammes of water. These operations termi-
nated, we possess the figures necessary to deduce the weight of the
globules and that of the solid matters of the serum contained in 100
grammes of defibrinated blood. Indeed, as all the water of the
defibrinated blood should be attributed to the serum, we must make
the following proportion :

80 X 10 „

80 : .r : : go : 10 or .r = = 0.0 p;r.

90

" This proportion 8.8 represents the sum of the solid matters of
the serum contained in 100 grammes of defibrinated blood, and sub-
tracting that from 20, the weight of this blood desiccated, we have
1 1.2 which represents the weight of the globules, and in calculating
the whole to 1,000, v^'e have 1,000 grammes of blood, containing:

Water 800 grammes.

Globules 112

Solid matters of the serum 88 "

" The weight of the fibrin has been given by the first operation
and should be added. Its weight is so small in proportion to 1,000
grammes of blood, that we may neglect a little correction which we
should have to make for the weight of the fibrin in addition to the
1,000 grammes of defibrinated blood.

" Such is the first series of operations ; for the second we shall
make use of the dried serum, and for the third, of the defibrinated
blood calcinated.

" Second Series of Operations. — These operations are de-
signed to give the weight of the extractive matters and that of the
fatty matters. The following is our mode of operation :

" The serum, having been dried with precaution in an ' etuve,'
and pulverized with the greatest care, is treated repeatedly with
boiling water until this water has completely freed it from every-
thing which it can dissolve. These last are, on the one hand, ex-
tractive matters, such as osmazome, the coloring matter of serum,
etc., etc., and on the other hand, the salts which are in solution in
the serum and are in a free state.

" The serum, thus extracted with water, is dried again and
weighed, the difference from the weight obtained by the first weigh-
ing indicates that of the matters we have mentioned and which the
water has removed. The product of the second desiccation is then
treated with boiling alcohol at 90°, until it is completely extracted.
The insoluble residue is pure albumin, of which we may take the
weight after having dried it. As to the boiling alcohol, it holds
in solution all the fatty matters, which can be separated by em-

302 ORGANIC NITROGENOUS PRINCIPLES

ploying the process indicated by M. F. Boudet, and of which we
think it unnecessary to give a description. It gives the serolin,
cholesterin and saponifiable fats." *

The above qtiotation is a fair representation of the mode
of analysis most commonly made use of at the present day.
It differs, however, very little from that indicated by Du-
mas. There are certain objections to this process, aside
from those which have reference to the estimation of fibrin
and albumin, which have long engaged more or less the
attention of physiological chemists and are acknowledged
to be well founded. It will be observed that all the water
is attributed to the plasma, while the globules are estimated
dry. This is manifestly faulty, as the most cursory micro-
scopic examination of the blood-globules is suf^cient to
show that they have a consistence dependent upon the
presence of a certain quantity of water; and though it may
be convenient to estimate these bodies dry, such an esti-
mate gives no idea of their real proportion. This was ap-
preciated as long ago as 1828, by Denis, who attempted to
give the proportions of moist globules by a process which
had avowedly little accuracy and which he afterward aban-
doned for the original process of Dumas. f In 1844
Figuier published an analysis of the blood which gives
an estimate of the moist globtiles by a process that I have
employed in the analyses which follow, and which seems
to me to give sufficiently accurate results, although Denis
does not consider it superior to his own. This process was
accepted by Dumas with some modifications which are de-
scribed by him in the " Annales de chimie et de physique "
for 1846, p. 452. The process of Figuier depends on the
property which certain saline substances have, mixed with
the blood, of retaining the globules on a filter. The modi-
fication by Dumas is intended to avoid a difficulty which
sometimes occurs from alteration and liquefaction of the
globules, by which some pass through a filter and are lost.
It consists in passing a continuous current of air through
the filtering fiuid, which prevents this change. In the anal-
yses I have made I have not found it necessary to adopt
this precaution.

lerel and Rodier, op. cit., p. 21.
[emoire sur le sang." Par P. S. Denis (de Commercy). Paris, 1859,
P- 51.

* Becque
t " Mem

ORGANIC NITROGENOUS PRINCIPLES 303

The following is the process described by Figuier,
translated from the '* Annales de chimie et de physique." *
It was not used by him to determine the proportion of
moist globules; the globules are merely separated from the
blood, dried and estimated in this condition Hke the other
organic matters.

" The blood furnished by a venesection is whipped on its dis-
charge from the vein according to the process of IM. Dumas. The
fibrin separates and adheres to the little broomcorns. The liquid
is passed through a fine cloth to separate that portion of the fibrin
which does not adhere to the broom. This fibrin is then washed
in a current of water, then dried in a water-bath, and weighed,
after having been treated, if desired, with ether to remove a little
fatty matter.

" In taking the total weight of the blood which has given this
quantity of fibrin, we shall have the proportion of the fibrin to the
other elements of blood.

" We then take 80 or 90 grammes only of the defibrinated blood
which we treat with about twice its volume of a solution of sulphate
of soda marking sixteen to eighteen degrees in the aerometer of
Baume, and this is thrown on a half-filter weighed in advance, and
previously moistened with the saline solution ; with these precau-
tions the serum filters quite rapidly with a yellowish color.

" We understand that, to remove from the globules that remain
on the filter, the solution of sulphate of soda with which they are
impregnated, we can not simply wash the filter, for that would dis-
solve a portion of the globules and the fluid would pass red like
the blood. But a property peculiar to the globules allows us, hap-
pily, to surmount this difficulty. When they are heated to 90° Cent.,
as Berzelius has already seen, the globules are coagulated entire,
and the entire mass becomes concrete without yielding to the water
any of the organic matter. We have only, then, to place the filter
in a capsule containing boiling water, repeating this process two or
three times. The sulphate of soda is dissolved and the water takes
almost nothing from the globules, for the fluid is almost colorless
and does not contain any organic matter appreciable by tannin or
corrosive sublimate.

" To separate the albumin from the filtered serum it suffices to
carry it to the point of ebullition in a capsule. The albumin coagu-
lates ; it is collected in a little net of fine cloth ; it is washed and
weighed, after having been dried, by the water bath. Finally, to
determine the quantity of water contained in the blood, we take
twenty or twenty-five grammes which we evaporate to dryness in
a water bath. The weight of the residue indicates the proportions
of water and solid elements.

* " Sur une methode nouvelle pour I'analyse de sang, et sur le constitution
chimique des globules sanguins." Par M. L. Figuier. — "Ann. de chim. et
de phys.," 1844, 3""® serie, tome xi., p. 506.

304 ORGANIC NITROGENOUS PRINCIPLES

" The soluble salts of the serum are represented by the differ-
ence of the weight of the blood employed and the sum of the albu-
min, water, fibrin and globules determined directly."

The above is a very simple and accurate process for de-
termining the globules and organic constituents of the
blood, but according to the view already indicated, it is
open to the same objection as the other, as it gives the
quantity of these ingredients dried, and not as they really
exist.

Schmidt, of Dorpat, recognizing the necessity of a
proper estimate of the moist globules, endeavored to estab-
lish a certain proportion of water to be constantly attributed
to them; so that by adding this quantity to the estimate of
the dry globules by Prevost and Dumas and others, their
results could be made use of. He endeavored to do this
by comparative microscopic measurements of the moist
and dry globules, and he arrived at the conclusion that the
dry globules multiplied by four would give the cjuantity of
moist globules. Though this process was adopted by Leh-
mann as the most accurate, it is evident that it can not pos-
sibly be exact; especially if the proportion of water in the
globules is not always the same, as is stated by Zimmer-
mann.

Zimmermann attempted to give the proportion of water
in the globules by estimating the quantity of chlorides in
the blood, assuming, with Berzelius, that all the chlorides
are contained in the serum and there exist none in the
corpuscles. He estimated first the proportion of the chlo-
rides in the serum, then the quantity of chlorides in a
given quantity of blood, whence he deduced the propor-
tion of serum in the blood; then subtracting the water
contained in the serum from the water contained in the
entire blood, he obtained the proportion of water in the
globules. As it is by no means certain that the blood-
globules contain none of the chlorides, this process can
not be accepted.

Other methods of a very complicated character have
been proposed by Vierordt, Le Canu and Lehmann, which
it is not necessary to describe, as they present no advan-
tages over the foregoing.

The most recent process that has been proposed
originated with Denis and was published by him in

ORGANIC NITROGENOUS PRINCIPLES 305

1859.* His manipulations to get rid of the interstitial
serum of the globules are complicated, difficult and of
questionable efficacy. He arrives, by this process, at
very nearly the results I have obtained by the process
of Figuier, which, from its simplicity, is much to be
preferred.

From this brief review of the processes for the analysis
of the blood, especially with reference to the fibrin, albu-
min and globules, it is seen that no analysis has ever been
made, or even attempted, which would give the real quan-
tities of fibrin and albumin; in all of them the dry residue,
and not the substance itself, is given. In the estimation
of the globules, however, this desiccating process is so
evidently faulty that efforts have been made to estimate
them in their moist state, or as they really exist. As yet
there is no one process for arriving at this end that is
generally accepted by physiological chemists. From my
own observations in regard to all the constituents under
consideration, it seems impossible to make an analysis
which will be perfectly accurate; but absolute accuracy is
not indispensable. One can get near enough to the truth
for all practical purposes; and as the comparison of differ-
ent analyses made in the same w-ay gives them much of
their value, it is best to fix upon that process for estimation
of the moist globules which is simplest and w-hich seems
to give the most reliable results. It is manifestly better to
get an approximate idea of the fibrin, albumin and globules
of the blood in the condition in which they really exist than
to take the quantity of dry residue, which gives no idea
whatsoever.

Having in view, then, the condition of existence and
functions of the organic constituents of the blood, it is only
an estimate of these principles in a moist state that can
give any clear idea of their proportions.

Analytical Process. — In the process which I shall
describe, I have endeavored to simplify manipulations so
far as is consistent with reasonable accuracy, deeming it
important to put such investigations within the reach of
every one rather than to complicate the process by precau-
tions which are designed to avoid errors so slight that they

* Denis, op. cit.

3o6 ORGANIC NITROGENOUS PRINCIPLES

may practically be disregarded. T3umas has shown that the
composition of the blood is not precisely the same at the
beginning and the end of a bleeding; and he recommends,
therefore, that the blood be drawn in ecpial quantities in
four vessels, defibrinating the specimens in the second and
third, and allowing those in the first and fourth to separate
into clot and serum. By comparing the results of the sepa-
rate analyses, a correction may be made. I have not found
it necessary to use more than two specimens of two to four
ounces each; and with this quantity such a precaution is
not necessary.

It is very important to cover the vessels which contain
the blood and to weigh them as soon as possible; for the
specimens lose weight very rapidly by evaporation, as has
been shown by Becquerel and Rodier,* which would seri-
ously interfere with the quantitative analysis.

The blood to be analyzed is taken from the arm and
received into two carefully weighed vessels. The quantity
in each vessel may be two to four ounces. One of the speci-
mens is whipped with a small bundle of broomcorn, pre-
viously moistened and weighed, so as to collect the fibrin;
and after the fibrin is completely coagulated, the whole is
carefully w^eighed, deducting the w^eights of the vessel and
broomcorn, w'hich gives the weight of the specimen of
blood used. The other specimen is set aside to coag-
ulate.

The first specimen is to l)e used for the estimation of
fibrin and globules; the second is set aside to coagulate
and is used to estimate the albumin.

The first specimen of blood is now^ passed through a
fine sieve to collect any fibrin that may not have become
attached to the wisp; the fibrin is stripped from the wasp
and washed under a stream of water. This may be done
very rapidly by causing the water to flow through a small

* In experiments by Becquerel and Rodier with reference to the loss of
weight by evaporation, the following results were obtained. The blood was
drawn into a porcelain vessel about two and a half inches in diameter :

Weight of blood on being Weight of blood 2 'Weight of blood 24

drawn from the vein. hours after. hours after.

1st Exp 13-242 grammes 13-070 grammes 11. 510 grammes

2d Exp. . . . 14.905 " 14-727 " I2.g77

3d Exp 22.453 " 22.308 " 20.337

— " Chimie pathologique," p. 31.

ORGANIC NITROGENOUS PRINCIPLES 307

strainer, so as to break it up into a number of little streams,
and kneading the fibrin in the fingers, doing this over a
sieve so as to catch any particles that may become detached.
In this way it may be freed from the globules in five or ten
minutes. The fibrin thus washed is then freed from adher-
ent moisture by bibulous paper and is weighed as soon as
possible. The following simple formula gives the propor-
tion per 1,000 parts of blood:

Weight of blood used : Weight of fibrin : : 1,000 : Fibrin per 1,000.

The next step is to estimate the globules. For this pur-
pose a portion of the defibrinated blood, which is carefully
weighed, is mixed with twice its volume of a saturated so-
lution of sulphate of soda and thrown on a filter which has
been carefully weighed, moistened with distilled water, and
just before receiving the mixture of blood and the sulphate
of soda is moistened with the saline solution. The fluid
which passes through should be about the color of the
serum; and if a few globules pass at first the fluid should
be poured back until it is clear. The funnel is then covered
and the fluid allowed to separate, the blood-globules being
retained on the filter. The filter and funnel are then
plunged several times in a vessel of boiling water, by which
all the sulphate of soda which remains is washed out and
the blood-globules are coagulated without changing their
weight. The funnel should be covered again and the water
allowed to drip from the filter, after which it is weighed,
deducting the weight of the moist filter previously ob-
tained, which gives the weight of the globules. The pro-
portion of globules to 1,000 parts of blood is obtained
by the following formula:

T^ Gu ■ ^ J ui J J /-I u 1 Defibrinated : Globules per

Uenbnnated blood used Globules : . 1 ■ . „„ , ^^^

blood per 1,000 1,000.

The next step is to estimate the quantity of albumin
in the serum and thence its proportion in the blood. For
this purpose I first ascertain the quantity of serum in
1,000 parts of blood, which is done by subtracting the
sum of the fibrin and globules per i.ooo from 1,000. Hav-
ing done this and waited ten or twelve hours for specimen
No. 2 to separate completely into clot and serum, I take
a small quantity of the serum, about half an ounce, care-
fully weigh it, and add suddenly twice its volume of

3o8 ORGANIC NITROGENOUS PRINCIPLES

absolute alcohol. The albumin is thus thrown down in
a grumous mass, and the whole is thrown on a filter pre-
viously moistened with alcohol and weighed. The funnel
is immediately covered, and the fluid separates from the
albumin very rapidly. I ascertain that no fluid albumin
passes through the filter by testing the fluid with nitric
acid. After the filter has ceased to drip, it is weighed, and
the weight of all)umin ascertained by deducting the weight
of the filter. The proportion of albumin to i,ooo parts of
blood is obtained by the following formula:

Serum used : Albumin : : Serum per i,ooo : Albumin per 1,000.

The above process is very simple and easy of applica-
tion; and if the directions are carefully followed, it will give
quite uniform results. I have repeatedly satisfied myself of
this fact by subjecting two specimens of the same blood to
the same process, which was followed by almost identical,,
and in some instances, identical results. For example, in
an examination of human blood, two equal quantities (34.20
grammes) of defibrinated blood were analyzed for globules;,
one specimen gave 16.40 grammes of globules, and the
other 16.43 grammes. This part of the process would
seem more open to the charge of inaccuracy than any; yet
the difference in the results of the two analyses is so slight
that it may be disregarded.

In washing the fibrin I was at first led to use a saline
solution instead of pure water; but as the mass evidently
gained weight treated in this way, I afterward employed
simple water. Of two specimens of fibrin from the same
blood, one, w'hich was washed with a solution of common
salt, spec. grav. loio, gave 10.28 parts per 1,000, and the
other, W'hich was washed with water, gave but 8.82 parts, a
diminution of about 14 per cent.

I tried most of the methods for coagulating the albumin
before fixing upon the one by absolute alcohol. The object
was to get it as nearly as possible in its natural condition,
simply changing its form from fluid to semisolid, without
adding anything which would decompose it or unite with
it; and absolute alcohol seemed better than heat, nitric
acid, the galvanic current or any of the agents by which it
is coagulated. It is necessary to add about twice the vol-
ume of alcohol, and to do this suddenly; when the fluid

ORGANIC NITROGENOUS PRINCIPLES 309

Avhich separates by filtration will be found to contain not
a trace of albumin. Repeated trials of different specimens
of the same serum, producing generally identical results,
led me to fix upon this as the best method.

It is easy to see, after a few trials, why this method of esti-
mation of these organic matters has not been employed by
chemists. The difficulty is to fix the standard of moisture;
for the specimens, even when on the balance, lose weight
bv evaporation every moment. This, of course, is opposed
to the ideas of accuracy which are necessarily ingrafted into
the character of every good analytical chemist. One who is
accustomed to weigh for hours, perhaps, to avoid a possible
error of the thousandth of a gramme, could hardly consent
to accept a weight which is changing every moment. Com-
plete desiccation is the only absolutely definite standard;
and in all these organic animal analyses, the substance is
weighed and exposed to heat over and over again, until it
ceases to lose weight. Although such accuracy is indis-
pensable in some processes in physiological chemistry,
here it is not only unnecessary but impossible. It is part
of the nature of these substances to change every moment;
and when they are reduced to such a condition that they
will no longer change, they have lost all their characteristics
as organic principles. What is most desirable is an approxi-
mate physiological idea of their real quantity; and this is
better than the most accurate estimate of their dry residue.

By the process just described, I have arrived at the fol-
lowing results in the few quantitative analyses of the blood
for organic principles I have made. The variations in these
constituents in different states of the human system and in
different animals are interesting and important; but this de-
mands time and a long series of investigations. In the
few observations here presented, it has been my object to
show the advantages of the analytical process employed, so
that it can be applied by others, and to give merely an
analysis of the healthy human blood; and the various ex-
periments have been made rather to be able to fix upon a
definite process than with a view to comparative results.
Attention has been directed only to fibrin, albumin and
globules, for reasons which have already been fully given.
The number of analyses of human blood is not large, for
it is not easy to obtain healthy specimens; and with the

3IO ORGANIC NITROGENOUS PRINCIPLES

improved notions of therapeutics, it is difficult, also, to ob-
tain specimens of blood from patients. The specimens of
human blood were taken from the arm. The blood of the
ox was taken in the slaui^hter house, the vessels of the neck
being divided after the animal had been knocked on the
head.

Examination I. — Human Blood, Male. — This speci-
men of blood is assumed to be perfectly normal. The sub-
ject is twenty-seven years of age, male, perfectly healthy
and has never suffered from disease. The weight is one
hundred and seventy pounds. The blood was taken from
the arm at i p. m. The last meal had been taken at 8 a. m.

The following is the result of analysis of the blood:

Fibrin 8 . 82 parts per i ,000.

Albumin 329. 82 "

Globules 495 . 59 " "

Examination II. — Human Blood, Male. — This
specimen was taken from a man, thirty-seven years of age,
calker by trade, weight two hundred pounds, but rather
corpulent than muscular. He had slight constitutional
syphilis, and had been taking the iodide of potassium, gr. x
three times a day, for about three weeks. He was bled
from the arm about two hours after dinner.

The following is the result of analysis of the blood:

Fibrin 7 . 44- parts per i ,000.

Albumin 277. 55 " "

Globules 480.44 " "

Examination HI. — Human Blood, Female. — This
specimen was taken from a female, twenty-seven years of
age, weight one hundred and sixty pounds, dark complex-
ion, and perfectly healthy, with the exception of a slight
plethoric tendency, as indicated by occasional epistaxis
which had troubled her for a few days. She menstruated
regularly, the last time about two weeks ago. She took
lunch about 11 a. m. and was bled at 2 p. m. The blood
coagulated rapidly, and in twelve hours the clot presented
the " buffed and cupped " appearance. A portion of the
defibrinated blood which was not used in the analysis pre-
sented a remarkable example of gravitation of the globules
and separation from the serum. It stood in a graduated
glass, and the upper half, by actual measurement, con-

ORGANIC NITROGENOUS PRINCIPLES 311

sisted of pure serum.* Two days after the venesection
the woman still enjoyed perfect health.

The following is the result of analysis of the blood:

Fibrin 16.81 parts per i ,000.

Albumin 3ii-i8

Globules 484 .51 " "

Examination IV. — Human Blood, Female. — This
specimen was taken from a woman, twenty-eight years of
age of somewhat anemic aspect. She had been taking an
ounce of sulphate of magnesia every second day for two
weeks. The medicine usually operated three or four times.
She was bled at 2 p. m., having eaten nothing since 8 a. m.

The following is the result of analysis of the blood:

Fibrin 1 1 ■ 34 parts per 1,000.

Albumin 219.47 " "

Globules 382.95 " "

Examination V. — Blood of the Ox. — This speci-
men was taken from a small ox, the throat being cut after
he had been knocked in the head.

The following is the result of the analysis:

Fibrin H- 52 parts per 1,000.

Albumin 195 , 24 "

Globules 623 . 36 " "

Examination VI. — Blood of the Ox, — The animal
from which this. specimen was taken was rather larger and
more vigorous than the one which furnished the blood for
Examination V.

The following is the result of the analysis:

Fibrin 16.27 parts per 1,000.

Albumin 200.85 "

Globules 568.61

Of the four observations on the human subject, but
one. Examination I., can be taken as a fair example of nor-
mal blood. This analysis shows that the moist globules
constitute about onv.-half of the entire mass of blood; an

* This tendency of the globules to gravitate in defibrinated blood was no-
ticed by Poiseuille, and is mentioned by Bernard who advances the view that
one of the important functions of fibrin is to keep the globules in uniform sus-
pension. (Bernard, " Liquides de I'organisme," tome i., p. 465.) This is by
no means invariable. I have seen specimens of blood in which there was no
gravitation of the globules Such a complete separation as was presented in
this specimen of blood is very remarkable.

312 ORGANIC NITROGENOUS PRINCIPLES

estimate which does not differ much from the restdts ob-
tained by others who have endeavored to solve this ques-
tion. Denis gives the proportion of globules in a person
" 30 years of age, strong constitution, sanguine tempera-
ment," 489.52 parts per 1,000.* Schmidt estimates the
moist globules at 513 per 1,000 for the male and 396 for
the female. f Lehmann estimates them at 496 i)er i,ooo.:{;

Albumin constitutes by far the greatest part of the other
organic matters and equals nearly one-third of the entire
weight of blood. As this is undoubtedly the element which
nourishes the organic parts of the tissues, which form the
greatest part of the body, its pre])onderance is not surpris-
ing. The fibrin, even by this mode of analysis, is seen to
exist in small quantity, sufficient, however, to firmly coagu-
late the whole mass of blood. One is surprised in washing
a large clot to see how little fibrin is necessary to thus en-
tangle all the globules. The salts were found to exist in
the fibrin, albumin and globules, which were all tested for
chlorides, carbonates, phosphates and sulphates.

Taking Becquerel and Rodier as authority for the pro-
portion of fatty, inorganic and extractive matters, the fol-
lowing table represents the composition of the blood in a
healthy adult male (the author):

COMPOSITION OF THE BLOOD*

Globules 495 . 59

r Water 1 5 5 • 42

p, I Fibrin 8.82

i-lasma. • Albumin 329.82

1 Fats, inorganic salts, and extractives (B. & R.). 10.35

1,000.00

Physiologists have not yet sufficient data to arrive at
any definite conclusions in regard to variations in the
organic constituents of the blood as regards sex, conditions

* Denis, " Memoire sur le sang.," Paris, 1859, p. 427.

f Milne Edwards, " Le9ons de physiologie," etc., tome i., p. 237.

X Lehmann, " Physiological Chemistry," American edition, vol i., p. 548.

* In order to ascertain whether this specimen of blood contained what would
be considered as the normal quantity of organic constituents estimated by the
old method, these were evaporated to dryness and carefully weighed, with the
following result, which it will be seen corresponds with that generally obtained :

Fibrin 2.50 parts per 1 ,000.

Albumin 71-53 " "

Globules 125.00 " "

The proportion of albumin in the serum was 82.07.

ORGANIC NITROGENOUS PRINCIPLES 313

of the system and in different animals, which considera-
tions, indeed, would be beyond the scope of this paper; but
the few facts I have collected go to confirm some of the
■observations which have already been made upon these
points. It has been often observed that the blood of the ox
is much richer in fibrin than that of the human subject; the
former containing- 5 to 6 parts per 1,000 dry, while the latter
contains but 2 or 3. This difference is shown in the pre-
ceding analyses, where the blood of the ox is found to con-
tain 14.52 to 16.27 parts of moist fibrin, human blood con-
taining but 8.82 parts. The analyses also show a greater
quantity of fibrin in the two specimens of blood of the fe-
male than in the blood of the male. In the observations of
■others, the quantity has not been found to vary much in
the sexes. In this instance, neither of the specimens from
the female can be taken as perfectly normal ; as in Examina-
tion III. the subject was plethoric, and in Examination IV.
she had been taking sulphate of magnesia and was some-
what anemic.

The albumin was found to vary considerably in the
specimens of human blood, being more abundant in the
blood of the male in Examination I. than in the female
in Examinations III. and IV.. but less in the blood of the
male in Examination II. than in the female in Examina-
tion III. There are not here sufficient data to lead to
any conclusion in regard to the variations of albumin in
the sexes. In the blood of the ox the albumin was much
less than in human blood.

The quantity of globules was found to be greater in the
male than in the female. This has been noticed by all ob-
servers who have directed their attention to this point, and
is, perhaps, one of the most characteristic of the differences
between the blood of the male and of the female. One of
the females was slightly plethoric, which caused the glob-
ules to mount up nearly to the standard in the healthy
male. This condition of plethora, according to Andral,
is dependent almost entirely upon an increase in the glob-
ules. The difference in this respect between the blood of
the female who was slightly plethoric, and the other, who
was somewhat anemic, is very marked; in the former the
globules are 484.51 and in the latter, 382.95. The blood of
the ox was found to be very rich in globules.

314 ORGANIC NITROGENOUS PRINCIPLES

In conclusion, I may say that I have not attempted to
settle the normal constitution of the blood, much less to
follow out the variations to which it is subject. This would
require a largely extended series of observations. But,
considering a proper idea of the condition of existence of
the organic ingredients of great importance to the physiolo-
gist and physician, I have endeavored to study this fluid
from a physiological point of view; and with the ideas I
have been led to entertain on this subject, it seemed that a
new method of analysis which would give real propor-
tions of these principles was indispensable. My object has
been merely to settle upon some rational and simple proc-
ess, leaving its extended applications to be made in the
future. The process I have described seems to me suffi-
ciently accurate for all practical purposes; and it is so
easy of application that I can not but indulge the hope
that others may be led to cultivate this interesting and
fruitful field of inquiry.

XIV

EXPERIMENTS UNDERTAKEN FOR THE PUR-
POSE OF RECONCILING SOME OF THE DIS-
CORDANT OBSERVATIONS ON THE GLYCO-
GENIC FUNCTION OF THE LIVER

Published in the " New York Medical Journal " for November, 1869.

When it was announced by Bernard, in 1848, that he
had discovered a new and important function of the Hver,
there being in this organ a constant production of the
same variety of sugar that had long been recognized in
the urine of diabetic patients, the great physiological and
pathological importance of the discovery, attested, as it
was, by experiments which seemed to be absolutely con-
clusive in their results, excited the most profound scientific
interest. During the present century, indeed, there have
been few physiological questions which have attracted so
much attention; and the observations of Bernard were
soon repeated, modified and extended by experimentalists
in different parts of the world. In 1857 Bernard discov-
ered a sugar-forming material in the liver, analogous in
its composition and properties to starch; and this seemed
to complete the history of glycogenesis.

I do not propose at this time to give an extended re-
view of the experiments which have been made in different
parts of the world with the view either of confirming or
overthrowing the theory advanced by Bernard, but shall
discuss the two opinions wdiich are now most prevalent in
English and French physiological literature. These two
opinions are the following:

Those who accept the experiments of Bernard as con-
clusive assume that the substance of the liver and the blood
in the hepatic veins always contain sugar. This sugar is
believed to be formed in the so-called hepatic cells, from

315

3i6 GLYCOGENIC FUNCTION OF THE LIVER

the glycogen contained in them, and to be taken up by
the blood as it passes through the liver, existing in the
hepatic veins, the ascending vena cava and the right side
of the heart. It usually disappears from the blood in its
passage through the lungs. Sugar is believed always to
exist in the liver, the blood of the hepatic veins and of the
right side of the heart, independently of the kind of food
used. In the carnivora the blood of the portal system
never contains sugar when the animal is confined to a diet
of nitrogenous and fatty matters; but sugar is found none
the less invariably in the liver and in the vascular system
between this organ and the heart.

Others have accepted the view advanced by Dr. Pavy,
of Guy's Hospital, w'ho professes to have demonstrated
that neither the liver nor the blood circulating between the
liver and the heart ever contains sugar during life; but
that the sugar which has been found in these situations
is the result of a post-mortem change of the glycogenic
matter, or as it is called by Dr. Pavy, the amyloid matter
of the liver.

These two opposite views are supported by experiments
which seem to be conclusive; yet it is evident that, if the
observations in both instances are entirely accurate, they
must prove precisely the same fact. It was in the hope of
harmonizing these discordant opinions, that I undertook
some modifications of the experiments of Bernard and
Pavy. I shall not discuss the accuracy of the methods
employed by these observers but intend merely to follow
out a train of reasoning, which seems to me to be fully
sustained by experiment and which I believe will lead to
a correct interpretation of the apparently opposite results
heretofore obtained.

Since the summer of 1858 I have been in the habit
of repeating, several times each year, the experiments by
which Bernard demonstrated the glycogenic function of
the liver, performing the experiments chiefly as class-
demonstrations. I have followed most of the modifica-
tions of these experiments which have been published by
Bernard from time to time and I have almost always con-
firmed his results in every particular. I have never failed
to demonstrate the absence of sugar in the blood of the
portal system, when the specimens were taken with proper

GLYCOGENIC FUNCTION OF THE LIVER 317

precautions from carnivorous animals that had taken
neither starch nor sugar into the ahmentary canal. I have
found it important to apply a hgature rapidly to the portal
vein as it penetrates the liver and to make a very small
opening into the abdominal cavity in this step of the ex-
periment. When I have detected a trace of sugar in the
clear extract from the portal blood of an animal in the
condition just mentioned, it has been consequent upon
delay in seizing the vein; and I have anticipated the prob-
ability of finding sugar from blood, which, under these
circumstances, regurgitates from the liver. The necessity
of employing these precautions is fully insisted upon by
Bernard. I have never failed to find sugar in the blood
of the hepatic veins of healthy dogs that had taken neither
starch nor sugar into the alimentary canal. In my earlier
experiments I never failed to find a great abundance of
sugar in the substance of the liver, in dogs under the
same conditions. In one instance, however, in the winter
of i859-'6o, I failed to find sugar in the liver of a dog that
was affected with what is known as "mange"; but I
considered this to be due to the peculiar condition of
the animal.

On several occasions I have repeated Bernard's experi-
ment of analyzing for sugar, the portal blood, the sub-
stance of the liver, the hepatic blood, the blood from the
right side of the heart, the substance of the lungs, the blood
from the arterial system, and the substance of the muscles,
the kidneys and the spleen, all the specimens being taken
from the same animal. I have always found that sugar
existed only in the substance of the liver, the blood from
the hepatic veins, and the right side of the heart and in no
other situations; showing, apparently, that sugar is con-
stantly being produced by the liver and is carried by the
circulating blood to the lungs, there to be destroyed.
On several occasions I have drawn the blood from the
right side of the heart of a living animal, by catheteriza-
tion through an opening into the right external jugular
vein (a manipulation which presents no difficulty), and
have never failed to find sugar. This experiment I have
done without the administration of ether, following the
operative procedure described by Bernard.

I have also frequently repeated the experiment of pgss-

3i8 GLYCOGENIC FUNCTION OF THE LIVER

ing a stream of water through the Hver from the portal
vein, by which all the sugar can be removed in a short
time, and testing the sulistance of the Hver a few hours
after, it having been kept in the mean time at a tempera-
ture of 80° to 100° Fahr. In this experiment I have al-
ways found an abundance of sugar. The glycogen out
of which this secondary formation of sugar is supposed to
take place, I have extracted and studied after the method
proposed by Bernard and have confirmed his observations
on this substance in every particular.

In these experiments I have used the various copper
tests; viz., Trommer's, Barreswill's and Fehling's, and have
made my clear extracts, generally by boiling with an ex-
cess of sulphate of soda, but very often by mixing the
blood or the watery extracts of the tissues with animal
charcoal and filtering.

The theory advanced by Pavy, that sugar is not pro-
duced by the liver during life and that when this substance
is found in the liver it is the result of post-mortem change
of the glycogen (which he calls the amyloid substance),
always seemed to me to be invalidated by the experiment
of catheterization of the right side of the heart in a living
animal without the administration of ether; for in the blood
taken under these conditions, the presence of sugar is un-
mistakable. The admission that sugar is contained in
the blood passing out of the liver, when ether has been
administered, and the fact that sugar is sometimes pro-
duced in the body,: in cases of diabetes mellitus (for there
are undoubted cases in which sugar is discharged in the
urine, when neither starch nor sugar has been taken as
food), point to the probable normal production and de-
struction of this substance in the economy. Sugar can
hardly be regarded as a heterologous substance or as a
product of decomposition; and it constitutes an important
article of food, from the fact that it is consumed in the
body in connection with certain of the processes of nutri-
tion.

Dr. Pavy asserts that the liver never contains sugar
during life; but that after death, it is formed out of the
amyloid substance, and its proportion goes on increas-
ing for a number of hours, particularly when the organ
is kept at about the temperature of the body. The ex-

GLYCOGENIC FUNCTION OF THE LIVER 319

periments of Bernard with a liver washed out with a
stream of water also show that sugar may be produced
after death.

I was led to perform the following experiments by the
fact that of late years, the experiments by which I have
been in the habit of demonstrating the glycogenic func-
tion of the liver have inclined me to the opinion that the
observations detailed by Dr. Pavy are entirely accurate;
and that the error consists in his interpretation of the
facts. The circumstances which led to this view were the
following:

I formerly was in the habit of making my demonstra-
tions of the formation of sugar in the liver upon animals
that had been etherized; and then I always obtained a
brilliant precipitate from a clear extract of the substance
of the liver, boiled with the test-liquid. I performed the
experiment in this way before I had acquired sufficient dex-
terity to seize the portal vein readily and to go through
with the necessary manipulations with rapidity. I subse-
quently made the operation by first suddenly breaking up
the medulla oblongata, then making a small incision into
the abdominal cavity and seizing the portal vein instantly,
following out the remaining steps of the experiment with-
out delay. In this way, although I always found sugar
in the blood of the hepatic veins, I frequently failed to
obtain a distinct reaction in the extract of the liver; and
the more accurately and rapidly the operation was per-
formed, the more difficult was it to detect sugar in the
hepatic substance.

It occurred to me, in reflecting upon these facts, that
inasmuch as no one has assumed that the actual quantity
of sugar produced by the liver is very considerable, and
as a large quantity of blood (in which the sugar is very
soluble) is constantly passing through the organ, precise-
ly as water is passed through its vessels to wash out the
sugar, the sugar might be washed out by the blood as
fast as it is formed; and really the liver might never con-
tain sugar in its substance, as a physiological condition,
although it is constantly engaged in its production. It
is well known that the characteristic elements of the vari-
ous secretions proper are produced in the substance of the
glands and are washed out at the proper time by liquid

320 GLYCOGENIC FUNCTION OF THE LIVER

derived from the blood, which circulates in the g^lands dur-
ing their functional activity in very much greater quantity
than during the intervals of secretion. The liver-sugar may
be regarded as an element of secretion; and possibly it
may be completely washed out of the liver, as fast as it
is formed, by the current of blood, the hepatic vein, in this
regard, serving as an excretory duct.

To put this hypothesis to the test of experiment, it
was necessary to obtain and analyze the liver in a con-
dition as near as possible to that under which it exists in
the living organism; and in carrying out this idea, I made
the following experiments:

Experiment I. — A medium-sized dog, full grown, in good con-
dition and not in digestion was held upon the operating-table by
two assistants and the abdomen was widely opened by a single
sweep of the knife. A portion of the liver, weighing about two
ounces, was then cut off and immediately cut into small pieces,
which were allowed to fall into boiling water. The time from the
first incision until the liver was in the boiling water was twenty-
eight seconds. An excess of crystalHzed sulphate of soda was
then added, and the mixture was boiled for about five minutes. It
was then thrown upon a filter and the clear fluid which passed
through was tested for sugar by Trommer's test. The reaction
was doubtful and presented no marked evidence of sugar.

Experiment II. — A medium-sized dog, in the same condition
as the animal in the first experiment, was held upon the table and
a portion of the liver excised as above described. The whole oper-
ation occupied twenty-two seconds. But ten seconds elapsed from
the time the portion of the liver was cut off until it was in the
boiling water. It was boiled for about fifteen minutes, made into
a paste with animal charcoal and thrown upon a filter. The clear
fluid which passed through was tested for sugar by Trommer's
test. There was no marked evidence of sugar.

Experiment III. — A large dog, full grown and fed regularly
every day, but not in digestion at the time of the experiment, was
held firmly upon the table. This dog had been in the laboratory
about a week and was in a perfectly normal condition. The ab-
dominal cavity was opened and a piece of the liver was cut off and
thrown into boiling water, the time occupied in the process being
ten seconds. Before the liver was cut up into the boiling water,
the blood was rinsed off in cold water. The liver was boiled for
about seventeen minutes, mixed with animal charcoal and the
whole thrown upon a filter.

Immediately after cutting off a portion of the liver and throw-
ing it into boiling water, the medulla oblongata was broken up;
a ligature was applied to the ascending vena cava just above the
renal veins ; the chest was opened, and a ligature was applied ta
the vena cava just above the opening of the hepatic veins. A

GLYCOGENIC FUNCTION OF THE LIVER 321

specimen of blood was then taken from the hepatic veins. This
part of the operation occupied not more than one minute. A
little water was added to the blood, which was boiled briskly, mixed
with animal charcoal and thrown upon a filter. The liquids which
passed through from both specimens were perfectly clear.

While the filtration was going on, Fehling's test liquid (a mix-
ture of sulphate of copper, neutral tartrate of potash and caustic
soda) was made up, so as to be perfectly fresh.

The two liquids were then carefully tested for sugar with this
solution. The extract of the liver presented not the slightest trace
of sugar. The extract from the blood of the hepatic veins pre-
sented a well-marked deposit of the oxide of copper, revealing
unequivocally the presence of a small quantity of sugar.

In these experiments I did not attempt to show the
absence of sngar in the l)lood of the portal system; for it
would have been difficult, if not impossible, to have de-
monstrated this and at the same time to have obtained
the specimens of liver as rapidly as I desired. The fact
that the portal blood in a carnivorous animal that has
taken no saccharine or starchy matters into the alimen-
tary canal contains no sugar. I regarded as settled by the
experiments of Bernard, which I have repeatedly con-
firmed. Neither did I attempt to show^ that sugar exists
in the liver when a certain period has elapsed after death;
for this fact has been demonstrated by all who have ex-
perimented on the subject. I desired only to ascertain
whether the liver taken from a living animal, and the
change of the glycogen arrested before any sugar has had
time to make its appearance, if its formation is post mor-
tem, really contained sugar. A few seconds only elapsed
before the liver was cut up into boiling water (which will
effectually arrest the transformation of the glycogenic
matter), and the presence of sugar in the decolorized ex-
tract could not be demonstrated. In Experiment III. par-
ticularly, very delicate tests were employed with the great-
est care; and although the extract of the liver contained
no sugar, the presence of sugar in the blood coming from
the liver w^as unmistakable. This experiment was pecul-
iarly successful; and I could hardly expect to be able to
collect the specimens with less delay. Anesthetics were
not employed in any of the experiments, and there seemed
to be no circimistance that could interfere with the normal
character of the specimens examined. The animals were
perfectly quiet when the experiments were begun, and

322 GLYCOGENIC FUNCTION OF THE LIVER

they were operated upon as soon as they were put upon
the table, the respiration and circulation being apparently
normal.

CONCLUSIONS

Although these experiments are not entirely new, my
interpretation of them serves to harmonize, in my owai
mind at least, the results obtained by Bernard and by
Pavy :

L A substance exists in the healthy liver, which is
capable of being converted into sugar; and inasmuch as
this is changed into sugar during life, the sugar being
washed away by the blood passing through the liver, it
is proper to call it glycogen, or sugar-forming matter.

IL The liver has a glycogenic function, which consists
in the constant formation of sugar out of the glycogen,
this sugar being carried away by the blood of the hepatic
veins, which always contains a certain proportion of sugar,
and subserving some purpose in the economy connected
with nutrition, as yet imperfectly understood. This pro-
duction of sugar takes place in the carnivora as well as
in those animals that take sugar and starch as food; and
it is essentially independent of the kind of food taken.

in. During life the liver contains only the glycogen
and no sugar, because the great mass of blood which is
constantly passing through this organ washes out the su-
gar as fast as it is formed; but after death or when the cir-
culation is interfered with, the transformation of glycogen
into sugar goes on; the sugar is not removed under these
conditions, and can then be detected in the substance of
the liver.

XV

THE TREATMENT OF DIABETES MELLITUS *

Published in the "Journal of the American Medical Association"
for July 12, 1884.

It would not be possible, within the Hmits to which this
paper is necessarily restricted, to discuss satisfactorily the
pathology or even the clinical history of diabetes mellitus,
although the disease in question is one of the most interest-
ing as well as obscure affections which the physician is
called upon to treat. While the study of diabetes and of its
attendant disorders of general nutrition presents difficulties,
as regards questions of causation and pathology, that seem
almost insurmountable, when attention is once directed to
the simple problem of the presence of sugar in the urine,
this condition is now easily and certainly recognizable. It
is probably true that sugar exists in the urine of a certain
number of persons, unattended with symptoms, so that it is
detected only by accident or may never be revealed, such
persons having no apparent occasion to seek medical ad-
vice. In an experience in life insurance examinations ex-
tending through a period of nearly thirteen years, I have
found a small quantity of sugar in the urine of applicants
who supposed themselves to be perfectly healthy; but with-
in the time mentioned, only five such cases have come
under my observation. Three of these applicants are now
living and are presumably in good health, the sugar in the
urine having been noted eight to twelve years ago; one
case was lost sight of and one applicant is reported to
have died of hemoptysis nine months after the examina-
tion of the urine. During the time mentioned; viz.. twelve
years and nine months. I examined 1,884 persons who sup-
posed themselves to be in good health and nearly always

* Read in the Section on Practice of Medicine and Materia Medica of the
American Medical Association, in May, 1884.

323

324 TREATMENT OF DIABETES MELLITUS

made examinations of the urine. All of the applicants, with
one or two exceptions, were males. The proportion, there-
fore, of apparently healthy persons in whose urine I have
found sugar is very small (i in 377); but even this shows
that sugar may be present in the urine, either as a transient
or an insignificant condition or existing without any of the
general symptoms of diabetes.

In the great proportion of cases of diabetes that come
under observation, attention has been directed to the con-
dition of the urine by certain general symptoms, such as
excessive thirst, persistent polyuria, a sensation of dryness
of the mouth and fauces, fatigue after moderate muscular
exertion or some slight affection of the external genitals.
In a case of diabetes that I have had under treatment for
nearly four years, now under observation, the patient first
consulted a physician for herpes progenitalis, which led to
an examination of the urine. In females, persistent pruritus
of the vulva is often the first trouble pointing to the possi-
ble existence of diabetes. In several cases I have detected
sugar in the urine when pruritus vulvae was the only trouble
complained of by patients. So constant is this symptom^
that diabetes should always be suspected when the pruritus
persists without any apparent cause and resists ordinary
measures of treatment. The pruritus is seldom absent when
the proportion of sugar in the urine is considerable.

Detection of Sugar in the Urine. — So far as purely
clinical examination of the urine is concerned, the great
desideratum is a simple test, easy and rapid in its appli-
cation, upon which one can rely with absolute confidence.
I shall pass over, without discussion or even mention, the
different tests employed for the detection of sugar, except
the one known as Fehling's. When the Fehling's liquid is
properly prepared and carefully used, there can be no error
in the results. If a quantity of this test, however, be made
and kept for some time, it is liable to change so as to be-
come more or less unreliable. This want of stability in the
test-liquid has long been recognized by those accustomed
to urinary examinations; and a few years ago I prepared
three separate liquids, which I mixed in certain proportions
for use as required. Even this did not prove to be entirely
satisfactory. Within the last year, two separate liquids have
been prepared by Dr. E. R. Squibb, and are kept by him

TREATMENT OF DIABETES MELLITUS 325

for sale, in which form the test seems to leave nothing to
be desired in the qualities of accuracy and ease of applica-
tion. The test, as it is now prepared by Dr. Squibb, is
simply perfect; but so much depends upon its proper use,
that I venture to give an account of its application and the
necessary precautions to be adopted. These precautions
are simple and demand no special skill; but they often be-
come very important, especially in determining with cer-
tainty the absence of sugar.

The two test-liquids are prepared by Dr. Squibb accord-
ing to the following formulas:

For the Solution of Cupric Sulphate. — Use puri-
fied sulphate of copper, in granular crystals, air-dried.
Weigh 2^^ grains (17.32 grammes) of the salt and dissolve
it in about 4 fluidounces (120 cc.) of distilled water, adding
about 4 minims {\ cc.) of pure sulphuric acid. /\dd dis-
tilled water to this solution to make 8^ fluidounces (260
cc).

For the Solution of Alkaline Tartrates. — Weigh
2 ounces, 391 grains (87.5 grammes) of re-crystallized
sodio-potassic tartrate, or Rochelle salt, and dissolve it in
about 6 fluidounces (175 cc.) of distilled water. Filter the
solution, if necessary, and add it to a clear solution of 386
grains (25 grammes) of caustic soda in about if fluidounces
(50 cc.) of distilled water. Add distilled water to this
solution to make %\ fluidounces (260 cc).

These two solutions are to be kept in separate bottles
for use. If they are made with accuracy and mixed together
in equal proportions, two hundred grains of the mixture
will be decolorized by exactly one grain of sugar, or each
cubic centimetre of the mixture will be decolorized by 0.005
of a gramme of sugar. The liquids can therefore be em-
ployed for quantitative estimates, although I shall describe
the use of the test simply for determining the fact of the
presence or absence of sugar.

For use in qualitative analysis, the two liquids may be
roughly mixed in about equal proportions in a test-tube or
they may be measured accurately and diluted with about an
equal volume of distilled water. The latter process should
be resorted to in all delicate analyses.

For ordinary use the following process may be em-
ployed:

326 TREATMENT OF DIABETES MELLITUS

Mix in a test-tube equal volumes of the two li(|uids so
that the mixture will extend in the tul)e to the length of
about an inch.

Bring the mixture to the boiling point and then add to
the boiling test a quantity of urine e([ual to that of the test.

Bring the mixture of the test-liquid and urine to the
boiling point and then allow it to cool.

If no distinct and opaque reddish or yellowish precipi-
tate is present when the mixture of test and urine has be-
come cool after the second boiling, it is certain that no sugar
is present.

All these precautions are essential; and I have repeat-
edly examined specimens of urine in which the character-
istic precipitate due to the presence of sugar did not occur
until one or two minutes had elapsed after the second boil-
ing.

In very delicate testing, take a definite quantity of the
copper solution, add an equal quantity of distilled water,
add then of the solution of alkaline tartrates a quantity equal
to the cjuantity of the copper solution, and add finally dis-
tilled water in the same quantity. When this mixture is
boiled, if the test is not absolutely perfect, there will be a
precipitate before the urine is added. The mixture, if
perfect, may be used in the same way as the simple un-
diluted mixture of the two solutions.

When sugar is present in the urine, an opaque yellow-
ish or reddish precipitate appears at some time during the
process, the promptness of its appearance and its quantity
being in direct proportion to the quantity of sugar.

It is often important to be able to determine, at least
approximately, the quantity of sugar discharged in twenty-
four hours or its proportion per fluidounce. Using the
volumetric process, this estimate requires some practice
and occupies twenty to thirty minutes; but the "differ-
ential density method " recommended by Roberts, is very
simple and is sufficiently accurate for ordinary purposes.
With a little practice, indeed, it may be employed by in-
telligent patients.

Two specimens of diabetic urine are taken, about four
ounces of each, one for comparison and the other for anal-
ysis. To one is added a lump of German yeast, about the
size of a filbert, in a bottle with a cork nicked to allow^ the

TREATMENT OF DIABETES MELLITUS 327

escape of gas; and the other specimen is placed in a similar
bottle tightly corked. The bottles are then put aside in a
warm place, as the mantelpiece in winter or in the sun in
summer. In the course of twenty-four hours, fermentation
will have been completed in the specimen to which yeast has
been added. If the specific gravity of the two specimens
is then compared, the fermented specimen will be found
much the lighter, from loss of the sugar which has been
decomposed into alcohol and carbonic acid. The differ-
ence in the density of the two specimens, expressed in de-
grees of the urinometer, will represent the number of grains
of sugar per fluidounce in the urine. For example, if the
specific gravity of the fermented specimen is loio, and the
specific gravity of the unfermented specimen, 1040, the
urine contains thirty grains of sugar per fluidounce. In
this process it is essential to compare the density of the two
specimens at the same temperature. If German yeast can
not be obtained readily, about a teaspoonful of ordinary
baker's or brewer's yeast may be used.

Relations of the Specific Gravity of Urixe to
THE Proportion of Sugar. — It has long been recognized
that the specific gravity of the urine bears no definite and
constant relation to the proportion of sugar in cases of dia-
betes. In a case that came under my observation in Decem-
ber, 1883 and has been under treatment until the time of
writing (April, 1884) on Dec. 29, 1883. the specific gravity
was 1038, with 28.4 grains of sugar per fluidounce. The
next day. the specific gravity was 1036 and the proportion
of sugar was 9 grains per fluidounce. In another very
interesting case now under treatment, I found 4 grains
of sugar per fluidounce, the urine having a specific gravity
of only loii^. These remarkable variations in the spe-
cific gravity, occurring without any relation to the quan-
tity of sugar, are generally dependent upon the propor-
tion of urea, the absolute quantity of which is often very
largely increased in cases of diabetes. I have often found
crystals of uric acid as a persistent condition in diabetic
urine, sometimes associated with a deposit of oxalate
of lime.

The time allotted to me does not permit a discussion of
the possible relations of the nutritive conditions connected
with diabetes to the excessive elimination of urea or th-^

328 TREATMENT OF DIABETES MELLITUS

frccjiicnt presence of crystals of uric acid; but it is very im-
portant to remember that urine of a comparatively low
specific gravity may contain sugar. Within a week, in
another case in which the urine is examined every three or
four days, I found a marked sugar-reaction in a specimen
of urine with a specific gravity of loii. I have also re-
peatedly found sugar in urine of a specific gravity of about
1 020, the quantity of urine in twenty-four hours being
normal. The fact, then, that the quantity and specific
gravity of the urine are normal does not in itself exclude
sugar; although, in most cases of diabetes, the quantity
of urine is increased and its specific gravity is notably high.
In a case of dialjetes very minutely reported by Pavy, sugar
was found in the urine when the specific gravity of the
specimens was, on different occasions, loio, loii, 1012
and 10 1 3.* In cases in which diabetes is suspected, the
physician is not justified in excluding the disease when he
finds no increase in the quantity of urine and a normal spe-
cific gravity; and the facts just mentioned show that in all
cases of this kind the urine should be carefully tested for
sugar.

What constitutes Diabetes Mellitus? — A patient
with abnormal thirst, dryness of the mouth, suffering from
fatigue following slight muscular exertion, progressively
losing strength and weight and passing an abnormally large
quantity of urine of high specific gravity and containing
sugar has the disease known as diabetes mellitus; but the
various symptoms just enumerated may exist in greater or
less degree or some of them may be absent. In addition to
these symptoms, others may exist ; such as, abnormal dry-
ness of the skin, deficient perspiration on exercise or in
"warm weather, pruritus of the vulva, a tendency to furun-
cles, unusual lial^ility to " take cold," refluction in the gen-
eral temperature of the body, an excessive appetite, failure
of the generative functions, etc., but these are not neces-
sarily present in cases of diabetes.

On the other hand, none of the general symptoms that
I have mentioned may be observed; the urine may be nor-
mal as regards quantity and specific gravity; but still sugar
may exist constantly in small quantity. In such instances,

* Pavy, " Nature and Treatment of Diabetes," London, 1869, p. 28S.

TREATMENT OF DIABETES MELLITUS 329

which are not infrequently observed, the constant, neces-
sary and invariable symptom of diabetes is present; namely,
glycosuria. Strictly speaking, perhaps, patients with no
general symptoms, with no increase in the quantity of urine
and with urine of normal specific gravity may be said to be
affected with glycosuria, but not to have diabetes. In the
great majority of cases, however, unless the glycosuria is
transient and dependent upon some recognizable or tem-
porary cause, certain of the general symptoms of diabetes
will sooner or later become developed, unless the glycosuria
is relieved by treatment. Still, even without treatment,
persons may live in what seems to be perfect health for
years, constantly passing considerable quantities of sugar.
I can now call to mind three cases of this kind; and several
cases, in which I have found sugar in the urine without any
other diabetic symptoms, have passed from under my ob-
servation.

I shall have little to say concerning the etiology and
pathology of diabetes. The physiological experiments,
which began with the discovery of the sugar-producing
function of the liver by Claude Bernard, in 1848, have failed,
in a great measure, to fulfil the expectation that they would
lead to a full comprehension of the pathology of this
disease. I believe it to be true that the liver is a sugar-pro-
ducing organ. The experiments of Pavy, in which he
showed that the liver-substance does not actually contain
sugar during life were, in my opinion, harmonized with
those of Bernard, by experiments made by me in 1869.*
In these experiments, I found no sugar in an extract of the
liver taken from a living dog and put into boiling water in
ten seconds, while sugar was present in blood taken from
the hepatic veins. I am convinced that the liver is con-
stantly forming sugar during life; but that this sugar, as fast
as it is produced, is washed out of the sugar-producing
organ by the blood-current. Experiments have shown,
also, that the sugar contained in the food as well as that
resulting from the digestion of starch is destroyed in the or-
ganism. That the sugar-forming function of the liver may
become exaggerated beyond the power of the organism to

* " Experiments undertaken for the Purpose of reconciling some of the Dis-
cordant Observations upon the Glycogenic Function of the Liver." — " New
"York Medical Journal," 1S69, vol. viii., p. 373 et seq.
22

330 TREATMENT OF DIABETES MELLITUS

destroy the excess thus formed was demonstrated by the
remarka1)le experiments of Bernard, in which he produced
temporary glycosuria in animals by mechanical irritation of
the floor of the fourth ventricle, by stimulating the pneu-
mogastric nerves or by introducing irritating vapors into
the lungs; but although cases of traumatic diabetes occur
in the human subject, they are exceedingly rare. No such
case has yet come under my observation.

I do not propose, at this time at least, to offer any
theory in regard to the causation or pathology of diabetes,
the cause of death in the so-called diabetic coma or the sup-
posed development, in certain cases, of acetonemia. The
discussion of these points has, up to the present time, been
very unsatisfactory. It is well known that patients pre-
senting in a well-marked degree certain characteristic symp-
toms, in addition to glycosuria, are affected with a very
grave disease, the pathology of which is imperfectly under-
stood. The sugar resulting from digestion is in great part
discharged in the urine. The nutritive processes are seri-
ously disturbed. The power of resistance to other diseases
is impaired; and what is remarkable and quite interesting
in its relations to our ideas of the production of animal heat,
the failure to consume the carbohydrates seriously affects
the power of resistance to cold, and the general temperature
of the body is habitually 95° or 96° Fahr., instead of about
98^°. This latter point I state upon the authority of many
writers; and in a case now under treatment, the tempera-
ture in the axilla hag constantly been about 96^°. As the
patient improved, the temperature was increased to a frac-
tion above 97°, but it has not yet reached the normal
standard.

Being brought, then, face to face with a disease, very
obscure in its pathology and not infrequent in its occur-
rence, the practical question, to which I intended to devote
the main part of this paper, is how far it is amenable to
treatment. To this question I shall devote what remains
of the time at my disposal.

Treatment. — Tn a course of lectures by Cantani, deliv-
ered at the clinical hospital of the University of Naples, in
the spring of 1872, there occurs the following statement,
italicized by the author:

" Diabetes has become to-day a disease easily and cer-

TREATMENT OF DIABETES MELLITUS 331

taiiily curable, provided that the treatment (cure) is noi
begun too late." *

The cases which Cantani details in support of this rather
startling statement show certainly most remarkable ef-
fects of treatment. Judging from the account of these
cases, the general proposition that diabetes is a disease in
the main easily and certainly curable is not too decided and
absolute. Since I have been engaged in treating cases of
this disease, my experience, though not extending over
many years, has led me to the conviction that the claim
made by Cantani is not entirely extravagant.

In the great majority of cases in which patients will sub-
mit to certain measures of treatment so soon as it is estab-
lished that they are suffering from diabetes, or so soon as
glycosuria is recognized, it is possible to effect either a cure
of the disease or a removal of most of the characteristic
svmptoms, with the exception, perhaps, of the occasional
appearance of a small quantity of sugar in the urine.

Time does not permit me to discuss fully the treatment
recommended by different writers. Cantani relies mainly
upon dietetic measures, although he attaches considerable
importance to the exhibition of lactic acid and the alkaline
lactates. Of course the treatment by eliminating sugar and
starch from the diet is by no means novel. Dating from
the time of Rollo, it has had the earnest support of Bou-
chardat, Pavy, Seegen and many others. I desire to state
at the outset, that the main and almost the sole reliance of
the physician should be upon diet; and that the suppression
of starch and sugar should be nearly absolute. Bearing this
constantly in mind, in considering the different measures
of treatment I shall divide them into dietetic, general, and
medicinal.

Dietetic Treatment. — In 1869, a patient was sent to
me from Omaha, Neb., whpm I found to be suffering from
many of the distressing symptoms of diabetes.

On November 20, 1869 he passed 224 fluidounces of
urine in the twenty-four hours, with a specific gravity of
1035. The quantity of sugar passed in the twenty-four
hours was 18 ounces and 30 grains, and the quantity of
urea was 624 grains. I recommended a diet-table by no

* Cantani, "Le diabete Sucre et son traitement diet€tique," Paris, 1876, p. 386.

332 TREATMENT OF DIABETES MELLITUS

means so rigid as the one I now employ, and he left for
home. For several years I heard from this patient, either
personally or through his physician in Omaha, from time
to time, and he was reported as apparently well but occa-
sionally passing a small quantity of sugar. He continued
the diet more or less faithfully for two or three years but
took a little bread. About live years after, I was accosted
in the street by this patient, who reported himself as feel-
ing perfectly well and giving but little attention to his
diet. At this time I did not have an opportunity of exam-
ining the urine. The patient has since died; and I heard
from his widow that this occurred in August, 1881, his
death being immediately due to inflammation of the bowels
after a few days' illness. '' The diabetes was much im-
proved and troubled him very little."

This case, during the time when I was constantly re-
ceiving favorable reports, seemed to me to be quite remark-
able; and in 1880, having frequent occasion to recommend
a diet for diabetics, I carefully compiled an antidiabetic
diet-table, which I have since used constantly in cases that
have come under my observation and which I shall present
as an appendix to this paper. In preparing this table, my
object has been to secure a diet sufficiently nutritious but
free from starch and sugar, using as a basis the admirable
list given by Bouchardat; '•' and I have endeavored to adapt
the articles and their preparation to the customs of our own
country, adding to it, when possible, in order to secure the
greatest available variety of food. Selecting, however,
every dish known in the culinary art, without reference to
the trouble or expense of its preparation, a rigid diet is by
no means easy of enforcement. Patients at first have an
intense craving for bread; and this desire is so nearly uni-
versal that almost all writers on diabetes suggest some sub-
stitute for this important article pf food. I do not hesitate
to say, however, without specifying any one of the so-
called antidiabetic breads and flours as especially bad,
that all the articles of this kind in our markets are un-
reliable and most of them fraudulent. I have analyzed,
or caused to be analyzed, nearly all of the so-called
bran-flours and gluten-flours and have invariably found

* Bouchardat, " De la glycosurie ou diabete sucre," Pans, 1875, p. clxxxvi

TREATMENT OF DIABETES MELLITUS 333

large quantities of starch. Two specimens said to be
free from starch, which were analyzed with great care by
a competent chemist, were found to contain a greater pro-
portion than exists in ordinary wheat-flour. Most of the
so-called diabetic breads are pasty, heavy and become ex-
tremely distasteful. A patient now under occasional ob-
servation, having procured a new bread w-hich was so agree-
able to the taste that he took it freely and with relish, im-
agined that he had found at last an article which would be
regarded by diabetics as the greatest boon. This bread was
made of flour which contained aljout 80 per cent, of starch.*
The effects of this fraud upon the patient were quite serious.
His health had become nearly restored and the sugar had
disappeared from the urine. Under the use of the bread
the sugar returned and it was several weeks before it dis-
appeared again under a strict diet. In the rigid dietetic
treatment bread should be absolutely interdicted; or in
case patients should refuse to submit to a strict diet, a
small quantity of crust of bread taken with an abundance
of butter may be allowed.

A rigid diet, without bread, should be continued until
the sugar has disappeared from the urine and all the diabetic
symptoms have disappeared. Although many diabetics
rebel under this regimen and the execution of this measure
demands on their part much self-denial and fortitude, pa-
tients may be encouraged to persevere, by the statement
that the craving for saccharine and starchy articles is likely
to diminish and may almost disappear after a few weeks.
I have now under observation and treatment several pa-
tients who have actually lost all desire for most of the inter-
dicted articles of food.

In cases in which the treatment is followed by an appar-
ent cure, sugar no longer existing in the urine, a gradual re-
turn to the normal diet should be begun about two months
after the glycosuria has disappeared ; but it is of the greatest
importance during this part of the treatment to keep pa-
tients, if possible, under constant observation, examining
the urine at least once in five or six days. When the sugar
disappears, patients may regard themselves as permanent-
ly cured and no general symptoms present themselves for

* Ordinary wheaten flour contains about 70 per cent, of starchy matters.

334 TREATMENT OF DIABETES MELLITUS

some time after glycosuria has returned vmder a mixed
diet. Several unfortunate examples of this have come
under my observation.

General Treatment. — Measures of general treatment
are to be directed mainly to promoting the proper action
of the skin, which often is harsh and abnormally dry, and
to general muscular exercise. Systematic rubbing, as
practiced by massage, and Turkish or Russian baths once
a week, if not contraindicated by some complicating con-
ditions, are useful. A reasonable restriction in the taking
of liquids is Cjuite important in diminishing the quantity of
urine. Under dietetic treatment the excessive thirst is al-
most always relieved; but when this persists, it may often
be temporarily met, so far as dryness of the mouth is con-
cerned, by taking small pieces of ice from time to time in-
stead of drinking water. I do not know that any reliance
is to be placed upon the use of the various mineral waters
that are said to exert a curative influence on the disease.
Alcoholic stimulants are to be avoided. I have seen several
cases of diabetes in which the disease seemed to be attribu-
table to the abuse of alcohol, especially the habitual and
excessive drinking of champagne. In certain cases some
kind of alcoholic 1)everage seems to be necessary to main-
tain the vital powers. For this purpose, a fairly good,
sound claret has seemed to me to be the best form in which
alcohol may be taken. Spirits should be interdicted or
given very sparingly, and not more than a pint of claret
should be taken daily.

Patients sufifering from diabetes lose to a certain ex-
tent their capacity for sustained mental effort. They should
be cautioned, therefore, against excessive intellectual work.
Mental anxiety and " worry " over business or other affairs
exert a very unfavorable influence on the progress of the
disease. In some cases apparently cured I have noted a
return of the glycosuria which seemed to be fairly attribu-
table to mental causes. Insomnia rarely demands the use
of narcotics and usually is relieved with the other symptoms
by the antidiabetic diet.

The various minor complications that are liable to occur
can usually be overcome by appropriate treatment. Boils
are very common and they are likely to be persistent and
annoying. When the tendency to boils is very marked, the

TREATMENT OF DIABETES MELLITUS 335

sulphide of calcium is useful, although this agent does not
seem to exert a curative influence on the diabetic con-
dition. Sulphide of calcium has been recommended very
highl}' as a remedy controlling the glycosuria; but it often is
disagreeable to patients and disturbs digestion. In a few
instances in which I have employed it for a considerable
time, it has not seemed to affect the discharge of sugar, and
I regard it as useful only to combat the furuncular tendency.
It is dangerous to rely upon drugs to any extent in the treat-
ment of this disease. Patients willingly put faith in rem-
edies rather than in a rigid diet; but after all, diet is the
main and almost the only reliance in treatment.

Avery important, and perhaps the most important meas-
ure of general treatment is systematic muscular exercise,
not carried to the extent of producing excessive fatigue.
This may be taken in the form of gymnastics or of outdoor
exercise, such as riding or athletic sports; but patients
should always be cautioned to avoid " taking cold." If a
patient suffering from diabetes can be made to develop
his muscular strength by moderate and systematic exer-
cise, not too prolonged and followed by a proper and not
excessive sense of fatigue and some perspiration, with a
good reaction after bathing and rubbing, much will be
gained. This is strongly recommended by all writers upon
diabetes.

The diminished power of resistance to cold which exists
nearly always in diabetics renders it necessary to enjoin
great care to avoid exposure to the vicissitudes of the
weather, and the constant protection of the body by warm
clothing, especially flannels next the skin.

Medicinal Treatment. — There is no remedy that
exerts a curative influence over diabetes in the absence of
proper dietetic measures. Opium, the bromides, sulphide
of calcium, various mineral waters and other medicinal
agents that have been recommended from time to time have
all proved unsatisfactory in practice. Of course it is dififi-
cult to estimate the value of drugs in this as in many other
diseases, particularly as the physician is not justified, in my
opinion, in neglecting to enforce a rigid diet which in itself,
in the great majority of cases, exerts a decided influence
over the glycosuria and the general symptoms. On the-
oretical grounds, Cantani recommends lactic acid, taken in

336 TREATMENT OF DIABETES MELLITUS

the form of a '' lemonade," in small quantities throughout
the day. The formula for this mixture is the following:

Pure lactic acid 3 iss to 3 v.

Aromatic water 3 v to ^ j.

Water. , Oij.

This remedy is regarded by Cantani as useful in many
cases but not essential. I have little experience in its use.

Keeping in mind the small reliance to be placed on the
efificacy of drugs not conjoined with dietetic measures, I
must bear testimony to the apparent advantage to be de-
rived from the use of the bromide of arsenic, recently pro-
posed by Clemens. While I have not felt justified in using
this remedy to the exclusion of an antidiabetic diet, for the
reason that the bad effects of an unrestricted diet frequently
persist for some time, I have noted very marked effects
from Clemens' solution in controlling the discharge of
sugar and some of the distressing symptoms, particularly
the excessive thirst ; so that, aside from simple measures to
relieve sleeplessness, constipation or other intercurrent dififi-
culties, I have lately been in the habit of prescribing, in ad-
dition to the diet, three drops of Clemens' solution, three
times daily, in a wine-glass of water after each meal, gradu-
ally increasing the dose to five drops. The following is the
formula for this remedy:

" Liquor brom-arsen consists simply of a chemical
union of arsenious acid and bromine, dissolved in water
and glycerin, in such a manner that two drops represent
the twenty-fourth part of a grain of arsenite of bromine."*

In a case of diabetes of more than five years' standing,
now under treatment, the patient has been taking Clemens''
solution constantly, with the exception of a single week,
from Dec. 2'/, 1882 to April 2, 1884, more than fifteen
months, without unpleasant effects. I began with a dose
of two drops three times daily, gradually increased to five
drops. On May 13, 1883, the urine having been free from
sugar with the exception of a trace on two or three occa-
sions for thirteen weeks, I stopped the bromide of arsenic
for one week, the antidiabetic diet being continued. At
the end of the week sugar was found in large quantity in
the urine. The use of the bromide of arsenic was then re-

* " Medical Times," Philadelphia, Dec. 2, 1882, p. 160.

TREATMENT OF DIABETES MELLITUS 337

sumed. At the end of the first week the sugar still existed
in small quantity. At the end of the second week the sugar
had disappeared and there was no return for six weeks.
The patient then left the city and committed many indiscre-
tions in diet. Seven weeks later I examined a specimen of
urine and found it loaded with sugar, with a specific gravity
of 1030. While abseiit from New York, the patient had
indulged in peas, egg-plant, stuffed tomatoes, green corn,
ice-cream, charlotte russe, peaches, raspberries, blackberries
and melons. On September 20, after returning to New
York and resuming a strict diet with the exception of the
crust of half a white roll three times daily, the patient im-
proved. The urine on September 20 had a specific gravity
of 103 1 and w-as loaded with sugar. The following week
the sugar was much diminished in quantity and it dis-
appeared at the end of the second week.

Summary of Treatment. — The more I study the cases
of diabetes that have come under my observation, especially
those that are now under treatment, in connection w4th the
writings of those who have faithfully followed the dietetic
plan, notably Bouchardat and Cantani, the more thoroughly
am I convinced that the prognosis in a recent and un-
complicated case of this disease in an adult is favorable,
provided, always, that the proper measures of treatment
are rigidly enforced. In the hone of convincing the profes-
sion that this statement is reliable, I shall, at the risk of what
may appear to be needless repetition, give a summary of
treatment, with brief statements of the progress of cases
that I am now actually observing.

At the outset patients should be impressed with the
fact that they are suffering from a grave disorder and that
everything depends upon their full cooperation in the treat-
ment, which treatment is essentially dietetic. The diet-
table should be carefully studied and the diet regulated and
carried out absolutely.

In case a rigid antidiabetic diet does not promptly in-
fluence the glycosuria, it may be well to subject a patient
to an absolute fast for twenty-four hours and follow this
with the antidiabetic regimen. This rather harsh measure
is suggested by Cantani. I shall not hesitate to employ it
in cases in which it may seem to be required, although no
such case has as yet come under my observation.

338 TREATMENT OF DIABETES MELLITUS

The various measures that I have mentioned under the
head of " General Treatment " should be enforced, es-
pecially systematic daily muscular exercise. A moderate
system of training on the plan adopted by athletes is useful;
and this, if continued, will do much to render a cure per-
manent after return to a normal diet.

The return to a normal diet should be gradual, and
(luring this time the urine should be examined frequently,
the rigid diet being resumed at the first reappearance of
sugar in the urine; but all alcoholic excesses, the immoder-
ate use of sweet fruits and any use of sugar should be inter-
dicted at all times. A patient who has once had diabetes
is always liable to a return of the disorder. He must lead
a thoroughly careful, hygienic and temperate life. In the
words of Bouchardat, " you will not be cured except on
the condition that you never believe yourself to be
cured." *

While I believe that the physician is justified in en-
couraging patients to expect relief, and even cure, in recent,
uncomplicated cases, the diet is all important; and its regu-
lation can not be expected to be perfect without profes-
sional aid in its enforcement. A diabetic is never safe from
a return of his disease, even when he believes himself to be
cured; and under no circumstances should he pass more
than a few weeks without an examination of the urine.

The bromide of arsenic, or Clemens' solution, appears
to be useful. Patients may begin with three drops three
times daily in a little water immediately after eating, grad-
ually increasing the dose to five drops. This may be con-
tinued for weeks and months without producing any un-
favorable effects; but the administration of this remedy
does not supply the place of the dietetic treatment, which
should be enforced in all cases. A rigid diet should be
continued for two months at least, even in the mildest
cases of the disease. It may be necessary in certain cases
to continue it for a longer period, even twelve or more
months.

There is probably no such disease as intermittent dia-
betes. In some instances glycosuria occurs during the sea-
son of sweet fruits, when they, are indulged in excessively,

* Bouchardat, " De la glycosuria ou diabete sucre." Paris, 1875, p. 49.

TREATMENT OF DIABETES MELLITUS 339

and disappears when the diet is changed; but these are mild
cases of diabetes, excluding those in which a transient gly-
cosuria follows the inhalation of irritating vapors, the tak-
ing of anesthetics, etc.

Robust or corpulent persons are more tolerant of the
disease than those who are feeble or spare; and the glyco-
suria yields, in such cases, more readily to treatment.

Diabetes occurs at all ages. Bouchardat mentions a
case in an infant of three years, although the disease is
rare before the age of twelve. The most unfavorable cases
are those which occur before the age of puberty. An adult
male presents the most favorable conditions for cure. In
old persons, when the disease is of long standing, the die-
tetic treatment will secure practical immunity from nearly
all the distressing symptoms, although the glycosuria may
not be entirely removed.

A study of any of the diet-tables recommended will
make it evident that those who are able to follow the re-
quired regimen, without regard to the cost of articles of
food, present much more favorable conditions, as regards
the prospect of cure, than persons in straitened or indi-
gent circumstances. Diabetes, however, occurs in all
classes and is by no means a rare disease. A hospital de-
voted to such cases, w^here the dietetic treatment could
be strictly carried out, would be a boon to the rich and
poor alike.

Cases. — I have accounts, more or less complete, of fifty
cases of diabetes. Certain of these cases have been lost
sight of; others were followed out in their histories to a
fatal termination; and tw^elve. exclusive of a few that are
reported to be cured, are still under either observation
or treatment.

Of these fifty cases, sixteen have been lost sight of. nine-
teen are either known to be living or are under observation,
and twelve have died at periods of between nine months
and twelve years after I first examined the urine.

Of the seven patients who are living but whom I do not
consider as under observation, one passes sugar constantly
and is under an imperfect antidiabetic diet, but is in w4iat
may be called fair health; two are reported as cured, al-
though I have not examined the urine for a long time; four
I simply know to be living.

340 TREATMENT OF DIABETES MELLITUS

The twelve cases that are under ol:)servation are instruct-
ive as indicating the value and influence of treatment.

Case A. — The patient, a gentleman thirty-eight years of age,
first became aware that he sutTercd from diabetes mellitus about
June I, 1883. He is five feet five inches in height and weighs one
hundred and twenty-nine pounds. A year ago he weighed one
hundred and sixty pounds. He suffered from excessive discharge
of urine, with increased appetite, thirst, dryness of the mouth, sleep-
lessness, fatigue on slight exercise, and, indeed, most of the symp-
toms of diabetes; but a careful physical examination failed to re-
veal any other disease. At the time I first saw him, he had been
taking quinine and various tonic remedies and had been subjected
to an imperfect antidiabetic diet. At this time, December 29, 1883,.
he passed eighty ounces of urine in twenty-four hours, containing
in all 3,072 grains of sugar. He was immediatelv put upon a strict
diet, taking no bread, drinking very little, and relieving the thirst
temporarily by taking pieces of ice. In addition, he took three
drops of Clemens' solution three times daily, and continued tO'
take ten grains of quinine each day. After forty-eight hours of this
treatment, his intense thirst and excessive urination disappeared;
but he expressed himself as feeling rather weak although generally
much better. The effect, however, upon the discharge of sugar was
remarkable. He passed, during the second twenty-four hours of
treatment, forty-three ounces of urine, and the total quantity of
sugar was reduced from 3,072 grains to 387 grains.

I heard from this patient January 19, 1884, and received a
specimen of the urine of the twenty-four hours of January 17th.
For the twenty days since December 29, 1883, he had maintained
an absolute antidiabetic diet, taking no bread. During this time
he took three drops of Clemens' solution three times daily. He
had gained three-quarters of a pound in weight. He had suffered
somewhat from indigestion but was otherwise quite well. " The
very large appetite and thirst are very materially lessened." The
quantity of urine in twenty-four hours was forty-eight and one-half
fluidounces ; specific gravity, 1026; absolutely no sugar; there was
rather an abundant deposit of amorphous urates with a number of
crystals of uric acid. So far as the diabetic condition is con-
cerned, the general symptoms have disappeared as well as the sugar
in the urine.

On January 25, 1884, the dose of Clemens' solution was in-
creased to five drops three times daily. The urine was free from
sugar. There was no sugar in the urine on January 27 and 29.
He was then allowed the crust of half a French roll at breakfast.

On February 4, 1884, I saw the patient again. He had been
at home and had committed some slight indiscretions in diet. The
urine had a specific gravity of 1030 and contained a small quantity
of sugar. The strict diet was resumed.

On February 10, 1884, there was a trace of sugar in the urine.

On February 24, 1884, the patient still under a strict diet and
the use of Clemens' solution, there was no sugar in the urine.

TREATMENT OF DIABETES MELLITUS 341

The patient went home, feehng perfectly well, and promised to
send a specimen of urine in two weeks. At no time since the be-
ginning of treatment was there any excessive quantity of urine.*

Case B. — The patient is a gentleman fifty-seven years of age,
five feet eleven and one-half inches in height, weighing one hun-
dred and seventy-two pounds. He had suffered from diabetes to his
knowledge for about one year, with thirst, fatigue after moderate
exertion and other mild symptoms. He had been under a moderate
antidiabetic diet for some weeks. After he came under my ob-
servation, his urine, under a strict antidiabetic diet, was either
entirely free from sugar or contained merely a trace, for ten months.
He had no symptoms and regarded himself as cured. For about
three months he took four drops of Clemens' solution three times
daily.

On January 17, 1884, he presented himself, passing a large
•quantity of urine of a specific gravity of 1027 and loaded with
sugar. Having regarded himself as permanently cured, he had
returned to his old diet, including sugar, and had stopped the
bromide of arsenic for six months. He felt perfectly well but had
noticed for some days that he was passing a large quantity of
urine. He was again put upon an antidiabetic diet (which I
fear was not strictly followed) with six drops of Clemens' solu-
tion twice daily. On February 7, 1884 he passed a normal
quantity of urine of a specific gravity of 1022, containing but a
trace of sugar.

In this case, I can not secure strict attention to the diet and
regular examinations of the urine. f

Case C. — This patient has been under observation since Octo-
ber, 1880. He was at that time fifty-three years of age, five feet
eight and one-half inches in height and weighed one hundred and
sixty-eight to one hundred and seventy-two pounds. Glycosuria
had been recognized a few weeks before he came under my ob-
servation; and he had been subjected to an imperfect antidiabetic
diet. He was immediately put upon a strict diet, and from Octo-
ber 21, 1880 to May 18, 1881, his urine generally contained no
sugar, although there was occasionally a trace. In this case the
diet was strictly followed, and the patient soon lost his desire for
prohibited articles, even bread.

On May 18, 1881 he was allowed the fruits in season to be
taken without sugar. On June 27 he was allowed a little bread.
His urine was practically free from sugar until February 17, 1882,
with the exception of an occasion on November 5, 1882, when it
had a specific gravity of 1029 and contained considerable sugar
following a slight excess at table in taking claret and whisky and
w^ater.

* On April 29, 1884 I received a specimen of urine from this patient. The
quantity in twenty-four hours was said to be about fifty fluidounces. The spe-
cific gravity was I022^ and contained a trace of sugar. The general health
was reported as perfect.

+ I saw this patient on April 29, 1884, and he reported himself as perfectly
well, but I did not have an opportunity of examining the urine.

342 TREATMENT OF DIABETES MELLITUS

On February 17. 1882 his urine had a specific {gravity of 1026
and contained considerable sugar. He had been living rather freely
for some time without committing any actual excesses at table.
He moderated his living and was given, in addition to the strict
diet, one-quarter of a grain of sulphide of calcium three times
daily. From February 17, 1882 to September i, 1883 his urine
was practically free from sugar when examined on ten different
occasions, once, only, presenting a mere trace. During the entire
treatment he has taken considerable exercise in walking. He took
the sulphide of calcium rather irregularly for six months, but it
was very disagreeable.

On January 11. 1883 he began to take the bromide of arsenic,
which he continued rather irregularly.

On January 23, 1884 his weight had increased to 175^ pounds.
Since September i, 1883 his diet had been practically unrestricted.
His urine had a specific gravity of 1021 and contained a small
quantity of sugar. He was put on a moderate antidiabetic diet and
the dose of bromide of arsenic was increased to five drops. On
February 7, 1884 the sugar was still marked in the urine, but he
indulged rather too freely in claret at dinner and drank some brandy
and soda during the evening. From February 7, to April 3, 1884
the urine had been nearly always free from sugar.

This may be called almost a case of cure. For the greatest
part of the time from October, 1880 to April, 1884, three and one-
half years, the urine has been practically free from sugar, for some
of the time under an ordinary diet. During this period sugar has
appeared temporarily and in small quantity, possibly as a conse-
quence of occasional indiscretions in the use of wine, which could
not by any means be regarded as excesses in a person in ordinary
health.*

Case D. — This is the case of a lady, rather stout, fifty-nine
years of age, who came to me for treatment in December, 1882.
The patient has already been referred to in connection with the
fact of the existence of sugar in urine of a low specific gravity,
(loiij) and the return of glycosuria immediately following the
suspension for one week of the administration of bromide of ar-
senic.

In December, 1880 the patient was in a deplorable condition,
suffering from some of the most distressing symptoms of diabetes.
She suffered intensely from thirst, night and day, and was forced
to pass urine nearly every hour. She also suffered greatly from
pruritus vulvae. Her disease was of five years' standing, and she
had been subjected to various forms of treatment, but never to
a strict diet. She had consulted many distinguished physicians in
this country and in Europe.

On December 16, 1882 she passed 128 ounces of urine, of a
specific gravity of 1036, containing twenty-two grains of sugar per

* On April 28, 1884 this patient reported himself as perfectly well. His
urine had a specific gravity of 1020^ and contained no sugar. The diet had
been not absolutely strict, but was what may be called moderately antidiabetic.

TREATMENT OF DIABETES MELLITUS 343

fluidounce, or 2,816 grains in the twenty-four hours. The next day
she was put upon a strict antidiabetic diet.

On December 22, 1882 the daily quantity of urine was reduced
to fifty-two ounces, with 'a specific gravity of 1026 and containing
eight grains of sugar per fluidounce, or four hundred and sixteen
grains in the twenty-four hours. The urine constantly presented
crystals of uric acid. The thirst, pruritus and constant desire to
pass urine were relieved.

With the exception of one week, this patient took Clemens'
solution, two drops three times daily, the dose finally increased to
five drops, from December 27, 1882 to April 2, 1884. The treatment
during this period consisted of the diet and Clemens' solution, with
occasional remedies to act upon the bowels. She has been almost
constantly under treatment, and I made ninety-one examinations
of the urine up to April 6, 1884. Her urine is now examined
regularly once a week.

Under treatment the quantity of sugar in the urine diminished
until the glycosuria disappeared January 2y, 1883, about thirty
days after the first examination. From January 27, 1883 to April
6, 1884, with the exception of about six weeks passed at a watering-
place in the summer of 1883, under very unfavorable conditions as
regards diet, the urine has either been free from sugar or has con-
tained a very small quantity. The quantity of urine has been nor-
mal, and the general diabetic symptoms have never reappeared.
She now uses the antidiabetic diet with the crust of one-half of
a French roll at each meal, a pint of cream daily and a little fruit
in season.

While this can not be called an instance of cure, the fact that
the patient lives comfortably and in apparently good health under
a diet that is not particularly irksome shows that cases of long
standing and presenting very unfavorable features are by no means
hopeless. This case presented in a remarkable degree the example
of a loss of desire for prohibited articles of food. She now looks
forward to eating melons in season, which is about the only decided
wish she has expressed for food not suited to her condition.*

Case E. — The patient in this case is a gentleman about fifty
years of age, living in Ohio. I examined his urine May 24, 1878
and November 17, 1881. for some reason not connected with a sus-
picion of diabetes and found no sugar. On May 4. 1882 I again
examined the urine, on account of certain diabetic symptoms, and
found a large quantity of sugar. He was at once put on the anti-
diabetic diet, which he attemnted to carry out by himself at his
home in Ohio. In January, 1884 he reported that all his symptoms
had been relieved and that he suffers nothing unless he commits
indiscretions in diet.

* The urine of this patient is examined regularly once a week, and there
has been no sugar, with the exception of a trace on one occasion, for twelve
weeks. The last examination was made on ^lay 4, 1884, and no sugar was
found. With the exception of sugar, the diet has been but little restricted for
three weeks. For the last three weeks the patient has been taking about a pint
daily of the lactic acid drink recommended by Cantani.

344 . TREATMENT OF DIABETES MELLITUS

Case F. — The patient in this case is a j^cntleman about fifty
years of age and of medium muscular and adipose development.
Having been suffering for some months from diabetic symptoms,
his urine was examined by me on March 22, 1878. I then found
a specific gravity of 1022 and a large (|uantity of sugar. He was
at once put upon a moderate antidiabetic diet.

On April 26, 1878 I found the urine normal and the diabetic
symptoms had disappeared. Between April 26, 1878 and January
ID, 1882 I examined the urine seven times, always finding it normal.
On October 14, 1882 he passed ninety-six ounces of urine in
the twenty-four hours, with a specific gravity of 1027 and contain-
ing four grains of sugar per fluidounce. His diet for some time
had been irregular, and he had depended on various remedies, such
as the bromides and the sulphide of calcium. He then began to
take the bromide of arsenic, but his diet, though moderately anti-
diabetic, was still imperfectly regulated. His urine, examined
February 20, May 18 and May 28, 1883, contained a small quantity
of sugar. On August 15, 1883 I examined the urine and found a
trace of sugar.*

This patient suffers very little from diabetic symptoms. I have
little doubt that the glycosuria could be arrested by a few weeks
of strict dietetic treatment.

Case G. — The patient is a lady, rather stout, and about seventy-
five years of age. Attention was directed to the urine on Febru-
ary 7, 1884, by excessive thirst and urination, with pruritus vulvae.
Before I examined the urine it was reported to me that she was
passing it in large quantity, the specific gravity being 1040, and
that it was loaded with sugar. Under an antidiabetic diet and the
bromide of arsenic, in three days the quantity of urine was reduced
to the normal standard and the diabetic symptoms disappeared. I
examined the urine on February 13, 19, 28, March 4, 11, 17, 21, 25,
31, and April 5, 1884. The urine, with one exception, presented
sugar in small but variable proportions ; but its quantity usually
was normal, and the specific gravity varied between 1007 and 1020.
The urine on one occasion, with a specific gravity of loio, con-
tained a trace of sugar. On March 17, the urine had a specific
gravity of 1007 and contained no sugar. The general diabetic
symptoms are now entirely relieved. The only fault in the diet is
that the patient takes a quart of milk daily. The progress of this
•case is quite favorable up to the present time.

Case H. — The patient is a large and rather corpulent man about
sixty years of age. I examined the urine December 27, 1882 and
found it with a specific gravity of 1027 and containing a consider-
able quantity of sugar. He was at once put upon an antidiabetic
diet. Under this treatment the glycosuria and other diabetic symp-
toms disappeared. In July, 1883 he was attacked with hemiplegia,

* From April 5 to May 2, 1884 I made six examinations of the urine.
The specific gravity has been between 1012^ and 1020 and a small quantity of
sugar has always been noted ; but there have been no general diabetic symp-
toms. The diet has not been rigidly carried out.

TREATMENT OF DIABETES MELLITUS 345

from which he has substantially recovered. He was reported in
March, 1884 as perfectly well, having returned to the normal diet.*

Cases I, J, K, and L. — These are cases of patients who are
constantly passing sugar in large quantities, under little or no treat-
ment, but who enjoy fair health. In one of these cases the patient
obstinately refuses to regulate the diet ; and although he suffers
but little from diabetic symptoms, he has become greatly reduced
in weight and strength wathin the past two years. A yovmg daugh-
ter of this patient, whom I saw repeatedly and who never followed
out an antidiabetic diet, died of diabetes about three years ago.
Another patient has fair health under a rather irregular diet. He
is so situated as to be unable to carry out a strict regimen. The
two other patients are large and corpulent men, who pass immense
quantities of sugar, with no restriction in diet or in drinking.

Of the fifteen cases of death the reports are generally imper-
fect. Four are reported as having died of diabetes ; one, of dia-
betic coma, possibly acetonemia; three, of albuminuria; one, of
apoplexy ; one, of hemoptysis ; one, of " inflammation of the bow-
els " ; and in the remaining four cases I have not been able to learn
■ the cause of death.

Case M. — I have already referred to this case. The patient
was a stout, heavy man about forty years of age. I examined him
November 20, 1869. He then passed 224 ounces of urine in the
twenty-four hours, with a specific gravity of 1035, containing 18
ounces and 30 grains of sugar and 624 grains of urea. He was
immediately put upon a moderate antidiabetic diet and returned
to his home in Nebraska. I heard from time to time for several
years that he enjoyed good health and had little or no glycosuria
unless he committed serious indiscretions in diet. He died of
" inflammation of the bowels," after a short illness, in August,
1881, nearly twelve years after I first saw him in 1869.

Case N. — On November 6, 1879 I saw in consultation a lady
about fifty-eight years of age, rather spare in figure, who had been
suffering for some months from diabetes. At this time the quantity
of urine was not notably increased, the specific gravity was 1030
and it contained a small quantity of sugar. The treatment had con-
sisted mainly of an imperfect antidiabetic diet. A more rigid
diet was recommended but it was not strictly enforced. On No-
A^ember 10 and 15, 1877 the urine contained a trace of sugar. On
November 29, 1877 the urine was free from sugar and the patient
was much improved. She left for her home in Cuba, and I saw
her again on September 2. 1880, when the urine was still free from
sugar. In July, 1881 she was passing large quantities of sugar,
and I learned that for several months the diet had been unre-
stricted and she had eaten sweets and fruits immoderately. She
returned to the antidiabetic diet and I found the urine free from
sugar, with all the diabetic symptoms relieved, on August 2. 1881.
She then returned to her former habits of eating and the urine was
found loaded with sugar on September 27 and October 29, 1881.

* This patient died of apoplexy, June i, 1SS4.
23

346 TREATMENT OF DIABETES MELLITUS

I learned that she died " of diabetes," never having returned to
the antidiabetic diet, in Cuba, in 1882. During the last few
weeks of her life she was much prostrated, suffering intensely
from boils and carbuncles, which were probably the immediate
cause of death.

The diet-table which follows is adapted to those who
are able to provide themselves with any kind of food re-
quired, without regard to cost, rather than to persons of
restricted pecuniary resources; but I have recoi^nized the
fact that those who are subjected to an antidiabetic diet
should secure every possible variety of food. In making
this table I have drawn largely from those already pub-
lished, particularly the list of permissible articles given by
Bouchardat; but after many trials of the so-called anti-
diabetic fiours and bread, I have come to the conclusion
as I have already stated, that they are nearly all unreliable.
I prefer to make patients abstain entirely from bread or I
allow the crust of half a French roll two or three times daily
if I can not eliminate bread altogether from the diet. The
so-called gluten breads are not only unreliable but they
soon become very distasteful. Wheii ordinary bread is al-
lowed, the physician knows, at least, about how much
starch is taken.

DIET-TABLE

Breakfast. — Oysters stewed, without milk or flour;
clams stewed, without milk or flour.

Beefsteak; beefsteak with fried onions; broiled chicken;
mutton or lamb chops, kidneys, broiled, stewed, or deviled;
tripe, pig's feet, game, ham, bacon, deviled turkey or
chicken, sausage, corned-beef hash without potato, minced
beef, turkey, chicken or game, with poached eggs.

All kinds of fish, fish-roe, fish-balls, without potato.

Eggs cooked in any way except with flour or sugar,
scrambled eggs with chipped smoked beef, picked salt cod-
fish with eggs, omelets plain or with ham, with smoked
beef, kidneys, asparagus-points, fine herbs, parsley, truffles
or mushrooms.

Radishes, cuciunbers, water-cresses, butter, pot-cheese.

Tea or coffee, with a little cream and no sugar. (Glyc-
erin may be used instead of sugar if desired.)

Light red wine for those who are in the habit of taking
wine at breakfast.

TREATMENT OF DIABETES MELLITUS 347

Lunch or Tea. — Oysters or clams, cooked in any
way except with flour or milk; chicken, lobster or any
kind of salad except potato; fish of all kinds, chops,
steak, ham, tongue, eggs, crabs or any kind of meat;
head-cheese.

Red wine, dry sherry or Bass's ale.

Dinner. — Raw oysters, raw clams.

Soups. — Consomme of beef, veal, chicken or turtle;
consomme with asparagus-points; consomme with okra;
ox-tail, turtle, terrapin; oyster or clam, without flour or
milk; chow'der, without milk or potatoes; mock turtle,
mullagatawny, tomato, gumbo filet.

Fish, etc. — All kinds of fish, lobsters, oysters, clams,
terrapin, shrimps, crawfish, hard-shell crabs, soft-shell crabs.
(Xo sauces containing flour or milk.)

Relishes. — Pickles, radishes, celery, sardines, ancho-
vies, olives.

Meats. — All kinds of meat cooked in any way except
with flour; all kinds of poultry without dressings contain-
ing bread or flour; calf's head, kidneys, sweet-breads, lamb-
fries, ham, tongue, all kinds of game; veal, fowl, sweet-
breads, etc., with currie but not thickened with flour. (No
liver.)

Vegetables. — Truffles, lettuce, romaine, chiccory, en-
dive, cucumbers, spinach, sorrel, beet-tops, cauliflower,
cabbage, Brussels-sprouts, dandelions, tomatoes, radishes,
oyster-plant, celery, onions, string-beans, water-cresses,
asparagus, artichauts, Jerusalem artichokes, parsley, mush-
rooms, all kinds of herbs.

Substitutes for Sweets. — Peaches preserved in bran-
dy without sugar; wine-jelly without sugar; '' gelee au
kirsch " without sugar; "omelette au rhum " without su-
gar; " omelette a la vanille " without sugar; " gelee au
rhum " without sugar; ** gelee au cafe " without sugar.

Miscellaneous. — Butter, cheese of all kinds, eggs
cooked in all ways except with flour or sugar, sauces with-
out sugar, milk or flour.

Almonds, hazel-nuts, walnuts, cocoanuts.

Tea or coffee with a little cream and without sugar.
(Glycerin may be used instead of sugar if desired.)

Moderately palatable ice-creams and wine jellies may be
made, sweetened with pure glycerin; but although these

348 TREATMENT OF DIABETES MELLITUS

may be quite satisfactory for a time they soon become dis-
tasteful.

Alcoholic Beverages. — Claret, burgundy, dry sher-
ry, Bass's ale or bitter beer. (No sweet wines.)

PROHIBITED

Ordinary bread, cake, etc., made with flour; sugar; des-
serts made with flour or sugar; vegetables, except those
mentioned above; sweet fruits.

ADDENDUM

This diet-table is to be found only in my little book, " Chemical
Examination of the Urine in Disease." As it may possibly be
copied and used as it appears here, I venture to add this note,
indicating the few changes I have made since 1884:

I now exclude celery from the list of salads and permit the
meat of the claws only of lobsters.

I no longer recommend glycerin alone as a substitute for
sugar, but give the following formula :

Saccharin (300 strength) 3 j I

Glycerin (C. P.) Oj.

Heat gently to complete solution.

Half a teaspoonful of this preparation, mixed with a little
cream, may be taken in a large cup of coffee ; two teaspoonfuls
will sweeten eight ounces of lemonade ; it may be used in any
other way as a substitute for sugar.

The ordinary saccharin pellets after a time become distasteful,
as they have a slightly acrid impression and soon cease to deceive
the palate. I have had patients use the mixture of saccharin and
glycerin constantly for years with entire satisfaction and with
no disturbance of digestion. (November, 1902.)

XVI

FOUR SELECTED TYPICAL CASES OF DIA-
BETES MELLITUS NOT BEFORE RE-
PORTED *

Published in the " New York Medical Journal " for November 22, 1884.

In May, 1884 I reported fifty cases of diabetes mellitus
to the " Section on Practice of Medicine and Materia Medi-
ca of the American Medical Association," and to this re-
port, which is contained in the " Journal of the American
Medical Association." July 12, 1884, I refer the Fellows of
this Association for full details of the treatment employed.
Since this publication I have had under treatment four
cases of diabetes, which are typical in many of their char-
acters, illustrating different conditions of the disease and
the effects of treatment in patients of dift'erent ages.

The first case, which, for my own convenience, I shall
designate as Case LIII, illustrates the difficulties met with
in treatment when the disease has been allowed to run its
course without restraint for a number of months.

Case LIII. — The patient was an unmarried woman, twenty-
two years of age, rather slight in figure when in health, and of
medium height. Her parents are living and in perfect health.
The family history failed to show any hereditary tendency to this
or to any other disease. When in health the patient weighed 140
pounds. This was the weight about three years before she came
under my observation. So far as I can judge from the history
of the case, the disease must have existed for two years or perhaps
longer. In January, 1884 the patient had lost about twenty pounds
in weight, had excessive urination, an abnormally great appetite
and thirst and suffered from a feeling of exhaustion after moderate
exercise. At that time she passed, as was stated, six to eight
quarts of urine in the day, which was loaded with sugar. Before
the diabetes had become developed, she had enjoyed perfect health
with the exception of dysmenorrhoea, which had existed since the

* Read before the New York State Medical Association, November 20, 1884.

349

350 FOUR CASES OF DIABETES

age of eighteen. She began to menstruate at the age of thirteen,
and at the age of eighteen fell from a wagon, striking on her feet
and sustaining no apparent injury at the time. Since this fall,
however, she had persistent dysmenorrhoea, suffering intense pain
for six or eight hours at every period. She has not menstruated
since February, 1884; and in January and February, 1884, she
suffered no pain. She was examined in October, 1884, by Dr. James
B. Hunter, who found retroversion but advised no interference
unless menstruation should return.

When the patient consulted me on August 25, 1884, she pre-
sented all the characteristic general symptoms of diabetes mellitus,
including excessive appetite and thirst, weariness after slight ex-
ercise, some pruritus vulvjc and an increased quantity of urine.
Her weight was 92 pounds. During the winter of 1883-84 and
the summer of 1884 she had indulged excessively in starchy mat-
ters and sweets, and since January had taken various remedies
without experiencing any benefit.

August 26, 1884. — The urine of the twenty-four hours measured
152 fluidounces, was pale, of a sweetish odor and had a specific
gravity of 1037. It contained 28 grains of sugar to the fluidounce,
giving a discharge of 4,256 grains (8 ounces, 416 grains) in the
twenty-four hours. There was no albumin. Microscopical exam-
ination revealed the presence of a few octahedra of oxalate of lime
with some vaginal epithelium. She was at once put upon a strict
antidiabetic diet, all starch and sugar being rigidly excluded, and
was ordered to take three drops of Clemens' solution of bromide
of arsenic three times daily.

September i. — The quantity of urine was reduced to 112 fluid-
ounces. The sugar was reduced to 12^ grains to the ounce, or
1,400 grains in the twenty-four hours. The excessive appetite
and thirst and the pruritus vulvae had disappeared. The dose of
the Clemens' solution was increased to five drops. She felt better
and stronger, and the weight, taken September 3, was increased
to 99 pounds.

September 10. — The weight had increased to 103 pounds, and
the quantity of urine was reduced to 96 fluidounces, with a specific
gravity of 1023.5. The total discharge of sugar for the day was
1,152 grains. The urine, however, presented a trace of albumin.
The treatment was continued, with the addition of two grains of
quinine three times daily. She had slight uterine pains on Septem-
ber 8, 9, and 10, this being the time in the month when her
periods occurred, but there was no menstruation. There was no
unusual thirst and the appetite was normal. She bore the strict
antidiabetic diet very well.

September 24. — The weight had slightly decreased, being re-
duced to loi pounds. The quantity of urine was 80 fluidounces,
with a specific gravity of 1025 and containing in all 800 grains
of sugar. Since September 10 she had been losing strength as
well as weight. The treatment was continued, with the addition
of one-quarter of a pint of cream and a tablespoonful of whisky
twice daily.

FOUR CASES OF DIABETES 351

October 10. — The weight was reduced to 96 pounds. The quan-
tity of urine was 80 fluidounces, with a specific gravity of 1023
and containing in all 720 grains of sugar. The patient had fol-
lowed the treatment, dietetic and medicinal, most faithfully. She had
taken, for about four weeks, griddlecakes made of Hecker's farina,
which contains only one or two per cent, of starch (?). Notwith-
standing the rigid diet, however, I had been unable to reduce the
quantity of sugar below 9 or 10 grains to the fluidounce of urine,
or 700 to 800 grains in the twenty-four hours, and the strength
and general health showed no improvement since September 24.
I decided to try to arrest the discharge of sugar by an absolute
fast of twenty-eight hours — a method recommended by Cantani.
To this plan the patient cheerfully assented. She accordingly
fasted from 8 a.m., October 10, to 12 m., October 11, remaining
in bed most of the time and taking nothing but water. The urine
passed at the close of the fast contained two grains of sugar to the
fluidounce ; but it presented oxalate of lime, a small quantity of
albumin and a few small granular casts. She bore the fast very
well, had a good appetite the next day and for several days felt
better than she had for weeks. Following the fast the former
treatment was resumed.

October 15. — The quantity of urine was somewhat reduced. Its
specific gravity was 1030 and it contained 9 grains of sugar to
the fluidounce. There was still a little albumin with a few granular
casts. The patient left for her home in Georgia on the following
■day. She was in much better general health than when I first saw
her on August 25, but I had found it impossible to arrest the dis-
charge of sugar.

My prognosis in this case is not entirely favorable. It
is probable that the excessive indulgence in sweets and in
starchy articles of food for several months dtiring the height
of the disease has rendered the glycosuria uncontrollable
beyond a certain point. Her present safety undoubtedly
lies in an antidiabetic diet, and a return to sweets and
starch would probably be promptly followed by a return of
all of the grave symptoms of the disease.*

The following case is in striking contrast to the one
just recited:

Case LV. — The patient v.'as a young girl, of medium height
and development, fifteen years of age. Her father and mother are
living and in good health and there is no hereditary tendency to
disease. A sister of the patient died at the age of nineteen, prob-
ably of diabetes mellitus. The patient began to menstruate at the

* I received a letter from the father of this patient, dated November 2,
1884, stating that " she arrived safely without detention, and bore the fatigue
of the trip astonishingly well. She is, I think, evidently stronger and better
than when she first placed herself under your treatment."

352 FOUR CASES OF DIABETES

age of thirteen and has menstruated regularly since that time.
She was in perfect health up to January, 1884, when she began
to lose flesh slightly and was " ailing " for a few weeks. She soon
improved in general health and was apparently well until the mid-
dle of August, 1884, when she was found to be passing about two
quarts of urine daily, the specific gravity of which was said to
be 1052. Since that time she has been on a moderately restricted
diet and has taken various remedies. She suffered somewhat from
thirst during August and September. Her urine was found some-
times to contain a little sugar and sometimes was free from sugar.

October 8, 1884. — I made a thorough physical examination of
the patient and found no disease. The urine was rather less in
quantity than normal, had a specific gravity of 1031 and contained
no sugar. The only abnormal condition of the urine was the pres-
ence of a large number of octahedra of oxalate of lime. The diet
had been moderately restricted. I ordered that the diet be unre-
stricted for twenty-four hours.

October 10. — After twenty-four hours of unrestricted diet, the
quantity of urine was slightly increased. It had a specific gravity
of 1036.5 and contained 31 grains of sugar to the fluidounce.
There were none of the characteristic general symptoms of dia-
betes. I ordered a strict antidiabetic diet, three drops of Clemens'
solution of bromide of arsenic three times daily, the dose to be
graduallv increased to five drops, and a pill of one-quarter of a
grain of codein and one-twelfth of a grain of podophyllin at night,
to relieve constipation should it be troublesome. The patient then
left for her home in Virginia.

October 16. — I heard from this patient and received a specimen
of urine. The treatment had been followed strictly. She had felt
perfectly well since her return to Virginia and was passing urine
in normal quantity. The urine had a specific gravity of 1015 and
contained no su""Hr.

In this case the glycosuria seemed to be easily control-
lable. After examining the urine I wrote to the friends
as follows:

" I suggest that the dietetic and other measures of treatment
be strictly followed until the middle of December. If. at the end
of that time, the urine should continue free from sugar, the patient
may begin to eat a little bread and gradually return to the usual
diet, except that she should never eat sugar or sweets. The urine
should be examined from time to time while she is in process of
returning to the normal diet."

My prognosis in this case is favorable. With proper
attention to the diet I should expect a cure; but it will be
necessary to examine the urine occasionally for a long time
in order to detect, at the earliest moment, any tendency to-
a return of the glycosuria.

FOUR CASES OF DIABETES 353

Case LI. — This patient was a robust man, unmarried, thirty-
four years of age, 5 feet 7 inches in height and weighed 177
pounds. He had always eaten largely of bread and sweets. For
several weeks he had a moderate increase in thirst and had not
been " feeling very well." His urine had been examined and it
was said to contain sugar. His previous health had been good.
He had occasionally committed sexual excesses.

I examined this patient on April 8, 1884 and found no disease.
The urine was somewhat less in quantity than normal, with a spe-
cific gravity of 1035 and was turbid with urates. It contained no
sugar. During the day on which this urine was passed the patient
had abstained from bread and sweets.

April 10, 1884. — I examined a specimen of the urine passed dur-
ing the day, the diet having been unrestricted. It had a specific
gravity of 1026 and contained a small quantity of sugar.

June 2. — Since April 10 the patient had followed a strict anti-
diabetic diet and had taken three drops of Clemens' solution of
bromide of arsenic three times daily. His urine had a specific grav-
ity of 1030, was normal in quantity and contained no sugar. The
patient felt perfectly well, but his weight had been reduced to 167
pounds. The dose of Clemens' solution was increased to five
drops.

July 16. — The patient was still perfectly well, the diet was not
irksome and the urine was normal, free from sugar and had a
specific gravity of 1024. The weight had been reduced to 161
pounds. The treatment was continued.

August I. — The patient continued well, but the weight was re-
duced to 159 pounds. The urine was normal, free from sugar and
had a specific gravity of 1029. The treatment was continued.

August 14. — The patient continued well and the weight had
increased to 161 pounds. The urine contained no sugar and had
a specific gravity of 1026.

August 20. — The patient continued in the same condition. The
weight was 157 pounds and he looked and felt in perfect health.
The urine contained no sugar and had a specific gravity of 1031.
The patient then passed from under my observation. The Clemens'
solution was stopped and he was instructed to gradually return to
a normal diet, but never to eat sugar or sweets and to carefully
abstain from excesses of any kind.

In this case the glycosuria was readily controllable and
an apparent cure was effected.

The fourth case is that of a man, fifty-nine years of age,
in whom the disease, although of at least a year's standing,
yielded promptly to treatment.

Case LII. — The patient, a married man, fifty-nine years of age,
was 5 feet 8j inches in height and weighed 227 pounds. He was
robust, had always enjoyed good health and had been rather a free
liver, but without excesses of any kind. The family history gave
no evidence of hereditary tendency to disease. For the nine months

354 FOUR CASES OF DIABETES

previous to the time when he came under my observation he had
suffered from excessive urination, annoying thirst, abnormal weari-
ness and impairment of appetite. During this period he had lost
about twenty pounds in weight.

August II, 1884. — I examined a specimen of the urine. Its
quantity in twenty-four hours had not been measured but was
undoubtedly excessive. It had a specific gravity of 1023 and con-
tained considerable sugar with abundant uric acid crystals. He
was at once put upon a rigid antidiabetic diet, with three drops
of Clemens' solution of bromide of arsenic three times daily.

August 19. — The general diabetic symptoms had entirely disap-
peared. The urine was normal, with a specific gravity of 1020
and free from sugar. The weight was unchanged at 227 pounds.

August 26. — The patient felt perfectly well. The urine had a
specific gravity of 1012.5 and was free from sugar. The dose of
Clemens' solution was increased to five drops.

September 28. — The patient continued to feel perfectly well.
The urine had a specific gravity of 1030 and was free from sugar.
The weight had increased to 235 pounds. The Clemens' solution
was stopped and the patient was allowed to eat a little bread.

October 11. — The patient felt that he was entirely cured. His
weight was 233 pounds. The urine was perfectly normal, had a
specific gravity of 1020 and was free from sugar. He was directed
to follow a reasonable diet, not abstaining entirely from starchy
matters, but avoiding sugar and sweets. He was directed to have
his urine examined again in about six weeks.

The limited time at my disposal prevents me from giv-
ing the diet-table for diabetics and other details of treat-
ment, which would be merely a repetition of what is con-
tained in my paper on the '' Treatment of Diabetes Mel-
litus," published in the " Journal of the American Medical
Association," July 12, 1884, and in the sixth edition of my
little book on the " Chemical Examination of the Urine in
Disease." The diet-table is very varied and is not difificult
to follow, the greatest hardship to patients being depriva-
tion of bread. It is a curious fact, however, that after fol-
lowing a strict diet for two or three weeks, diabetics lose
their craving for many prohibited articles of food, and the
diet becomes by no means irksome. The patients, in all
of the cases here reported, were in good circumstances and
both willing and able to follow strictly the prescribed diet.

In presenting an account of these four typical cases to
the Association, I have purposely put the unfavorable case
first. This is the second case that I have met with in which,
patients being willing to submit absolutely to treatment,
I have not been able to arrest the glycosuria. In this case,

FOUR CASES OF DIABETES 355

for many months the patient indulged inordinately in
sweets; and the disease, which was complicated with albu-
minuria, had become so thoroughly confirmed that al-
though the general symptoms were controlled, even total
abstinence from food did not remove the sugar from the
urine after the first week of treatment.

XVII

LITHIUM CARBONATE AND SODIUM AR-
SENATE DISSOLVED IN CARBONIC ACID
WATER IN THE TREATMENT OF DIABETES
MELLITUS

Published in " The Medical News " for July 9, 1887.

At a recent meeting of the Therapeutical Society of
Paris, Dr. Martineau made a brief communication in which
he stated that for several years he had treated cases of dia-
betes mellitus with a solution of lithium carbonate and
sodium arsenate in ordinary carbonic acid water, to the ex-
clusion of every other medicinal remedy and with a moder-
ately strict antidiabetic diet. Dr. Martineau claimed that
he had cured sixty-seven out of seventy cases of arthritic
diabetes by this method of treatment, which he had bor-
rowed from a practitioner now dead, the late Prof. Rouget^
of Paris. The communication was discussed by Dr. Du-
jardin-Beaumetz and others, who regarded the method as
so simple and. to say the least, innocuous, that it was worthy
of trial.

The preparation recommended by Dr. Martineau was
the following.* Into an apparatus such as is commonly
used in Paris for making carbonic acid water, are put twenty
centigrammes of lithium carbonate and a tablespoonful of
a solution of twenty centigrammes of sodium arsenate in
five hundred grammes of distilled water. The quantity of

* " Bulletin et memoires de la societe de therapeutique," Paris, 30 mars,
1887, i8e annee, No. 6, p. 41.

Reduced to the English standard the formula would be about as follows :

Lithium carbonate 3 grains.

Sodium arsenate iVi grain.

Carbonic acid water 2 pints.

This formula has been published in a number of medical journals. In some it
is stated that a teaspoonful of the solution of sodium arsenate is used instead of a
tablespoonful. This error arises from a faulty translation of " cuilleree a bouche,"
which means a tablespoonful. The term for a teaspoonful is " cuilleree k cafe.'*

356

MEDICINAL TREATMENT OF DIABETES 357

carbonic acid water used is about one litre. This quantity
is to be drunk by the patient during each day, either by
itself or mixed with ordinary wine at meals.

The simplicity of the proposed remedy led me to make
an efifort to test its efificacy in certain obstinate cases under
treatment for diabetes. I endeavored first to have the
agents introduced into the ordinary siphons of soda water
prepared and sold in New^ York; but the manufacturers
were unwilling to do this and I was forced to adopt some
other method of preparation. It was finally suggested to
me to put up the preparation in ordinary beer bottles with
patent stoppers which could be replaced after using a cer-
tain quantity. This was done, two of these bottles making
the equivalent of the quantity administered daily by Dr.
Martineau.

I was not prepared to make a trial of the remedy before
the middle of April and have used it since then in but
three cases — a time too short, and a number of cases too
small to admit of anything like definite conclusions. How-
ever, in the hope of inducing others to make similar trials. I
venture to present the imperfect results of my own brief
experience.*

Case LXXXV. — x\n unmarried lady, fifty years of age, weigh-
ing 115 pounds. Her weight in health was 140 pounds. The
disease was recognized six months before she came under my
care.

March 11, 1886. — The general diabetic symptoms were marked,
and the virine contained 2i grains of sugar per ounce. The patient
was put on an antidiabetic diet, according to my published diet-
table,f with Clemens' solution of bromide of arsenic, five drops
three times daily. March 19 the quantity of sugar was 7 grains
per ounce; March 26, 14 grains; April 2 there was no sugar; and
April 7 no sugar. From March 26 to April 7 the diet was abso-
lutely antidiabetic, no bread being taken.

June 17. — The urine had been free from sugar since April 2
under the antidiabetic diet. The quantity was normal and the
body-weight had increased by four pounds. The patient expressed
herself as feeling " nearly well."

July 28. — The diet for several weeks had been very imperfect,
the diabetic symptoms had returned, and the urine contained 24

* The numbers of these cases are made to correspond with the numbers in
my book of records.

+ " Jorunal of the American Medical Association," July 12, 1SS4, and
" Manual of Chemical Examination of the Urine in Disease," sixth edition.
New York, 1884, p. 85. See also p. 346 of this volume.

358 MEDICINAL TREATMENT OF DIABETES

grains of sugar per ounce. From this date until April 15, 1887^
sugar was found in the urine at every examination, the quantity
apparently varying with the diet. During this time I made ten
examinations. The general diabetic symptoms were much dimin-
ished in prominence although they were distinct. The body-weight
did not undergo much change.

April 15, 1887. — The daily quantity of urine was 45 ounces
containing 20i grains of sugar per ounce.

April 16. — With no change in general treatment, the patient
was put on the solution of lithia and arsenic, about two pints
daily.

April 26. — The quantity of urine was 37 ounces containing 8
grains of sugar per ounce.

May 4. — The diet had been relaxed. The quantity of urine was
52 ounces containing 18 grains of sugar per ounce.

May 12. — The diet had been more rigid. The quantity of urine
was 32 ounces containing 6 grains of sugar per ounce.

May 29. — The diet had been imperfect. The quantity of urine
was about 40 ounces containing 244 grains of sugar per ounce.

On May 12 there was some swelling of the eyelids and the
quantity of the solution of lithia and arsenic was reduced one-half.
On May 14, 15 and 16 the lithia and arsenic were omitted.

The patient was weak and depressed when the treatment with
lithia and arsenic was begun. On May 23, about five weeks after,
she felt much better and stronger, with a gain of two or three
pounds in weight.

With the exception of the indefinite statement by the patient
that she felt better in spirits and stronger, the lithia and arsenic
seemed to have produced no marked effects. This patient is pecul-
iarly susceptible to starchy and saccharine articles of food. Under
measures of treatment that had been very beneficial in other cases,
she has lately shown little or no improvement ; and the most favor-
able view to take of the case is that the disease, under proper die-
tetic treatment, may not progress rapidly.

Case XCIII. — A gentleman, sixty-one years of age, 5 feet 5J
inches tall, weighing 157 pounds. The disease was recognized
fourteen years ago.

November 19, 1886, the patient came under my care. The
quantity of urine was 90 ounces containing 19 grains of sugar
per ounce. The diet had been very imperfect, milk and grapes
having been taken freely. He was put upon a strict antidiabetic
diet, with Clemens' solution, five drops three times daily, and one
and a half ounces of whisky three times daily. I saw the patient
but once and heard of the progress of the case from time to time
from his physician in the country.

April 6, 1887. — The patient had not been doing well. He had
lost thirteen pounds in weight ; the appetite had become very poor
and there was great suffering from pains about the chest and in
the limbs.

April 20. — The general condition was about the same but the
quantity of urine was normal with 6j grains of sugar per ounce.

MEDICINAL TREATMENT OF DIABETES 359

The patient was then put upon the solution of lithia and arsenic,
two pints daily.

May II. — The general condition was about the same but the
quantity of urine was reduced to 40 ounces and it contained no
sugar.

May 19. — It was reported to me that the general condition of
the patient was better and that he was stronger. No report was
made of the condition of the urine.

Case XCV. — A married lady, sixty-three years of age, of me-
dium height, weighing 155 pounds. At the present time she has
been under my care for a little more than three months. The dis-
ease was recognized twelve years ago. In health the patient
weighed about 200 pounds.

February 9, 1887. — The general diabetic symptoms are well
marked. The quantity of urine is excessive and it contains 23
grains of sugar per ounce. The patient was put upon the anti-
diabetic diet, with Clemens' solution, iive drops three times daily.

February 14. — The quantity of urine was normal and it had so
continued up to this date. The quantity of sugar was 13 grains
per ounce. The diabetic symptoms had disappeared.

April 4. — The urine has been examined regularly once a week
and the quantity of sugar has been gradually reduced to one grain
per ounce. The appetite became very poor about a week ago, and
insomnia was very troublesome, with shooting pains over the liver.

April 17. — The patient was put upon the solution of lithia and
arsenic, two pints daily.

April 25. — The quantity of urine was about normal and it
contained no sugar.

May 17. — The general condition has improved. Since April
25 the urine has contained about one grain of sugar per ounce.
Within the past eight months the patient has lost fourteen pounds
in weight.

May 24. — The general condition of the patient is much im-
proved. The quantity of urine is normal and it contains about
one grain of sugar per ounce.

The general result of the observations on the three cases
reported is quite indefinite. The effects of the solution
of lithia and arsenic were not well marked, and the slight
improvement under its use in Cases XCIII. and XCV.
might have beeii due to other causes. I shall, however,
contintie the remedy in these three cases and employ it in
other cases until I shall have given it a fair trial; btit I do
not feel that it would be prudent in any case to relax the
dietetic treatment.

With other so-called specifics for diabetes mellitus I
have had some experience.

I have given calcium chloride in a number of cases, with
entirely negative results.

36o MEDICINAL TREATMENT OF DIABETES

In several cases I have used jaml)ol, also with negative
results.

1 have never given opium, except for the relief of pain
and insomnia; but in cases in which it has been used it has
been well tolerated.

I nearly always prescribe at first Clemens' solution of
bromide of arsenic. This remedy does no harm, and in
many cases it seems to exert some control over the thirst,
polyuria and the quantity of sugar in the urine.

I invariably interdict the use of milk and skim milk.
In a number of cases in which it has been taken by patients
on their own responsibility, I have observed that it prompt-
ly induced thirst, polyuria and an immense increase in the
discharge of sugar. In some instances in which my pub-
lished diet-table has been copied, milk has been added.
This addition, it seems to me, is most unwarrantal)le; and
the use of milk more than counteracts the beneficial results
to be expected from the antidiabetic diet properly carried
out.

For the past three years I have recommended a gluten
bread which at first contained between two and five per
cent, of starch. Within a year, however, it has seemed to
act unfavorably. I have lately had a number of analyses
made of this bread, and it has been found to contain about
thirty per cent, of starch. Within the last two months I
have abandoned its use, although this has greatly in-
creased the difficulties of dietetic treatment.

I have not been able to study the details of the seventy
cases mentioned by Dr. Martineau, sixty-seven of which
he reported as cured.*

The experience of all who have followed out any con-
siderable number of cases of diabetes teaches that the gly-
cosuria nearly always returns under a careless diet ; and my
ow'n experience is no exception to this general rule. That
such an exception should have occurred in the experience
of Dr. Martineau would, indeed, be remarkable.

Including the three cases already briefly reported, I
have now under observation and treatment ten cases which
I have follow-ed for variable periods. It may be interesting

* A brief account of three cases, treated by Dr. Martineau, is given in the
*' Therapeutic Gazette," Philadelphia, May i6, 1887, p. 330.

MEDICINAL TREATMENT OF DIABETES 361

to compare seven of these cases with the three treated witli
the solution of Hthia and arsenic.

Case LXXXIII. — A gentleman, fifty-eight years of age, 5 feet
7 inches tall, weighing 156 pounds. I began the treatment of this
case January 17, 1886. The disease had been recognized four years
before. The patient had been under the care of an eminent English
physician, who gave the opinion, after two or three years of treat-
ment, that the disease would never be entirely cured.

January 17, 1886. — The diabetic symptoms were distinct but
slight. The patient had been under a moderately strict antidiabetic
diet. The quantity of urine was 60 ounces containing 2h grains of
sugar per ounce. The patient was put upon an absolute antidia-
betic diet, without any bread, for two days, and Clemens' solution,
three drops three times daily, the dose to be increased in five days
to five drops. Two days after, the urine was free from sugar. The
patient has continued to be perfectly well in every way up to the
present time, being very actively engaged in business.

From January 17, 1886 to May 22, 1887 the urine has been
examined twenty-seven times. On December 19, 1886 a trace of
sugar was found, this being the only examination in which the
urine was not free from sugar. The diet was strict, antidiabetic
bread being used for the first three months. Since then, while the
patient has been careful, the diet has been rather liberal and the
patient has not suffered any serious privation.

Case LXV. — A gentleman, forty-one years of age, 6 feet tall,
weighing 205 pounds. The disease had been recognized six months
and the patient had lost about forty pounds in weight.

April 22, 1885. — The patient had the usual diabetic symptoms
in a marked degree. The quantity of urine was excessive and it
contained 21 grains of sugar per ounce. The patient was subjected
to essentially the same course of treatment as detailed in Case
LXXXIII. In four days the urine was found free from sugar
and the diabetic symptoms had disappeared. Between April 22
and December 22, 1885 ^he virine was examined thirty-one times.
August ID, the urine contained 9 grains of sugar per ounce; Sep-
tember I, no sugar; December 10, 3i grains of sugar per ounce;
December 22, no sugar. On the two occasions when sugar was
found, its presence was probably due to indiscretions of diet, and
it promptly disappeared under a strict regimen. After the first
two months of treatment the diet was but little restricted. Since
December 22 I have seen the patient casually from time to time
and he has reported himself as perfectly well.

Case XCI. — A gentleman, fifty-six years of age, 5 feet 8
inches tall, weighing 166 pounds. Twelve years ago he weighed
200 pounds. Sugar was recognized in the urine eight years before
the patient came under my care.

October 14, 1886. — The general diabetic symptoms are slight.
For the past eight years the patient has been under a very imper-
fect antidiabetic diet, and so far as I can learn, the presence of
sugar in the urine has been constant. The urine is now normal in
24

362 MEDICINAL TREATMENT OF DIABETES

quantity and contains 25^ grains of sugar per ounce. The patient
was put upon essentially the same course of treatment as in Cases
LXXXIII. and LXV. On October 21 the urine contained 13^
grains of sugar per ounce ; on October 26, 1 1 grains per ounce.

October 29. — The patient was subjected to an absolute fast of
thirty-six hours, after the method proposed by Cantani,* taking
during that time nothing but water. The fast was borne very
well, and on the day following the patient expressed himself as.
" feeling as well as he had felt in ten years." The quantity of
urine during the last twenty-four hours of the fast was 25 ounces
and it contained no sugar. The ordinary antidiabetic diet was
then resumed. October 31, the urine contained 13 grains of sugar
per ounce; November 3, 10 grains. From November 9 to 20, there
was no sugar. On February 2^, 1887 I heard from the patient.
His urine had been repeatedly examined and no sugar had
been found. He reported that his " general health had been
very good."

Case VI. — A gentleman, about sixty years of age, 5 feet 6
inches tall, weighing 185 pounds. From March 22, 1878 to Febru-
ary 24, 1885 I had repeatedly examined the urine of this patient
while he was partly under the care of the late Dr. Austin Flint.
From April 21, 1878 to January 10, 1882 the urine was free from
sugar. From October 14, 1882 to February 24, 1885 the urine had
generally contained sugar, sometimes in large quantity.

December 13, 1886. — The patient came under my direct care.
The quantity of urine was about normal and it contained 18 grains
of sugar per ounce. The patient was languid and easily wearied
but had no abnormal thirst. He was put upon the usual treatment
and took no bread. On December 19 he was much improved. The
urine contained 7^ grains of sugar per ounce. The variations in
sugar for a few weeks were as follows : December 23, 6 grains per
ounce; December 26, 3 J grains; January i, 1887, a trace of sugar;
January 8, a trace of sugar.

May 24, 1887. — The patient had been absent from the city from
January 12 to May 4. He now feels perfectly well. On May 4 and
24 the urine contained a faint trace of sugar. Since December 13,
1886 the patient has taken no bread. The antidiabetic diet has
been rigidly carried out and the appetite has been tempted by skil-
fully prepared dishes within the limits of the " diet-table," so that
the want of bread has not been a serious privation.t

* Cantani, " Le diabete sucre," p. 402. Paris, 1876.

+ In many regards this case is of great interest. Its progress from March
22, 187S to August 15, 1883 was reported in my article in the "Journal of the
American Medical Association " for July 12, 1S84, Case F. On April 18, 1871,
while the patient was under the care of Dr. Brown-Sequard for some slight
nervous disorder, I examined the urine and found it normal. I recognized
sugar in the urine, March 22, 1878. Under a moderately strict diet the sugar
promptly disappeared and was not discovered again until October 14, 1882,
three years and nearly seven months after, although the diet was unrestricted
during the greatest part of this time. This might have been regarded as a case
of transient glycosuria if diabetes had not become confirmed in 1882 and 1883,

MEDICINAL TREATMENT OF DIABETES 363

Case XCII. — A gentleman, fifty-one years of age, 5 feet 11
inches tall, weighing 208 pounds. Five months before he came un-
der my care he was examined for life insurance and no sugar was
found in the urine. About three months later there were thirst,
polyuria, weariness, etc., and sugar was found in the urine.

October 20, 1886. — The quantity of urine was 100 ounces con-
taining 31 grains of sugar per ounce. The general diabetic symp-
toms were marked. The patient was put upon the antidiabetic diet
and Clemens' solution. On October 2"] the quantity of urine was
reduced to 40 ounces and it contained no sugar. The diabetic
symptoms had entirely disappeared. November 4 and 27 the con-
ditions were the same. The patient then removed to the West.
On January 28, 1887 he wrote me that he was perfectly well. On
April 28 he wrote that he was as " good as new." Since his re-
moval to the West the urine has been repeatedly examined and no
sugar has been found. The treatment has been continued, with
slight relaxation in the diet.

Case LXXVII. — A gentleman, twenty-four years of age, 5 feet
5i inches tall, weighing 132 pounds.

October 28, 1885. — The general diabetic symptoms were
marked. The patient had lost twelve pounds in weight within the
past three weeks. The quantity of urine was 112 ounces containing
28 grains of sugar per ounce. The patient was put upon the treat-
ment already described. On January 6, 1886 the diabetic symptoms
had disappeared and the quantity of urine was reduced to 50 ounces
containing 4 grains of sugar per ounce. On May 19 and June 30
the urine contained no sugar. On September 8 the quantity of
urine was 90 ounces containing iii grains of sugar per ounce.
The diet had been imperfect for about two months.

March 2, 1887. — The urine was normal in quantity and it con-
tained 9 grains of sugar per ounce. The patient had been eating
freely of antidiabetic bread, which, as I have stated, probably
contained about thirty per cent, of starch.

Case LVIII. — A gentleman, forty-three years of age, 5 feet 9
inches tall, weighing 204 pounds. The disease is probably of eight
or ten years' standing, but sugar was recognized in the urine only
one year before the patient came under my care.

November 30, 1884. — The diabetic symptoms were marked.
The urine was very abundant and contained 6 grains of sugar per
ounce. The patient was put upon the treatment already described.
On December 13 the s\mptoms had disappeared, the urine was re-
duced to the normal daily quantity and there was no sugar.

July 7, 1885. — The patient had been perfectly well. The urine
had been examined seven times since December 13, 1884 and no
sugar was found. The diet had been well carried out.

September 20. 1886. — The quantity of urine was 55 ounces.
The morning urine contained 15^ grains of sugar per ounce and
the evening urine, 30 grains. The diabetic symptoms had returned
in a moderate degree.

October 12. — The urine was normal in quantity and contained
14^ grains of sugar per ounce. The antidiabetic treatment was

364 MEDICINAL TREATMENT OF DIABETES

resumed. The diet had been unrestricted since October, 1885, the
patient then regarding himself as cured.

October 16. — The urine was normal in quantity and contained
9^ grains of sugar per ounce.

November 16. — The urine contained no sugar and the diabetic
symptoms had disappeared. On January 24, 1887 the conditions
were the same.

April 13, 1887. — The urine contained li grain of sugar per
ounce. The patient had been travelling and the conditions for
maintaining an antidiabetic diet were unfavorable. The patient
had been eating freely of antidiabetic bread.

The ten cases reported are all that are now under my
immediate observation. At the risk of being tedious, I
have given certain details reganHng these cases, although
my records have been considerably abridged in this article.
These cases seem to me to be quite instructive. Taken in
connection with my other recorded cases, they lead me
to the following conclusions:

I. In the three severe cases in which I have used the
solution of lithium carbonate and sodium arsenate in car-
bonic acid water, no marked effects have been observed in
the few weeks during which the remedy has been em-
ployed; but the treatment seems to me to be worthy of
more extended trial and it may be useful in mitigating the
severity of a strict antidiabetic diet.

II. The so-called specifics for diabetes have little if any
efifect. An exception, however, may be made in favor of
the bromide of arsenic, which has sometimes seemed to me
to control to a slight extent the thirst, polyuria and dis-
charge of sugar.

III. The main reliance in treatment is to be placed
upon an antidiabetic diet. This has fallen somewhat into
disrepute because it is seldom efficiently carried out. In
no single instance, out of ninety-nine recorded cases, have
I found that the antidiabetic diet had been enforced.

IV. Milk should be absolutely interdicted. Its influ-
ence over the progress of the disease is prompt, powerful
and most injurious.

V. There are certain cases in which dietetic treatment
promptly arrests the glycosuria and keeps it under con-
trol. There are other cases in which treatment seems to
be of little avail, except, possibly, in retarding the prog-
ress toward a fatal result. Of the ten cases reported and

MEDICINAL TREATMENT OF DIABETES 365

now under observation, seven are amenable to treatment
and three are obstinate.

VI. A confirmed diabetic may be cured, in the sense
that all symptoms will disappear; but the disease is likely
to return at any time under an unrestricted diet. Still,
moderate care in diet will sometimes secure immunity.

VII. A patient who has once had diabetes should have
his urine examined every few weeks. Glycosuria always
precedes the general symptoms of the disease, and these
general symptoms may sometimes be forestalled by proper
treatment employed so soon as sugar makes its appear-
ance in the urine.

VIII. As the disease returns, either from imprudences
in diet or from other causes, the successive recurrences
present greater and greater difficulties in the way of treat-
ment.

XVIII

THE INFLUENCE OF EXCESSIVE AND PRO-
LONGED MUSCULAR EXERCISE ON THE
ELIMINATION OF EFFETE MATTERS BY
THE KIDNEYS

Published in the " New York Medical Journal " for October, 1870.

In the month of May, 1870, Weston, the pedestrian,
attempted to walk one hundred miles in twenty-two con-
secutive hours. This feat was to be accomplished in an
enclosure known as the Empire Skating Rink; a square
building, well ventilated, in which a rectangular track was
laid out, measuring nearly one-eighth of a mile. The
weather was mild and clear, a pleasant day for that season
of the year. This feat of endurance was accomplished in
twenty-one hours and thirty-nine minutes. Attracted by
the interest felt in this effort, I was present during the last
three hours of the walk. It is not pertinent to the scientific
questions involved to discuss the objections raised in regard
to the exact measurement of the course, the style of walk-
ing, etc.; suffice it to say that, practically, Weston made
one hundred miles, a few feet more or less perhaps, in twen-
ty-two consecutive hours — a fact which none interested
upon one side or the other have denied. While at the rink,
I ascertained from the superintendent and judges that all
of the urine passed during the walk had been collected, as
a mere matter of convenience, in a single vessel. This urine
I obtained entire and subjected it to analysis.

It is evident to any physiologist that there is much
scientific interest attached to the quantitative analysis of
the urine passed during such an expenditure of muscular
and nerv'ous force as is involved in walking one hundre'd
miles in twenty-two hours: particularly in view of the recent
observations of Fick and Wislicenus, Frankland, Haughton
366

PROLONGED MUSCULAR EXERCISE 367

and others, which seem to show that muscular exertion,
under certain conditions of diet, does not increase the
elimination of urea. This effort is nearly the maximum
of what a person endowed with unusual powers of endur-
ance is capable; and I embraced the opportunity of as-
certaining what effect such an amount of muscular exercise
would have upon disassimilation. To give full value to
my observations, it became necessary to compare the
elimination of effete matter during the walk with the daily
excretion under ordinary conditions. In all points con-
nected with these investigations, I have had the coopera-
tion of Weston; but his absence from the city prevented
my procuring a specimen of the ordinary urine until
August. The specimen then obtained, however, seemed
to me to answer perfectly for purposes of comparison.

Prefacing my observations with the statement that the
idea of entering upon them originated during the last two
hours of the walk, so that the comparison of the urine
under exercise with the ordinary urine was necessarily
made with a specimen collected some time after, I shall
proceed to detail the facts observed and to make from
them such physiological deductions as seem to be admis-
sible. All the statements in regard to the condition, diet,
etc., have been submitted to Weston and been carefully
corrected.

Weston is thirty-one years of age, of medium height
and rather lightly built, weighing, in ordinary clothing,
about one hundred and thirty pounds. Allowing eight
pounds for clothing, his ordinary weight would be about
one hundred and twenty-two pounds. As would be ex-
pected of a person of such endurance his general health is
perfect. His habits, as regards eating and sleeping, are
very irregular. He is likely to be at work all night, sleep-
ing part of the day, and his meals may be taken at any
hour. He has never been through a regular system of
training as a preparation for any of his pedestrian feats, but
simply takes moderate exercise by walking. The follow-
ing was his condition at the time of the walk:

The weight was one hundred and seventeen pounds,
naked, allowing eight pounds for clothing. This is five
pounds less than his ordinary weight. His physical con-
dition was perfect. The lower limbs were well developed

368 PROT,ONGRD MUSCULAR EXERCISE

and " fine," with the chest and upper extremities very
lii^ht.

At 12.15 ^- M., the walk was begun and the hundred
miles were accomplished in twenty-one hours and thirty-
nine minutes, ending at 9.45 p. m. At the end of the walk
Weston did not seem fatigued, but appeared brisk and
bright and was as well as ever on the following day. No
urine was passed up to 10.15 P- m.; so that the urine col-
lected was practically the urine of twenty-two hours.

During the walk Weston took the following articles of
food in small quantities and at short intervals:

Between one and two bottles of beef-essence; two bot-
tles of oatmeal-gruel; sixteen to eighteen eggs, raw, in
water. He drank a little lemonade and took water very
frequently, a mouthful at a time, only to rinse his mouth.
While walking the last ten miles he took two or three swal-
lows of champagne and about two and a half fluidounces of
brandy in ten-drop doses. The head and face were sponged
freely at short intervals and the food and drink w^ere taken
mainly on the walk.

All the urine that was passed during the walk w-as
received into a pail in a little muslin enclosure by the side
of the track. There was no discharge from the bowels dur-
ing that time. I have taken the quantity as representing
twenty-two hours, and have calculated from that the
quantity to represent twenty-four hours.

Air the analyses were made by the processes described
in my little work on " Chemical Examination of the Urine. '^
The urea was estimated by Davy's method w-ith hypo-
chlorite of soda, the French Labarraque's solution, a so-
lution which had been carefully corrected and compared
W'ith Liebig's method. The chlorine w-as estimated by a
graduated solution of nitrate of silver; the sulphuric acid,
by a graduated solution of chloride of barium; and the
phosphoric acid, by a graduated solution of sesquichloride
of iron. The uric acid was estimated by actual weight,
evaporating the urine to a thick syrup, extracting the urea,
creatin, creatinin and coloring matter wath absolute alco-
hol, setting free the uric acid and extracting the inorganic
salts with very dilute hydrochloric acid, and collecting the
uric acid on a filter. The processes in the analyses of both
specimens of urine w^ere identical. The examination was

PROLONGED MUSCULAR EXERCISE

569

begun about fourteen hours after the last urine had been
passed. The examination of the specimen taken for com-
parison was begun sixteen hours after it had been col-
lected.

EXAMINATION OF URINE PASSED DURING THE WALK

Weight of body, without clothing, one hundred and
seventeen pounds.

Articles of food and drink taken: Beef-essence, between
one and two bottles; oatmeal-gruel, two bottles; sixteen to
eighteen eggs, raw, in water; lemonade, about half a pint;
champagne, about three fluidounces; brandy, two and a half
fluidounces; water to rinse the mouth every few minutes,
and but little swallowed.

No sleep during the twenty-two hours.

Table I. — composition of the urine

Quantity in the twenty-two hours, 73^ fluidounces (esti-
mated for twenty-four hours, 80 fluidounces); acidity
normal; color rather light canary; odor strongly urinous
but normal; specific gravity, 1011.55; no abnormal mat-
ters; microscopical examination negative.

Perfluidounce,

Urea

Chlorin

Sulphuric acid. .
Phosphoric acid (total) j i . 504
Phosphoric acid (with

alkalis) * 1.2S0

Phosphoric acid (with

earths)* 0.224

Uric acid I0.500

5.779 grains,
1. 120 "
0.920 "

In 22 hours.

424.756 grains.

82.320 '*

67.620 "

110.544 "

94.060 "

16.484 "

36.750 "

Per hour.

In 24 hours.

19.307 grains.

3-742 "

3-074 "

5.025 "

4.275 "

0.750 "

1.670 "

463. 36S grains.

89.808

73.776 "

120.600 "

102.600 "

18.000 "

40.080 "

On August 20, 1870 Weston began to collect for me
the urine of the twenty-four hours, from 6 P. m., the 20th,
to 6 p. M., the 2 1 St. The weather was warm but not oppres-
sive. His habits of life were about the same as before his
walk of May 25. He wrote the greater part of the night of
the 19th and slept from 4.30 a. m. to 8.15 a. m. of the 20th.

* Approximative.

370 PROLONGED MUSCULAR EXERCISE

He then went up the Hudson River, and on the steamboat
took a light breakfast at 1 1 a. m., consisting of rare beef-
steak, fried potatoes and cokl bread with water. Between
that time and 3 p. m. he walked two miles. At 3 p. m. he
took dinner as follows: Broiled ham with eggs, stewed to-
matoes, fried potatoes and sweet corn, drinking one glass
of fresh milk and two glasses of claret wine with water.
At 5.45 he ate of muskmelon and a few pears.

He began to collect the urine at 6 p. m. At 7 p. m. he
ate a supper of pickled lambs' tongues with warm, light
biscuit and drank one cup of tea. He slept from midnight
till 7 A. M., then rose for a moment, retiring again and
sleeping until 12 m. of the 21st. At 2 p. m. he ate a hearty
breakfast (or diimer) of cold corned beef, hot bread-cakes
and one slice of bread and drank one cup of coffee. He did
not eat again until after 6 p. m., the limit of the time for
collecting the urine.

During the afternoon of the 21st he drank one glass of
Ottawa beer (a mild, effervescing root-beer) and smoked
two cigars.

At II p. M. August 20 he had an evacuation of the
bowels but did not lose anv urine.

EXAMINATION OF THE URINE OF TWENTY-FOUR HOURS
UNDER ORDINARY CONDITIONS.

Weight of body without clothing, one hundred and
twenty-two pounds.

Articles of food and drink taken: Supper — Pickled
lambs' tongues, warm, light biscuit, one cup of tea. Din-
ner— Cold corned beef, hot bread-cakes, one slice of bread,
one cup of coffee. One glass of Ottawa beer and two cigars
during the day.

Slept between eleven and twelve hours. Ate salt ham
the day before at 3 p. m.

Table H. — composition of the urine

Quantity in twenty-four hours, 33 fluidounces; acidity
rather faint; color rather light canary and slightly turbid;
odor strongly urinous but normal; specific gravity 1025.43;
no abnormal matters; decomposed rather rapidly; micro-

PROLONGED MUSCULAR EXERCISE

371

scopical examination showed a rather unusual quantity of
mucus, otherwise negative.

Urea

Chlorin

Sulphuric acid

Phosphoric acid (total)

Phosphoric acid (with alkalis) * . .
Phosphoric acid (with earths) *. .
Uric acid

Per fluidounce.

5.800 grains.

3.360

1.440

0.960

0.640

0.320

0.680

Per hour

7.975 grams.

4.620

i.gSo

1.320

0.8S0

0.440

0.935

In 24 hours.

191.400 grains.

110.880 "

47.520 "

31.680 "

21.120 "

10.560 "

22.440 "

Table III. — comparison of the urine passed under

ORDINARY CONDITIONS (rEST) WITH THE URINE
PASSED DURING THE WALK OF ONE HUNDRED MILES
IN TW^ENTY-TW^O HOURS (eXERCISE)

PER HOUR.

IN TWENTY-FOUR HOURS.

Rest.

Total quantity. .

Urea

Chlorin

Sulphuric acid. .
Phosphoric acid!

(total)

Phosphoric acid

(with alkalis).
Phosphoric acid

(with earths). .
Uric acid

1.375 oz.
7-975 grs
4.620
1.980

1.320

0.880

0.440
0.935

Exercise.

Rest.

3.341 oz. 33.000 OZ. 80,
19.307 grs. 191.400 grs. 463

Exercise.

3-742
3074

5.025

4-275

0.750
1.670

lio.Sbo
47-520

31.680

21.120

10.560
22.440

89

73

120

102

18
40

000 OZ.

368 grs.
808 '
776 '

600 '

.600 '

000 '
.080 '

Percentage of
difference.

142.424

142.094

19.004

55-252

J280.681
j 365. 800

70.454
78.609

decrease,
increase.

The foregoing tables show the effects of prolonged
muscular exercise upon the general process of disassimila-
tion, as indicated by the elimination of effete matters by
the kidneys; and this is all the more marked as the exertion
probably reached to near the limit of endurance. By
reference to Table III. it will be seen that the variations
under repose and exercise are very great. It was impos-
sible to compare two specimens of the urine of the twenty-
four hours taken under conditions of diet precisely iden-
tical, which would have made the observations upon the
effects of muscular exercise much more satisfactory; but
physiologists are now sufficiently familiar with the effects

* Approximative.

372 PROLONGED MUSCULAR EXERCISE

of diet upon the composition of the urine to enable them
to separate tliese influences and appreciate the modifica-
tions produced l)y tlie great strain upon the muscular
system. I shall proceed, therefore, to consider these
changes, taking into account the disturbing influences of
the variations in the food and drink.

Total Quantity of Urine. — The quantity of water
in the urine was much greater during exercise, the excess
over the cjuantity passed under ordinary conditions
amounting to nearly one hundred and fifty per cent. This
I attribute in a measure to the excessive muscular exertion
and in part to the large quantity of liquids taken and the
fact that the skin did not act very freely. It is a fact that
an increase in the water of the urine, even when due entire-
ly to the ingestion of liquids, increases the absolute quantity
of solid matters excreted.

Urea. — The most interesting point in connection with
these investigations relates to the excretion of urea; and in
considering this it will be necessary to consider the influ-
ence of diet. By reference to Table IL, which gives the
composition of the urine under ordinary conditions, it will
be seen that the proportion of urea is smaller than one
would expect, judging from the specific gravity, but that
the chlorides are largely in excess. The total quantity in
the twenty-four hours is very small, hardly two hundred
grains. On inquiry, I ascertained that Weston is a small
eater; and on that day he ate but twice, slept twelve hours
and took very little exercise. His diet, also, on that day
contained but little nitrogenous matter. These facts
taken in connection with his weight, which was but one
hundred and twenty-two pounds, in part account for the
small quantity of urea.

On the day of the walk the elimination of urea was
enormous in proportion to the weight of the body, amount-
ing to four hundred and sixty-three grains, nearly one and
a half times more than on the day of repose. The question
here arises as to how far this is due to conditions of diet,
and what proportionate increase is to be attributed to the
great muscular exertion:

I. The excess of water eliminated by the kidneys would
account for a small part, but only a small part, of the in-
crease of urea.

PROLONGED MUSCULAR EXERCISE 373

II. The diet on the day of the walk contained a large
amount of nitrogenous matter; among other articles, six-
teen to eighteen raw eggs. This will account for a con-
siderable proportion of the excess of urea; and it remains
to see how much can reasonably be referred to this source.

III. The most complete series of observations upon the
effects of nitrogenous food on the elimination of urea are
those of Lehmann.* In these observations, made on his
own person, Lehmann found that he excreted, on a well-
regulated mixed diet, 501.6 grains of urea in twenty-four
hours. On a purely animal diet, taking, as one item, thirty-
two eggs, he excreted 821 grains, an excess of nearly sixty-
four per cent. In the case of Weston, who took about half
the number of eggs, there was an excess of one hundred
and forty-two per cent., leaving an excess, due to his long-
continued exertion', of seventy-eight per cent. Lehmann
also found that while he took in the eggs 465.5 grains of
nitrogen, he discharged only 387.8 grains of nitrogen in the
urea.

I do not propose to discuss critically the many observa-
tions that have been made within the last few years on the
influence of muscular.exercise, conjoined with peculiar diet,
upon the elimination of urea. So far as I know, on no
occasion has this point been investigated when the mus-
cular exertion has been so severe and prolonged. There
can be hardly any doubt that in the case of Weston the
feat of endurance which he accomplished increased the
elimination of urea by seventy-five or a hundred per cent.

Chlorides. — During the walk the chlorides in the
urine seemed to be below the average, while they were in
excess for the day of repose. The influence of the exercise
on the proportion of chlorides does not seem to be very
marked. On the day when the normal urine was taken,
the diet included a considerable quantity of salt in the
corned beef, and on the day before, salt ham was taken at
3 p. M., three hours before the urine was collected. The
variations in the chlorides may possibly be accounted for
by the diet.

Sulphates and Phosphates. — The total quantity of
sulphates was considerably increased during the day of the

* Lehmann, " Physiological Chemistry," Philadelphia, 1855, vol. i., p. 150 f^ seq.

374 PROLONGED MUSCULAR EXERCISE

walk. This is in accordance with all observations on this
point.

The proportion of phosphates on the day of the walk
was nearly quadrupled. This is a very interesting fact, as
the phosphates constitute a large and essential part of the
inorganic constituents of the tissues. A part of the great
excess was probably due to the muscular exertion and
want of sleep, and a part to the large preponderance of
animal food.

Uric Acid. — The muscular exertion increased, by
about seventy-eight per cent., the elimination of uric acid;
but the proportion per lluidounce was less during the exer-
cise than in repose. The theory has been advanced that
exercise increases urea and diminishes uric acid, the latter
undergoing oxidation more rapidly. My observations are
not conclusive on this point. The diminution in the pro-
portion of uric acid per fluidounce would seem to show that
oxidation was more rapid under exercise, the immense in-
crease in urea being also an argument in favor of this view.

In conclusion, these observations seem to show that
excessively severe and prolonged muscular exercise in-
creases largely the quantity of nitrogenous excrementi-
tious matters eliminated in the urine, particularly urea,
and produces a corresponding increase in the elimination
of most of the inorganic salts.

XIX

ON THE EFFECTS OF SEVERE AND PRO-
TRACTED MUSCULAR EXERCISE ; WITH
SPECIAL REFERENCE TO ITS INFLUENCE
ON THE EXCRETION OF NITROGEN

Published in the " New York Medical Journal" for June, 1871.

PART I

In May, 1870 I had an opportunity of examining the
entire urine passed by Weston, the pedestrian, during the
time occupied in accomphshing the feat of walking one
hundred miles in twenty-one hours and thirty-nine min-
utes. The urine on that occasion happened to have been
passed into a single vessel and had been undisturbed until
it came into my possession. I had no means of obtaining
any reliable scientific information in regard to the quantity
and character of the food taken during that time, nor had
I obtained, for purposes of comparison, a specimen of the
urine passed on the day before this muscular effort. It
was several weeks, indeed, before I could get the urine
of twenty-four hours of comparative repose; which I was
forced to take as representing the normal excretion. I
simply took the material for scientific analysis as I could
best obtain it and published the results with a statement
of the facts, not at that time entertaining any definite hope
of being able to repeat the investigations under more
favorable conditions. I was, of course, well aware of the
necessity of carefully estimating certain constituents of the
food, and of comparing the elimination of efifete matters,
particularly those containing nitrogen, with the matters
ingested. Had I been sure of an opportunity to study
the effects upon excretion of excessive and prolonged mus-
cular exercise, such as has since presented itself, my first

375

376 EXCRETION OF NITROGEN

experiments, of the unavoidable defects of which no one
could be more sensible than 1, would not have been
published. My first observations have been excluded in
the present inquiry on account of the imperfect data on
which they were based; but 1 may anticipate my conclu-
sions from these more complete experiments far enough
to state that the results have been essentially the same.

In the summer of 1870 Weston proposed to make an
attempt to walk four hundred miles in five consecutive
days and upon one of those days to walk one hundred and
twelve miles in twenty-four consecutive hours. He offered
to submit himself to any scientific observations that I
might wish to undertake in connection with this effort.
This offer was accepted; and I have endeavored to make
this occasion to the fullest extent useful to physiological
science. The investigations to be made seemed to me of
such importance, particularly in the present unsettled state
of opinion upon some points connected with nutrition
and disassimilation, that I asked the aid of certain well-
known scientists, in formulating and carrying out a series
of experiments which should be as complete as possible.

The following gentlemen consented to lend to the pro-
posed work the advantage of their scientific experience
and judgment: Dr. R. Ogdcn Doremus, Professor of
Chemistry in the Bellevue Hospital Medical College and
in the College of the City of New York; Dr. J. C. Dalton,
Professor of Physiology in the College of Physicians and
Surgeons; and Dr. W. H. Van Buren, Professor of the
Principles of Surgery, etc., Dr. Austin Flint, Professor of
the Principles and Practice of Aledicine, and Dr. Alexan-
der B. Mott, Professor of Surgical Anatomy, all of the
Bellevue Hospital ]\Iedical College.

At a meeting held some weeks before the walk a definite
plan of investigations was agreed upon. Prof. Doremus
assumed the responsibility of all of the necessary chemical
analyses, and I proposed to take charge myself of the re-
maining scientific work and to superintend the records of
diet, etc. The plan of operations agreed upon will be fully
detailed farther on, as an introduction to an account of
our observations; but this may be anticipated at the outset
by a few general statements.

It was proposed to make our observations for three

EXCRETION OF NITROGEN

377

distinct periods; viz., first period, five days before the walk;
second period, the five days of the walk; third period, five
■days after the walk. For the fifteen days during which
Weston was to be under observation, it was proposed to
have a trusty assistant with him every instant, day and
night, who was to weigh his food and drink and make notes
under the direction of one of our number. This was done
by Mr. Thomas C. Doremus, Jr., who performed his task
in the most faithful and accurate manner. The urine and
feces were sent to the laboratory of Prof. Doremus, where
they were analyzed under his direction by his assistant,
j\Ir. Oscar Loew. The necessary analyses of food were
also made by Mr. Loew.

The material thus collected, with a complete record of
the walk, finally passed into my hands for classification
and analysis. Before this report was written, the tables of
food, composition of urine, feces, etc.. were calculated.
This alone has been a labor of several weeks, and no pains
has been spared to secure entire accuracy. The numerical
calculations were all made by two or more different
methods, so that it has seemed almost impossible that any
error of importance should have been overlooked. Tak-
ing, as I have, the bare records and analyses made by ]\Ir.
Doremus and Mr. Loew, with entire ignorance of their
probable results, the calculations proceeded steadily to
their mathematical conclusions, which were apparent only
at the time of their actual completion.

In the preparation of this paper I have attempted to
present the scientific data in such a form as to be easily
available as ascertained facts, to any who may not admit
the interpretation I have put upon them.

It may serve to make the bearing of our observations
more easily comprehended to give a succinct statement of
the generally-received physiological views regarding cer-
tain of the points involved. In this I do not propose to
analyze the literature of the subject, even for the past few
years; and I desire especially to avoid controversial dis-
cussion. I do not intend to criticise the experiments of
others or to point out their defects, except in so far as
these defects may seem to be supplied by my more ex-
tended opportunities for investigations in particular direc-
tions.

25

378 EXCRETION OF NITROGEN

VIEWS OF PHYSIOLOGISTS IN REGARD TO THE INFLU-
ENCES OF EXERCISE, DIET, ETC., UPON THE ELIMINA-
TION OF NITROGENOUS EXCREMENTITIOUS MATTERS,
CHIEFLY UREA

Following the researches of Lavoisier on the chemical
phenomena of respiration and their relations to animal
heat, the theories of Liebig, who divided the food into two
classes, plastic and calorific, were almost universally ac-
cepted by physiologists. Liebig advanced the view that
the articles of food composed of carbon, hydrogen and oxy-
gen, were chiefly if not entirely useful in maintaining the
animal temperature, by entering into combination with the
oxygen of the inspired air, producing carbonic acid, water
and heat. He regarded the food composed of carbon,
hydrogen, oxygen and nitrogen as concerned chiefly, if
not entirely, in repairing the waste of the nitrogenous parts
of the living body, particularly the muscular tissue. Apply-
ing these views to muscular action, Liebig assumed that
exercise was always attended with an increased activity in
the destructive metamorphosis of the nitrogenous sub-
stance of the muscular tissue; and that this could be meas-
ured by the quantity of urea excreted. The following is
a quotation from one of his earlier works:

" Boiled and roasted flesh is converted at once into blood ;
while the uric acid and urea are derived from the metamorphosed
tissues. The quantity of these products increases with the rapidity
of transformation in a given time, but bears no proportion to the
amount of food taken in the same period. In a starving man, who
is any way compelled to undergo severe and continued exertion,
more urea is secreted than in the most highly-fed individual if in
a state of rest." *

Again, Liebig makes the general statement that " the
amount of tissue-metamorphosis in a given time may be
measured by the quantity of nitrogen in the urine." f

For many years this view of the source of the nitro-
genous excrementitious matters and the laws which reg-
ulate the activity of their production was received by
physiologists almost without question. It was modified,
however, a few years later by the researches of Lehmann;
who showed by a large number of observations on his ow^n

* Liebig, " Animal Chemistry, or Chemistry in its Applications to Physiol-
ogy and Pathology," London, 1843, p. 138. \ Ibid., p. 245.

EXCRETION OF NITROGEN

379

person that, other conditions being equal, the character
and quantity of food modified very greatly the elimination
of urea, as is seen in the following quotation:

" My experiments show that the amount of urea which is ex-
creted is extremely dependent on the nature of the food which has
been previously taken. On a purely animal diet, or on food very
rich in nitrogen, there were often two-fifths more urea excreted
than on a mixed diet; while, on a mixed diet, there was almost
one-third more than on a purely vegetable diet; while, finally, on a
non-nitrogenous diet, the amount of urea was less than half the
quantity excreted during an ordinary mixed diet." *

Lehmann further states, however, that upon a uniform
diet the elimination of urea is increased by muscular ex-
ercise.

The views of Liebig, modified by the researches of Leh-
mann, were pretty generally accepted up to 1866; not-
withstanding that Bischoff had advanced experiments to
show that the elimination of nitrogen by the kidneys was
regulated almost entirely by the quantity of nitrogen in
the ingesta.f

In 1866 Fick and Wislicenus published an account of
experiments made in ascending one of the Alpine peaks,
the Faulhorn, about 6,500 feet high. These experiments
were undertaken with the view of showing that severe and
prolonged muscular effort could be accomplished upon
a non-nitrogenous diet. The two experimenters took
no proteid food from midday on August 29 until 7 p. m.
of August 30. The experiments proper began on the
evening of the 29th, at a quarter past 6 p. m., with a
complete evacuation of the bladder. The urine from this
time till ten minutes past five on the morning of the 30th
(about eleven hours) was collected and called the " night-
urine." The ascent began at ten minutes past five and
occupied eight hours and ten minutes. The urine passed
during this period was collected as " work-urine." The
urine for five hours and forty minutes after the ascent
w'as collected as " after-work urine." The urine from 7
p. M., August 30 till half-past five a. m., xA.ugust 31 w-as

* Lehmann, " Physiological Chemistry," Philadelphia, 1855, vol. i., p. 150.

f Bischoff, " Der Harnstoff als Maas des Stoffwechsels," Giessen, 1853. In
i860 these researches were considerably extended by Bischoff and Voit,
Bischoff und Voit, " Die Gesetze der Ernahrung des Fleischfressers," Leipzig
und Heidelberg, i860.

38o EXCRETION OF NITROGEN

collected and designated as " night-urine." The results
of the examinations of these specimens in the two persons
were nearly identical. The following is the estimate of the
elimination of nitrogen per hour during the different
periods: *

Fick. Wislicenus.

During the night, 29th to 30th. . 0.63 grammes. 0.61 grammes.

During the time of work 0.41 " o-39 "

During rest after work 0.40 " 0.40 "

During the night, 30th to 31st. . 0.45 " 0.51 "

From these results Fick and Wislicenus conclude that
muscular exercise does not necessarily increase the elimi-
nation of nitrogen; that the substance of the muscle itself
is consumed in insignificant quantity; and that the mus-
cular system is a machine, consuming in its work, not its
own substance, but fuel, which is supplied by the food.
The most efficient fuel Fick and Wislicenus consider to
be non-nitrogenous food; the results of its consumption
being force, or work, heat and carbonic acid. They adopt
the view " that the substances, by the burning of which
force is generated in the muscles, are not the albuminous
constituents of the tissues, but non-nitrogenous substances,
either as fats or hydrates of carbon."

"We might express this doctrine by the following simile: A
bundle of muscle-fibres is a kind of machine consisting of albumi-
nous material, just as a steam-engine is made of steel, iron, brass,
etc. Now, as in the steam-engine coal is burnt in order to pro-
duce force, so, in the muscular machine, fats or hydrates of carbon
are burnt for the same purpose. And in the same manner as the
constructive material of the steam-engine (iron, etc.) is worn away
and oxidized, the constructive material of the muscle is worn away,
and this wearing away is the source of the nitrogenous constitu-
ents of the urine. This theory explains why, during muscular
exertion, the excretion of the nitrogenous constituents of the urine
is little or not all increased, while that of the carbonic acid is
enormously augmented ; for, in a steam-engine, moderately fired
and ready for use, the oxidation of iron, etc., would go on tolerably
equably, and would not be much increased by the more rapid firing
necessary for working, but much more coal would be burnt when
it was at w^ork than when it was standing idle."t

I have made these quotations from the paper of Fick
and Wislicenus for the reason that the theories advanced

* Fick and Wislicenus, " On the Origin of Muscular Power." — " London,
Edinburgh and Dublin Philosophical Magazine," London, January-June, 1866,
vol. xxxi., p. 492. ■)• Loc. cit., p. 501.

EXCRETION OF NITROGEN 381

and the experiments reported have changed very materially
the current of physiological opinion in regard to the ori-
gin of muscular force and the significance of the elimina-
tion of nitrogen. The question is not materially modified
or advanced by the papers of Frankland * or of Haughton.f
who sustain fully the views of Fick and Wislicenus, which
are now adopted very largely, particularly in Germany and
England.

The opposite view, that the elimination of nitrogen is
to a great extent a measure of the waste of the nitrogenous
constituents of the tissues and that this is increased by
exercise, is substantially the one advanced by Liebig. Al-
most all observers who have experimented on the influence
of exercise upon the elimination of urea, under an ordinary
diet, have found its excretion markedly increased. In
1867 experiments were made by Parkes upon two soldiers,
with the view of controlling the experiments of Fick and
Wislicenus by observations upon a more extended scale. :{:
These experiments failed to confirm those of Fick and
Wislicenus. They were continued for a period of eighteen
days and certainly seemed to show an increase in the urea,
attributable to muscular exercise. The extraordinary ex-
ercise taken was a walk of 23.70 miles on one day and
32.78 miles on the day following. During these two days,
on an exclusively non-nitrogenous diet, the elimination of
nitrogen was slightly increased over a period of two days
of rest and non-nitrogenous diet. In an analysis of a recent
course of lectures delivered by Dr. Parkes at the College
of Physicians, London, it appears that he is disposed to
take a view of the subject between the two extremes; viz.,
that the muscular system is able to accomplish work by the
consumption of non-nitrogenous food; that exercise does,
however, slightly increase the elimination of urea and that
during exercise a small portion of the muscular substance
is consumed; but he is of the opinion that the variations

* Frankland, " On the Origin of Muscular Power." — " London, Edinburgh
and Dublin Philosophical Magazine," London, July-December, 1866, vol.
xxxii. p. 1S2, et seq.

\ Haughton, " Address on the Relation of Food to Work done by the Body,
and its Bearing upon Medical Practice." — " The Lancet," London, August 15,
August 22, and August 2g, 1868.

X Parkes, "On the Elimination of Nitrogen by the Kidneys and Intestines,
during Rest and Exercise, on a Diet without Nitrogen." — "Proceedings of the
Royal Society," London, 1S67, vol. xv.. No. 89, p. 339 et seq.

3S2 EXCRETION OF NITROGEN

in the (juantity of nitrogen eliminated are almost entirely
dependent upon the quantity of nitrogen contained in the
food.*

One desirous of consulting further the literature of this
question may find, in a recent article by Liebig, a full dis-
cussion of the subject of the source of muscular power from
his own point of view.f He analyzes very fully the ex-
periments of Parkes, and he finds in the results fresh testi-
mony in favor of his view that the increase in the elimina-
tion of nitrogen as a consequence of muscular exercise is
not limited to the period of exertion but continues for some
time after. On the other hand, Voit has lately published
an elaborate paper reviewing the publications on this ques-
tion that have appeared during the last twenty-five years. :|:
Neither of these papers adds to the sum of physiological
knowledge l)y the contribution of new experimental facts;
but they are interesting as expressing the arguments upon
two opposite sides, and they illustrate the necessity of new^
observations, in which some of the important omissions in
the experiments hitherto made may be supplied.

PLAN OF THE INVESTIGATIONS AND THE PROCESSES
EMPLOYED

A few weeks before Weston put himself under our
observation, he was made to undergo a thorough physical
examination at the hands of Prof. Austin Flint, and his
urine was examined by myself. The result showed that
Weston was in perfect health, at least so far as could be
determined by any ordinary physical examination. This
examination was made in order to ascertain whether or
not there existed any physical reason why it would be
unsafe for Weston to undertake his proposed task.

Having ascertained that Weston was in perfect health,
he was invited to be present at a meeting for the purpose
of fixing upon a definite plan of investigation. At this
meeting were present. Profs. Doremus, Dalton,Van Buren,

* " Abstract of the Croon ian Lectures delivered at the College of Physicians
by Dr. Parkes." — " Medical Times and Gazette," London, March 15, iSyi.p. 348.

f Liebig, " The Source of Muscular Power." — " The Pharmaceutical Jour-
nal and Transactions," London, 1S70, Third Series, part ii., p. 161, and part
lii., pp. 181, 201, 221.

i Voit, " Ueber die Entwicklung der Lehre von der Quelle der Muskel-
k:raft und einiger Theile der Ernahrung seit 25 Jahren." — " Zeitschrift fiir
Biologic," MUnchen, 1870, Bd. vi., S. 305 et seq.

EXCRETION OF NITROGEN 383

Flint and myself. Weston was here subjected to another
examination with reference to his physical condition, which
was found to be perfect.

As the result of our deliberations at this meeting it was
decided to confine our investigations within limits that
would render it possible to complete them accurately and
satisfactorily; the fear being that in attempting to do too
much the value of our results might be impaired. It was
also deemed proper to take the position that we would
under no circumstances interfere with Weston's diet, train-
ing or manner of making the walk, simply observing the
facts according to our plan. This was fully carried out.
Throughout the entire fifteen days during which Weston
was under observation, he acted in everything according
to his own judgment; and the walk was made without any
advice or interference on the part of any of those engaged
in the investigations.

In collecting our material it was determined to note
the following points:

I. To take our observations during three periods; viz.,
a first period, five days before the walk; a second, the five
days of the walk; and a third, five days after the walk. In-
asmuch as we proposed to assume the entire responsibility
of the accuracy of all the facts noted, it was determined to
place Weston in the hands of Mr. Thomas C. Doremus, Jr.,
son of Prof. Doremus, who was not to leave him, night or
day, without notifying the person in charge of the investi-
gations. ]\Ir. Doremus was actually with Weston, night
and day, for the fifteen days, except on two occasions.
On one day, for a few hours. Mr. Doremus' place was sup-
plied by Mr. Loew, assistant to Prof. Doremus, who was
engaged in making the chemical analyses. On another
occasion, Mr. Doremus was relieved by me for about four
hours. During the walk. Prof. Mott, Prof. Doremus and
I, one or all of us, were constantly present at the rink.
]\Ir. Doremus was with Weston almost constantly at this
time, but he occasionally slept in the building, when Wes-
ton was walking at night, leaving him in charge of one of
us. It is necessary to make these statements, in view of
the extraordinary character of our results, to show that
nothing is taken as a fact to work upon unless obser\^ed
by ourselves or our assistants.

3S4 EXCRETION OF NITROGEN

II. To take every day, as nearly as possible at the same
hour and under the same conditions, the naked weight,
})nlse, respirations and temperature.

III. To note accurately the weight of every separate
article taken as food or drink. This was done for two pur-
poses: to note the ingesta and excreta, with reference to
the weight of the body; and to have all the articles of food
separately weighed, so as to estimate the daily consumption
of nitrogen.

IV. To note the amount of exercise taken each day,
in the first period, before the walk, and in the third period
after the walk; and also to note anything unusual with
reference to his general condition.

V. To collect the entire urine of the twenty-four hours,,
day by day, for the purpose of subjecting it to chemical
and microscopical examination. As Weston proposed to
arrange in his walk of five days that the time should expire
a few minutes after midnight, the twenty-four hours for
collecting the urine were calculated from midnight to mid-
night. It was also decided to collect and w'eigh the feces.

In the execution of the above plan I assumed the re-
sponsibility of superintending the records, except the notes
of the chemical analyses, and of making microscopical ex-
aminations of the urinary sediments. Prof. Doremus as-
sumed the responsibility of the chemical analyses. So far
as the general records are concerned, I have no hesitation
in testifying to their entire accuracy. It is fortunate that
no accident happened, such as the breaking of a bottle or
a glass, and the only error was in taking the weight on
November 23, the third day of the walk. Prof. Doremus
is equally satisfied in regard to the chemical analyses made
by his assistant, Mr. Oscar Loew\

The details of the plan as it was carried out are as fol-
lows :

Mr. Doremus, Mr. Loew and I were each provided
with a notebook. My own notebook was for recording
the microscopical examinations of the urinary sediments.

The following directions were written in the notebook
given to Mr. Doremus:

At ever\^ meal weigh the food and drink in the follow-
ing manner:

Put the meat on a separate plate and weigh the plate

EXCRETION OF NITROGEN 385

before and after eating. Note the loss of weight, which will
give the quantity actually consumed. Weston does not
intend to eat much fat, but expects to get his fat from
butter. When he eats fat it is to be noted.

Put each vegetable on a separate plate and determine
the quantity consumed, in the same way as for the meat.

Estimate the bread in the same way as the meat and
vegetables.

Take a known weight of butter and weigh each night
to ascertain the quantity taken during the day. It will be
sufficient to determine in this way the quantity of butter
consumed in the twenty-four hours.

Estimate the quantity of sugar taken, in the same way
as for the butter.

Note the number of eggs taken and see that they are
entirely consumed.

Measure the water taken, by fluidounces. and always
carry a graduated glass for Weston to drink from, so
that the quantity shall be taken exactly.

Measure the coffee, tea and any other liquids taken, in
the same way, and note especially the quantity of milk
used.

Each night, just before Weston goes to bed, take
the weight of the body, naked, the temperature under the
tongue, the pulse and respirations, and note the time when
the above-mentioned conditions are observed. The pulse
is always to be counted sitting. The respirations are to
be taken in the same position, when Weston's attention is
diverted and when he is perfectly tranquil.

Note the exercise, miles walked, time, etc., for each
twenty-four hours.

Collect all the urine for each twenty-four hours. Send
six fluidounces to me for microscopical examination and
send the remainder to the chemical laboratory for quantita-
tive analysis. Before any of the urine is sent, mix the whole
for the twenty-four hours and note on the bottle sent to
the chemical laboratory the quantity taken out for micro-
scopical examination, so that the chemist may take this into
account in his record of the entire quantity.

Collect the feces and send them each day to the chem-
ical laboratory.

At the end of each record for the day, note the general

386 EXCRETION OF NITROGEN

condition of health and feehngs and any unusual circum-
stance that may have occurred during the day affecting the
physiological conditions.

Note each fact instantly, leaving nothing to the memory.
Read these directions carefully every night before closing
the record for the day and supply at once any omissions.

The following directions were written in the notebook
given to Mr. Loew:

Measure the entire quantity of urine in the twenty-four
hours.

Note the odor, color, reaction and specific gravity.

Note the presence or absence of albumin or sugar.

Ascertain the proportions of various constituents of the
urine, according to directions received from Prof. Dore-
mus.

Be careful to note each day accurately from midnight
to midnight.

The weight was taken each night, generally in my pres-
ence, by Mr. Doremus, as near midnight as practicable,
upon new platform-scales, weighing accurately to a quar-
ter of a pound. The food was weighed upon a new balance,
weighing accurately to iz of an ounce. These balances
were selected on account of their accuracy and their avail-
ability for rapid weighing, inasmuch as it was desirable to
annoy Weston as little as possible, particularly in giving
him his w-eighed food. The pulse, respirations and tem-
perature w^ere noted by me, except on the evening of No-
vember 1 6th, when they were noted by Prof. Dalton. The
temperature was taken under the tongue with a maximum
thermometer, graduated to ro of a degree Centigrade.

The weight of the food w^as taken in the manner indi-
cated. The liquids were measured in a graduated glass,
as a matter of convenience; but their weights were calcu-
lated in the final tables.

Having taken the weight of each article of food, it was
•desired to ascertain the quantity of nitrogen in the ingesta.
After consulting the works at my command giving analyses
of different articles of food, I compiled the following table
from Payen. It was at first thought desirable to subject
specimens of each article to analysis for nitrogen; but the
conditions under which the observations were carried out
seemed to render the estimates of Payen quite as useful.

EXCRETION OF NITROGEN 387

It was assumed at the outset that we were not to interfere
with the diet in any way, noting only the articles taken,
Weston's food was taken at several different places and
was prepared by different persons; and it would have been
impossible to have analyzed actual specimens of each arti-
cle. In view of this fact, it seemed probable that the varia-
tions from our analyses, should we have made them, would
have been as considerable as the variations from the average
estimates given by Payen. It has been ascertained, also,
that the flesh of different animals presents but a small frac-
tion of a percentage of difference in the nitrogen. All the
meats, therefore, are classed together in the table and are
assimilated to the composition of cooked beef, which con-
tains about 3.5 per cent, of nitrogen.* No estimate could
be found of the proportion of nitrogen in the beef-essence,
head-cheese or oatmeal-gruel; and these articles were ana-
lyzed for nitrogen by Mr. Oscar Loew, by the ordinary
method; viz., treating the dry residue after evaporation with
soda-lime and determining the nitrogen as ammoniochlo-
ride of platinum, reducing the metallic platinum by heat.
The estimates of the proportions of nitrogen in the food
were therefore approximative; but the percentage that
might properly be allow^ed for error would be very slight.
Even if this should be taken at the almost impossible figure
of ten per cent., it would not modify the results. The ad-
vantage of experimenting upon a normal and unrestricted
diet seems to me to more than compensate for the neces-
sarily approximative estimates of the quantities of nitrogen
consumed.

Proportions of Nitrogen per Hundred Parts

Article. Nitrogen. Authority.

Beef . . . ] f

MuUon. I I Payen, p. 488. This is the

Chicken !• 3.50 <] approximative estimate

Turkey, j | for cooked beef.

Fish ... J I

Eggs 1 .90 Payen, p. 488.

Beef-essence 0.87 O. Loew (actual analysis).

Head-cheese 2.24 " "

Milk 0.66 Payen, p. 488.

Custard 1.28 Average of milk and eggs.

* Payen, " Precis theorique et pratique des substances alimentaires," Paris,

1865, p. 48S et seq.

388

EXCRETION OF XITROGEX

Authority.
Average of milk and eggs.

Payen, p. 489.

1.08 Payen, p. 490.

" ; Rice, p. 180.
O. Loew Tactual analysis;.

Pav

en, p. 490.

Article. Nitrogen.

Ice-cream 1.28

Cream-cakes 1.28

Oysters 2.13

Cheese 4. 1 2

Bread (includes corn-cakes,
cake, crackers and bread-
pudding 1

Rice-pudding (rice and custard) 1.18

Oatmeal-gruel 0.086

Potatoes 0.33

Figs 0.92

Butter 0.64

Coffee o. II

Tea 0,02

Tomatoes

Cranberries

Cauliflower

Celer\-

Lettuce

Tomato-soup

Tomato-catsup

Grapes

c^fon These anicles contain no nitrogen or merely a

p' ' ■ ■ trace which may be disregarded.

Sweet pickles

Sugar

Lemonade

Molasses-and-water .

"\'inegar

Salt

Pepper

Bicarbonate of potash

The urine of each twenty-four hours was carefully col-
lected in a large glass-stoppered bottle and was analyzed
by Mr. Loew by the following methods:

The specific gravity was always determined by actual
weight.

The urea was estimated by Liebig's volumetric process.
In this, a single specimen of urine was used for estimating
both chloride of sodium and urea. The chloride of sodium
was determined first, and afterward the urea was deter-
mined with a different mercurial solution. This was done
to avoid confusion and possible mistakes in the readings
of the burettes.

The uric acid was determined by weight; concentrating
the urine, treating it for twelve hours with nitric acid, and
collecting the cr^-stals of uric acid.

EXCRETION OF NITROGEN 389

The phosphoric acid was determined by weight, con-
verting the phosphates into j\l9HP04 + 7H2O.

The sulphuric acid was determined by weight, convert-
ing the sulphates into BaS04.

The examination of the urinary sediments was made
by myself with a i inch objective, allowing the specimen
to stand for about twelve hours.

The feces were passed directly into clean glass vessels
provided with air-tight glass covers, and weighed. The
nitrogen of the feces was estimated by the soda-lime and
platinum process.

PHYSIOLOGICAL HISTORY OF WESTON FOR THE FIFTEEN
DAYS DURING WHICH HE WAS UNDER OBSERVATION

The fifteen days during which \\'eston was under ob-
servation were divided into three periods of five days each.
During the first period of five days, he took very moderate
exercise and assumed to be " training " for the walk, though
he did not pursue the system generally adopted in training
for feats of endurance. The second period embraces the
five days of the walk. The third period of five days after
the walk was one of almost absolute rest. During the
entire fifteen days he abstained altogether from alcoholic
beverages. Though not what is called a total abstainer,
Weston is not an habitual drinker. He occasionally takes
a glass of ale or wine, but this is rare. During the first
two periods Weston did not smoke. He smoked five to
seven cigars daily during the third period of five days. In
the records of food taken, the time of eating is stated, but
I have not thought it necessary to extend the tables by
giving a separate account of each meal and shall generally
give in a single table the entire quantity consumed in the
twenty-four hours.

At the time of making the walk Weston was thirty-one
years and eight months old. His height is five feet and
seven inches. His ordinary weight, naked, is one hundred
and twenty to one hundred and twenty-five pounds. He
has never had any serious illness, with the exception
of what he describes as vertigo and rather serious brain-
symptoms after attempting a walk when he was suffering
from a cold and headache. This occurred in the summer

390 EXCRETION OF NITROGEN

of 1870. He does not know that he has any hereditary-
tendency to disease.

His general build is slight and the parts above the waist
are very light. The bones of the chest and upper extrem-
ities are small and the muscles are but little developed.
The pelvis is unusually broad for a male, and the lower
extremities are so formed that there is a considerable space
between the thighs from the knees to the perineum. The
lower extremities are remarkable for the unusual develop-
ment of the muscles that move the thighs upon the pelvis.
In walking, it is observ^ed that Weston makes great use of
these muscles and uses the muscles of the leg very little.
The calf of the leg is small; much smaller than one would
expect to see in a pedestrian.

A noticeable peculiarity about the muscles of the thighs
and legs is that they never become very hard. They were
quite soft before the walk, and at all times during the walk
they were in the same condition. It was very remarkable
that after the third day when Weston had walked within
the twenty-four hours ninety-two miles, the muscles were
as soft as ever. It has seemed to me that this peculiarity
of the muscles is advantageous. When the muscles are"
very hard from thorough training, prolonged exertion is
likely to produce cramps, due, perhaps, to exaggeration
of the normal muscular irritability. This is a difficulty ex-
perienced by pedestrians. In the case of Weston, the
movements were always free, and, according to his state-
ments, he w^as never much fatigued. Only once during
the five days of the walk did he say that he was " leg-
weary." What he complained of most was want of sleep,
and at one time, vertigo. The conformation of the feet
is perfect; the toes are straight, the instep is high, and the
heel is very long, giving a remarkable leverage for the
tendo Achillis. The heel does not project, as in the negro,
but the tendo Achillis passes straight to the calf of the leg.

The nervous element seemed to me very important in
the tasks accomplished by Weston. On the fourth day of
the w^alk, having made on the first day, eighty miles, on
the second, forty-eight miles, and on the third, ninety-two
miles, he kept on the track after having w^alked more than
fifty miles, until vertigo became so great that he could not
see to turn the corners. He was forced to abandon hope

EXCRETION OF NITROGEN 391

of making four hundred miles in five days; but on the fifth
day, he appeared again at 10 a. m., and walked more than
forty miles.

FIRST PERIOD, FIVE DAYS BEFORE THE WALK

At midnight, November 15, 1870, the observations
were begun. At forty minutes past twelve his general
condition was as follows:

Weight (naked) 120.5 lbs. (54 k. 655 grammes.)

Temperature under the tongue 98.6° (37° C).

Pulse (sitting and perfectly tranquil) 64.

Respirations 19.

Immediately after this examination Weston went to
bed.

NOVEMBER 1 6, FIRST DAY

Weston slept well during the night and rose in good
health and spirits at 8.15 a. m. He felt well the entire day;
took his breakfast at 9.15 a. m.; dinner at i.io p. m.; and
supper at 7.55 p. m. He walked during the day about
fifteen miles. Though feeling well he was worried and
anxious about the business arrangements for his walk. He
did not go to bed until 2.35 a. m., November 17. He
slept, during the twenty-four hours, seven hours and thirty
minutes.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Beefsteak 12.25 187.58

Mutton-chops 3.00 45-94

Eggs 2.76 22.94

Milk... 7.21 20.82

Bread 9.88 47.48

Potatoes 8.25 11-99

Butter 2. 1 2 5.94

Sugar 1.78 00.00

Coffee 3560 17-13

Tea 16.03 1.40

Water 24.00 00.00

Salt 0.09 00.00

Pepper 0.02 00.00

122.99 361.22

(3,492.17 grammes.) (23.404 grammes.)

Total ingesta (7 lbs., 10 jS^ oz.)

Liquids (5 lbs., 2-^%^ oz.)

392 EXCRETION OF NITROGEN

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 39.55 fl § (1,170.0 cc.)

Specific gravity 1024 o

Urea 650.08 grains, 42. 1 20 grammes.

Nitrogen in urea 303.37 " 19.656 "

Uric acid 3.55 " 0.230 "

Phosphoric acid 51.46 " 3-334 "

Sulphuric acid 38.37 " 2.486

Chloride of sodium 195.02 " 12.636 "

This urine presented a light flocculent sediment, which contained a
large number of octahedra of oxalate of lime.

FECES

Quantity 3.70 oz. av. 105.0 grammes.

Nitrogen 1 9.89 grains, i .289

Nitrogen in urea and feces combined . . 323.26 " 20.945 "

Nitrogen of urea and feces per 100 parts of nitrogen of food . . 89.49 parts.

Uric acid per 100 parts of urea 0-538 "

I Weight (naked) 120.5 lbs. (54 k. 655 grammes.)

J Temperature under the tongue 997° (37° C.)

I Pul.se, full and soft 75.

( Respirations 20.

10.30 P. M.

NOVEMBER 1 7, SECOND DAY

After going to bed at 2.35 a. m., Weston rose at 8.45
A. M. He had a little headache in the middle of the day.
He took breakfast at 9.40 a. m.; dinner at 2.30 p. m.; and
supper at 7.40 p. m. He walked during the day about
five miles. He went to bed at 11.30 p.m. He slept,
during the twenty-four hours, six hours and forty minutes.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av.

Nitrogen, in grains.

Beefsteak

525

80.39

Roast beef

5-25

4.14

80.39
3441

Eggs

Milk

463

13-37

Bread

8.50

40.16

Potatoes

10.00

14.44

Tomatoes (stewed) . . .

7.00

00.00

Butter

2.95

8.26

Sugar

1.25

00.00

Coffee

32.32

15-53

Tea

16.03

1.40

Water

8.00

00.00

Salt

0.02

00.00

Pepper

0.09

00.00

105.43 (2,987. 92 gms.) 288.35 (18.682 gms.)
Total ingesta (6 lbs., 9iVo o^.). Liquids (3 lbs., 12-^^ oz.).

EXCRETION OF NITROGEN 393

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 38.0303 (1,125.000.)

Specific gravity 1024.4

Urea 590-35 grains, 38.250 grammes.

Nitrogen in urea 275.50 " 16.517

Uric acid 4.03 " 0.261

Phosphoric acid 44.o8 " 2.921

Sulphuric acid 40.92 " 2.651

Chloride of sodium 1 58.00 " 10.237

The sediment was the same as on November 16, but the octahedra
of oxalate of lime were more abundant.

FECES

Quantity 4.78 oz. av. 135.5 grammes.

Nitrogen 25.68 grains, i .664

Nitrogen in urea and feces combined . . 301.18 " 18. 181 "

Nitrogen of urea and feces per 100 parts of nitrogen of food . 104.45 parts.

Uric acid per 100 parts of urea 0.683

r Weight (naked) 121.25 Ibs^ (55 kilos.)

I Temperature under the tongue 98.4° (36.9" C.)

j Pulse 73.

[ Respirations 20.

11.20 p. M.

NOVEMBER 1 8, THIRD DAY

Weston rose at 9 a. m.; took his breakfast at 9.50 a. m.;
dinner at 2.15 p.m.; and supper at 7.35 p.m. He said
he felt '* splendid " all day. He wrote about seven hours
and \valked about live miles. He ^vas very cheerful all
day and went to bed at 12.20 a. m., November 19. He
slept, during the twenty-four hours, nine hours.

Weights and Analyses of Food and Drink for the Twexty-

FOUR Hours

Beefsteak

Eggs

Milk

Bread

Potatoes

Butter

Sugar

Coffee

Tea

Salt

Pepper

Oz. Av.

Nitrogen, in grains

10.37

158.79

2.76

22.94

7.21

20.82

7-75

36.62

5-13

7-41

3-13

8.76

1-75

00.00

32.32

15-53

16.03

1.40

0.09

00.00

0.02

00.00

86.56 272.27

(2,453.67 grammes.) (17.641 grammes.)

Total ingesta (5 lbs., 6.r^ o^-^

Liquids (3 lbs., 7^ oz.)

26

394 EXCRETION OF NITROGEN

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 46.15 fl | (1,365.0 cc.)

Specific gravity 1023. i

Urea 653.08 grains, 42.315 grammes.

Nitrogen in urea 30477 " ^9-747

Uric acid 0.94 " 0.061 "

Phosphoric acid 45- H " 2.925

Sulphuric acid 38.86 " 2.518 "

Chloride of sodium 191.70 " 12.421

Tbere was a rather light cloudy sediment which contained a little
mucus and a very few small octahedra of o.xalate of lime.

FECES

Quantity 476 oz. av. 135.0 grammes.

Nitrogen 25.59 grains, 1.658

Nitrogen in urea and feces combined. . 330.36 " 21.405

Nitrogen of urea and feces per 100 parts of nitrogen of food. 121.30 parts.

Uric acid per 100 parts of urea o. 144 "

I Weight (naked) 120 lbs. (54 k. 432 grammes.)

I Temperature under the tongue 98° (36.7° C.)

11.55 P.M. j p^jgg ^j

[ Respirations. 20.

NOVEMBER IQ, FOURTH DAY

Weston rose at 8.35 a. m., feeling as well as possible;
took breakfast at 9 a. m. ; dinner at 4.45 p. m. ; and supper at
10.45 P- ^^- He said he felt " splendid " all day. He walked
during the day about fifteen miles, was very cheerful and
went to bed at 12.45 ^- M-» November 20. He slept, dur-
ing the twenty-four hours, seven hours and fifteen minutes.

Weights and Analyses of Food and Drink for the 24 Hours

Oz. Av. Nitrogen, in grains.

Beefsteak 4.25 65.08

Mutton-chops 4.88 74-72

Roast beef 4.88 74 72

Eggs 4.14 34.41

Milk 4.38 12.65

Bread 10.25 48-43

Potatoes 0.88 1.27

Butter 2.43 6.80

Sugar 1. 6 1 00.00

Coffee 32.32 15.53

Tea 16.03 I -4°

Salt 0.09 00.00

Pepper .... 0.05 00.00

86.19 335°^

(2,443.19 grammes.) (21.706 grammes.)
Total ingesta (5 lbs., 6^^^ 02. ). Liquids (4 lbs., 4j^ oz.).

EXCRETION OF NITROGEN 395

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 3245 fl § (960.0 cc.)

Specific gravity 1027.6

Urea 607.55 grains, 39.365 grammes.

Nitrogen in urea 283.52 " 18.370

Uric acid i .06 " 0.069 "

Phosphoric acid 67.00 " 4.341

Sulphuric acid. . 51.50 " 3-337 "

Chloride of sodium 106.68 " 6.912 "

This urine presented a copious fawn-colored sediment which cleared
up with gentle heat. It contained the amorphous urates with a large
number of octahedra of the oxalate of lime.

FECES

Quantity 3.17 oz. av. 90.0 grammes.

Nitrogen 17.05 grains, 1.105

Nitrogen in urea and feces combined.. 300.57 " 19-475 "
Nitrogen of urea and feces per 100 parts of nitrogen of food. 89.75 parts.
Uric acid per 100 parts of urea o. 1 74 "

Weight (naked), taken at 12.35 A.M., November 20, 118.5 (53 k. 745
grammes).

C Temperature under the tongue 99- 1° (37-3° C.)

11.55 P.M. < Pulse 78.

( Respirations 23.

NOVEMBER 20, FIFTH DAY

Weston rose at 10.45 ^- ^i-' feeling remarkably well.
He took breakfast at 11.30 a. m.; dinner at 5.55 p. m.; and
supper at 11. 15 p. m. He said he felt " splendid " all day.
He walked about one mile during the day. He started
on his walk at 12.15 a. m., November 21. He slept, during
the twenty-four hours, ten hours.

Weights ani? Analyses of Food and Drink for the 24 Hours

Oz. Av. Nitrogen, in grains.

Beefsteak 18.25 279.45

Eggs 6.90 57-35

Milk 11.33 32-71

Bread 8.88 41-96

Potatoes 3.00 4.43

Butter 2.75 7.70

Sugar 1.75 00.00

Coffee 32.32 15-53

Tea 16.03 I -40

Salt 0.08 00 00

Pepper 0.05 00.00

101.34 440-43

(2,872.63 grammes.) (28.536 grammes.)

Total ingesta (6 lbs., St^ o^.). Liquids (3 lbs., i i-/o\ o^.).

396 EXCRETION OF NITROGEN

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 34-00 fl | (1.050.0 cc.)

Specific gravity 1025.2.

Urea 640.13 grains, 41-475 grammes.

Nitrogen in urea 298.73 " 19.355

Uric acid 1-73 " 0-ii2

Phosphoric acid 43-Oi " 2.787

Sulphuric acid 38-18 " 2.474

Chloride of sodium 145-^5 " 9-450

This specimen of urine presented rather a faint cloudy sediment
which contained a large number of octahedra of the oxalate of lime.

FECES

Quantity 3-97 oz. av. 1 1 2.5 grammes.

Nitrogen 21.33 grains, 1.382

Nitrogen in urea and feces combined. . 320.06 " 20.737 "

Nitrogen of urea and feces per 100 parts of nitrogen of food. 72.67 parts.
Uric acid per 100 parts of urea 0.270 "

f Weight (naked) 1 19.2 lbs. (54 k. 62 grammes.)

J Temperature under the tongue 99-5° (37-5°Q

1 1.45 P. M. I p^jgg ^^

[ Respirations 25.

SECOND PERIOD, FIVE DAYS OF THE WALK

The walk took place in a large building of corrugated
iron, known as the " Empire Skating Rink," on Third
Avenue, near Sixty-fourth Street. This building is ob-
long, measuring 170 by 350 feet. A track made of boards
covered with dirt and fine shavings was laid out in the
form of a parallelogram. This track was measured by
Mr. Joseph L. T. Smith, surveyor, in the presence of Prof.
Doremus and myself. The circuit, taken two and a half
feet from the inside, measured 735to*o" feet. This measure-
ment was made with a metallic tape, adjusted for tempera-
ture and tested in our presence. In making the measure-
ment. Prof. Doremus was at one end of the tape and I
was at the other, and every reading was carefully verified.
Seven full circuits and i29TTnr additional feet made a full
mile. In computing the walk the distance was noted by
circuits. Three judges were in attendance day and night;
one calling the time of each circuit, and two checking off
the circuits in a book provided for that purpose. In addi-
tion, either Prof. Doremus, Prof. Mott or I was con-
stantly present. Weston had retiring-rooms in the front

EXCRETION OF NITROGEN 397

of the building, where his food was prepared, where he
slept and where our observations were taken. The dis-
tance from the judges' stand to the door of these rooms
was I45tVo feet.

During the walk Weston took but few regular meals,
a great part of his nourishment being taken while actually
walking. In this way he took beef-essence, soft-boiled
eggs, gruel, tea, cofifee and all other drinks. I shall not,
therefore, give the time of the meals taken during this
period, but simply state the entire quantity consumed in
each twenty-four hours.

In regard to the distance walked, we are all satisfied
that there is no room for doubt. But although the task
proposed was not accomplished, the effort was so great,
that I have thought it best to give the history of these five
days rather fully in detail.

NOVEMBER 21, FIRST DAY

The following is a summary of the twenty-four hours
of November 21 :

12 00 to 12 15 A. M. 15 minutes' rest before starting.
12 15 to 49 " 3 h. 54 m. wall<ing 20 miles, with 4 stops for uri-
nation, averaging 24 sec. eacli.

4 9 to 7 58 " 3 h. and 49 m. rest (sleep).

7 58 to 9 6 " I h. and 8 m. walking 5f miles.
9 6 to 919 " 13 m. for breakfast.

9 19 A. M. to I P. M. 3 h. and 41 m. walking 17 miles, with 5 m. 12 sec.
for defecation, and 2 stops for urination, aver-
aging 30 sec. each.

I 00 to I 46 " 46 m. for dinner.

I 46 to 325 " I h. and 39 m. walking 8 miles, with 2 stops for
urination, averaging 27^ sec. each.

3 25 to 3 32 " 7 minutes' rest, sitting on the track.

3 32 to 5 34 " 2 h. and 2 m. walking 9^ miles, with 2 stops for
urination, averaging 26J sec. each.

5 34 to 6 27 " 53 minutes' rest (supper).

6 27 to 8 38 " 2 h. and 11 m. walking 12 miles, with 3 stops for

urination, averaging 26 sec. each.

8 38 to 8 48 " 10 minutes' rest, sitting on the track.

8 48 to 10 32^ " I h. 444 m. walking 8 miles, with 2 stops for uri-
nation, averaging 32|- sec. each.
i0 32|-to 1200 " I h. 274 minutes' rest, continued into November
22, 4'h. 58 m.

During the 24 hours of November 21, Weston walked 80 miles in
16 h. and 20 m., including 5 m. 12 sec. for defecation and 6 m. 45 sec. for
urination. Deducting the time for defecation and urination, his walking-
time was 16 h. 8 m. and 3 sec, and he averaged a fraction less than 5

398 EXCRETION OF NITROGEN

miles per hour. He had 17 minutes' rest, sitting by the traci<, and 7 h.
and 23 m. for breakfast, dinner, supper and sleep. He urinated 15 times
on the track. He vomited a little liquid twice during the night at 10.50
and 1 1. 15. He slept, during the twenty-four hours, about i hour.

Walking 80 miles.. . . 16 h.

Defecation

Urination

Rest on the track. . . .
Rest off the track 7 h.

8 m.

3 sec.

5 "

12 "

6 "

45 "

17 "

23 "

23 h. 59 m. 60 sec. = 24 hours.

During the whole of the first day, Weston seemed to feel very well
and made his walk with ease. He was slightly nauseated at times, but he
said that he had always more or less disturbance of that kind when he
first began a walk.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Mutton-chops 2.00 30.62

Eggs 6.90 57.35

Milk 5.66 16.34

Bread 1.25 5.91

Butter 2.63 7.36

Sugar 1 .63 00.00

Coffee 67.67 32.57

Tea 16.03 1.40

Water 6.75 _ 00.00

Lemonade 71.16 00.00

Molasses-and-water .. 4.40 00.00

Salt 0.08 00.00

Pepper 0.05 00.00

Bicarbonate of potash . 0.04 00.00

186.25 151-55

(5,282.38 grammes.) (9.820 grammes.)

Total ingesta (11 lbs., lOyVo oz.)

Liquids (10 lbs., i lyVo oz.)

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 42.09 fl ^ (1,245.0 cc.)

Specific gravity 1028.6

Urea 710.00 grains, 46.065 grammes.

Nitrogen in urea 331-33 " 21.497

Uric acid 0.32 " 0.02 1

Phosphoric acid 84.95 " 5- 5^4

Sulphuric acid 73-39 " 4755

Chloride of sodium 96.00 " 6.220

This specimen of urine presented rather a faint cloudy sediment which
contained a large number of octahedra of the oxalate of lime.

EXCRETION OF NITROGEN 399

FECES

Quantity 4-8o oz. av. 136.0 grammes.

Nitrogen 25.77 grains, 1.670

Nitrogen in urea and feces combined. . 357-io " 22.167

Nitrogen of urea and feces per 100 parts of nitrogen of food . 235.63 parts.

Uric acid per 100 parts of urea 0.045 "

r Weight (naked) 1 16.5 lbs. (52 k. 838 grammes.)

Temperature under the tongue 95.3° (35-3° C.)

10.40P.M. \ p^i^^t; 98.

(^ Respirations 20.

NOVEMBER 22, SECOND DAY

The following is a summary of the twenty-four hours
of Xovember 22:

12 00 to 4 58 A. M. 4 h. and 58 m. rest, continued from November
21, before starting, making, during the night of
the 2ist and 22d, 6 h. and 25^^ m.
4 58 to 6 58 " 2 h. walking 8f miles, with i stop of 6 m. for defe-
cation.
10 m. rest, sitting on the track.
25 m. walking i-f- miles.

1 h. and 32 m. rest (breakfast).

2 h. and 7 m. walking 9* miles, with 2 stops for
urination, averaging 32 sec. each.

15 m. rest, sitting on the track.

2 h. and 14 m. walking 10 miles, with 2 m. rest
and 2 stops for urination, averaging 29 sec. each.

14 m. rest, sitting on the track.

2 h. and 10 m. walking 10 miles, with i stop for
urination, of 25 sec.
4 5 to 10 24 " 6 h. 19 m. Stopped for sleep but dozed only.

Ate supper before starting again.
10 24 to I2,less49sec. Walking 8 miles in i h. 36 m. less 49 sec. on his
walk of 112 miles in 24 h. and continued walk-
ing into November 23.

During the 24 hours of November 22, Weston walked 48 miles in
10 h. and 32 m., including 6 m. for defecation and 2 m. 27 sec. for urina-
tion. Deducting the time for defecation and urination, his walking-time
was 10 h. 23 m. and 33 sec, and he averaged about 4.62 miles per hour.
He had 39 minutes' rest, sitting on the track, and 12 h. and 49 m. for
breakfast, dinner, supper and sleep. He urinated 5 times on the track.
When he stopped at 4.05 p. M. he was undressed, wrapped in a long red-
fiannel gown and a blanket, carried to a vehicle and driven about five
blocks to a private house to sleep. He says that he did not sleep, but
dozed and got no rest. About 9 30 P. M. he was brought back to the rink
in the way he was taken out, ate supper and began at 10.24 P.M. his
first attempt to walk one hundred and twelve miles in twenty-four con-
secutive hours. He slept, during the twenty-four hours, 4 hours and 28
minutes.

6 58

to

7 8 "

7 8

to

7 33 "

7 33

to

9 5 "

9 5

to

II 12 "

II 12

to

II 27 "

II 27

to

I 41 P. M,

I 41

to

I 55 "

I 55

to

4 5 "

400 EXCRETION OF NITROGEN

Walkinj^ 48 miles. . 10 h. 23 m. 33 sec.

Defecation 6 "

Urination 2 " 27 "

Rest on tlie track.. 39 "

Rest off the track.. 12 " 49 "

22 h. 119 m. 60 sec. = 24 hours.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Roast beef 4.00 61.25

Chicken 2.25 34.45

Eggs 8.28 68.82

Milk 5.66 16.34

Bread 10.50 49.61

Potatoes 2.00 2.89

Butter 0.50 1.40

Sugar 1.75 00.00

Coffee 57.82 27.83

Tea 38.08 3.33

Lemonade 34-84 00.00

Salt 0.08 00.00

Pepper 0.05 00.00

165.81 265.92
(4,700.13 grammes.) (17,229 grammes.)

Total ingesta (10 lbs., Stoo oz-)

Liquids (8 lbs., S^%% oz.)

Analyses of Excretions of Twenty-four Hours

Quantity 33-50 fl | (99i-0 cc.)

Specific gravity 1030.0.

Urea 702.86 grains, 45.540 grammes.

Nitrogen in urea 328.00 " 21.252

Uric acid 0.14 " 0.009

Phosphoric acid 72.14 " 4-674

Sulphuric acid 56.90 " 3.687

Chloride of sodium 91.68 " 5.940

This specimen of urine presented rather a faint, cloudy sediment,
which contained a large number of octahedra of the oxalate of lime.

FECES

Quantity 7.94 oz. av. 225.0 grammes.

Nitrogen 42-64 grains, 2.763

Nitrogen in urea and feces combined. . 370.64 " 24.015 "

Nitrogen of urea and feces per 100 parts of nitrogen of food. 139.39 parts.
Uric acid per 100 parts of urea 0.020

lO p. M.

EXCRETION OF NITROGEN 401

r Weight (naked) 1 16.25 lbs. (52 k. 724 grammes.)

j Temperature under the tongue 94-8° (34.9° C.)

1 Pulse 93.

1^ Respirations 23.

NOVEMBER 23, THIRD DAY

The following is a summary of the twenty-four hours
of November 23:

12 00 to 6 6 a. M. 6 h. and 6 m. walking 27^ miles, with one stop of
4 m. 30 sec. for rest, and 4 stops for urination,
averaging 30^ sec. each.
8 minutes' rest, sitting on the track.
M. 7 h. and 17 m. walking 33 miles, with 4 stops for
urination, averaging 31^ sec. each.

6 minutes' rest, sitting on the track.
47 m. walking 3f miles, with one stop of 34 sec.

for urination.

7 minutes' rest, sitting on the track.
34 m. walking 2J miles.
27 minutes' rest, sitting on the track.
I h. 14 m. walking 5J miles, including 2 stops for

urination, averaging 2yl sec. each.
30 minutes' rest, sitting on the track.
30 m. walking 2 miles, with one stop of 58 sec.

for urination.

1 h. and 3 m. rest in his room (supper).

2 h. and 22 m. walking 11 miles, with one stop of
30 sec. for urination.

10 minutes' rest, sitting on the track.

I h. and 31 m. walking 7 miles, with one stop of

43 sec. for urination.
I h. and 8 m. rest, continued into November 24.

During the 24 hours of November 23, Weston walked 92 miles in
20 h. and 21 m., including 4 m. 30 sec. rest, and 7 m. 47 sec. for urina-
tion. His walking-time was 20 h. 8 m. and 43 sec. and he averaged a
fraction more than 4J miles per hour. He had i h. 32 m. and 30 sec.
rest, sitting on the track, and 2 h. and 11 m. rest in his room. Before 12,
midnight, November 22, he had walked 8 miles in i h. 35 m. and 11 sec,
making 100 miles in 24 h. and 28 m. His last rest of i h. and 8 m. was
continued into November 24 i h. and 33 m. He urinated on the track
14 times.

During the early part of the day, Weston seemed cheerful and con-
fident, but after walking about sixty miles, he complained of drowsiness
and found it absolutely impossible to make the time necessary to accom-
plish his hundred and twelve miles in twenty-four consecutive hours. He
stated that he was not fatigued, but suffered only from want of sleep. He
was not much depressed at his first failure, as he intended to make a sec-
ond trial of the hundred-and-twelve-mile walk.

He began, 10.24 P- M-> November 22, his first attempt to make 112
miles in 24 consecutive hours. He failed on account of want of sleep.

6 6

to

614 "

614

to

I 31 p.

I 31
I 37

to
to

1 37 "

2 24 "

2 24
231

3 5

332

to
to
to

to

2 31 "

3 5 "
3 32 "
446 "

446
516

to
to

516 "
5 46 "

546
649

to
to

649 "
9 II "

9 II
921

to
to

921 "

10 52 "

0 =;2

to

I 2 00 M.

40 2

EXCRETION OF NITROGEN

not having slept well the six hours before the attempt. He had no

passage from his bowels during these 24 hours. He slept, during the
24 hours, 30 minutes.

Walking 92 miles 20 h. 8 m. 43 sec.

Urination . . . .* 7 " 47 "

Rest on the track i " 32 " 30 "

Rest off the track 2 " 11"

23 h. 58 m. 1 20 sec. = 24 hours.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Beef-essence 22.26 84.73

Eggs 8.28 68.82

Milk 6.18 17.84

Bread 1.50 709

Oatmeal-gruel 6.78 2.55

Butter 0.50 1.40

Sugar 2.00 00.00

Coffee 95.95 46.18

Lemonade 27.56 00.00

Salt 0.08 00.00

Pepper 0.05 00.00

171. 14 228.61

(4,851.22 grammes.) (14.812 grammes.)

Total ingesta (10 lbs., i lyVo oz.)

Liquids (9 lbs., I4tVo oz-)

Analyses of Excretions of Twenty-four Hours

Quantity 40.56 fl 3 (1,200.0 cc.)

Specific gravity 1032 . 5.

Urea 851 .95 grains, 55.200 grammes.

Nitrogen in urea 397-58 " 25.760

Uric acid 4. 74 " o. 307

Phosphoric acid 102.25 " 6.625

Sulphuric acid 63.71 " 4.128

Chloride of sodium 44.45 " 2.880

This specimen presented a whitish, flocculent and rather copious sedi-
ment which contained a large number of octahedra of the oxalate of lime.

NO FECES PASSED

Nitrogen of urea (no feces) per 100 parts of nitrogen of food 173.91 parts.
Uric acid per 100 parts of urea 0.566 "

EXCRETION OF NITROGEN 403

f Weight inaccurately taken

J Temperature under the tongue 96.6' (35.9' C.)

11.15P. M. 1 Pulse (76 at 5 P. M.) 109.

Respirations 22 .

I

NOVEMBER 24, FOURTH DAY

The following is a summary of the twenty-four hours
of November 24:

12 00 to I 33 A. M. I h. 33 m, rest in room, continued from November
23, making in all, 2 h. 41 m. rest for the night
of November 23 and 24.
I 33 to 412 " 2 h. 39 m. walking 10 miles, with 3 m. stop for
defecation and 30 sec. for urination.
5 h. and 47 m. rest in room.

4 h. 59 m. walking 23!^ miles, with 3 stops for uri-
nation, averaging 30I sec. each.

5 minutes' rest, sitting on the track.
3 h. and 7 m. walking I4f miles, with 2 stops for

urination, averaging 42^ sec. each.
3 minutes' rest, sitting on the track.

16 m. walking i4 miles, with 30 sec. for urination.
10 minutes' rest, sitting on the track.
12 m. walking i mile.
12 minutes' rest in his room.

7 m. walking f of a mile.
56 minutes' rest in his room.

10 m. walking f of a mile, with 40 sec. for urina-
tion.

5 minutes' rest, sitting on the track.
33 m. walking 24- miles.

8 minutes' rest, sitting on the track.
19 m. walking li miles.
10 minutes' rest, sitting on the track.

17 m. walking i mile, with 50 sec. for urination.
33 minutes' rest in room.

9 m. walking f of a mile.

I h. and 30 m. rest in room, continued into Novem-
ber 25.

During the 24 hours of November 24. Weston walked 57 miles in 1 2
h. and 48 m., including 3 m. for defecation, and 5 m. and 26 sec. for uri-
nation. His walking-time was 12 h. 39 m. and 34 sec, averaging almost
exactly 4^ miles per hour. He had 41 m. rest, sitting on the track, and 10
h. and 31 m. rest in his room. He urinated on the track 10 times. His
last rest, i h. and 30 m., was continued into November 25, for 9 h. 56 m.,
making, during the night of November 24 and 25, 11 h. 26 m. rest.

He began, at 10.13 A. M., his second attempt to walk 112 miles in 24
consecutive hours. At 6.51 p.m. he became very dizzy. This increased
so that he staggered and could hardly see the track. After 6 rests and 6
attempts to continue his walk, he was forced to abandon the attempt at
10.30 P. M. He was excessively depressed at his failure, as it was then
impossible for him to accomplish the four hundred miles in five days. He

4 12

to

9 59 "

9 59

to

2 58 P. M,

258

to

3 3 "

3 3

to

6 10 "

6 10

to

613 "

613

to

6 29 "

6 29

to

639 "

639

to

651 "

651

to

703 "

703

to

7 10 "

7 10

to

806 "

806

to

8 16 "

8 16

to

821 "

821

to

854 "

854

to

9 2 "

9 2

to

921

9 21

to

931 "

931

to

948 "

948

to

10 21

10 21

to

10 30 "

10 30

to

12 00 M.

404 EXCRETION OF NITROGEN

took a little food, lay down and went to sleep about midnight. He slept
during this twenty-four hours, i hour ; but his sleep was continued into
the next day.

Walking 57 miles 12 h. 39 m. 34 sec.

Defecation 3 "

Urination 5 " 26 "

Rest on the track ... 41 "

Rest off the track 10" 31 "

22 h. 119 m. 60 sec. = 24 hours.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Roast beef 1.62 24,81

Beef-essence 10.33 39-32

Milk 8,75 25.27

Bread 6.62 31.28

Oatmeal-gruel 7-92 2 . 92

Sugar 3.62 00.00

Coffee 38.38 18.47

Tea 30.06 2.63

Lemonade 41.60 00.00

§alt 0.08 00.00

Pepper 0.05 00 . 00

Bicarbonate of potash. 0.04 00.00

149.07 144-70

(4,225.61 grammes.) (9.376 grammes.)

Total ingesta (9 lbs., $^1-^ oz.)

Liquids (8 lbs., g^^-^ oz.)

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 32.52 f^| (965.0 cc.)

Specific gravity 1029. 6.

Urea 688.98 grains, 44.641 grammes.

Nitrogen in urea 321.52 " 20.832

Uric acid 9.21 " 0.597

Phosphoric acid 66.30 " 4.296

Sulphuric acid 32.66 " 2. 116

Chloride of sodium 28.78 " 1.865

This urine presented a faint deposit like mucus which contained a
moderate number of octahedra of the o.xalate of lime with a few granules
of amorphous urates.

FECES

Quantity 5.030Z. av. 142.5 grammes.

Nitrogen 21.01 grains, 1.750

Nitrogen in urea and feces combined. 348.53 " 22.582
Nitrogen of urea and feces per 100 parts of nitrogen of food. 240. 86 parts.
Uric acid per 100 parts of urea i • 33^

EXCRETION OF NITROGEN 405

f Weight (naked) 114 lbs. (51 k. 704 grammes.)

I Temperature under the tongue 96-6" (35.9' C.)

10.40 P.M. \ p^j^^i^ 68

Respirations 18.

NOVEMBER 2=,, FIFTH DAY

The following is a summary of the twenty-four hours
of November 25:

12 00 to 9 56 A. M. 9 h. and 56 m. rest before starting, with i h. 30 m.
of November 24, make 1 1 h. 26 m. rest for the
night of November 24 and 25.
9 56 to 10 1 1 " 15 m. walking i mile.

10 II to 10 16 " 5 minutes' rest in room.

10 16 to 10 58 " 42 m. walking 3 miles, with i m. for urination,

10 58 to II 21 " 23 minutes' rest, sitting on the track.

11 21 to II 52 " 31 m. walking 2I miles.

11 52 to 12 42 P. M. 50 minutes' rest in room.

12 42 to II " 19 m. walking if mile, with 30 sec. for urina-

tion.

1 I to 2 39 " I hour 38 minutes' rest in room.

2 39 to 419 " I h. 40 m. walking 7 miles, with 25 sec. for urina-

tion.
4 19 to 4 34 " 15 minutes' rest in room.
4 34 to 619 " I h. and 45 m. walking 8 miles, with 2 stops for

urination, averaging 29^^ sec. each.

6 19 to 7 43 " I hour and 24 minutes' rest in room.

7 43 to 9 32 " I h. and 49 m. walking 9 miles, with 40 sec. for

urination.
9 32 to 9 50 " 18 minutes' rest, sitting on the track.
9 50 to II 31 " I h. and 41 m. walking 7 miles, with 2 stops for

urination, averaging 25 sec. each.
II 31 to II 41 " 10 minutes' rest, sitting on the track.

11 41 to 12 00 M. 19 m. walking 1^ miles.

During the twenty-four hours of November 25, Weston walked 40^
miles in 9 h. and i m., including 4 m. and 24 sec. for urination. His
walking-time was 8 h. 56 m. and 36 sec, averaging a fraction more than
4j miles per hour. He had 51 minutes' rest sitting on the track, and 14
h. and 8 m. rest in his room. He urinated on the track 7 times. After

12 M., he was in remarkably fine condition. He made several rounds in
less than i minute, one round in 54 sec, on his thirtieth mile, which was
done in 8 m. 32 sec. He walked about i mile from 12 to 12.15 A.M.,
November 26. At the conclusion of his walk he was in the best of
health and spirits. He slept, during the twenty-four hours, 9 hours
and 26 minutes.

Walking 4o| miles ... 8 h. 56 m. 36 sec.

Urination 4 " 24 "

Rest on the track 51 "

Rest in his room 14 " 8 "

22 h. 119 m. 60 sec. = 24 hours.

4o6

EXCRETION OF NITROGEN

TOTAL MILES WALKED

Nov. 21 80 miles.

" 22 48

" 23 92 "

" 24 57 "

" 25 40J "

317^ miles.

In going thirty-two times to his room, Weston walked, in addition to
the above, 0.883 of a mile. From midnight, November 25, to 12.15 A. M.,
November 26, he walked i| miles, to complete his five days. This, with
the few feet to the urinal, makes about 320 miles in five consecutive days.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av.

Roast beef 3 . 00

Chicken n .00

Beef-essence 9 54

Eggs 4-14

Milk 9.78

Bread 9.00

Potatoes 4.00

Oatmeal-gruel 3 • 39

Butter 1 .25

Sugar 2.37

Tomatoes 3.12

Coffee 27.27

Tea 40. 08

Lemonade 52.00

Water 5.00

Salt 0.08

Pepper 0.05

Nitrogen, in grains.

45-94
168.44

36.31
34.41
28.24
42.52

5-77
1.28

3-50

00. GO
00.00
13.12

3.51
00.00
00.00
00.00
00.00

185.07 383.04

(5,246.09 grammes.) (24.818 grammes.)

Total ingesta di lbs., 9y^ oz.)

Liquids (9 lbs., 7y|o oz.)

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 43.60 fl§ (1,290.0 cc.)

Specific gravity 1022.6.

Urea 657 .02 grains, 42 . 570 grammes.

Nitrogen in urea 306.61 " 19.866

Uric acid o. 57 " 0.037

Phosphoric acid 57-49 " 3-725

Sulphuric acid 40 . 84 " 2 . 646

Chloride of sodium 64.50 " 4.179

This urine presented a whitish grumous sediment, rather copious,
which contained a few octahedra of the oxalate of lime with a few gran-
ules of amorphous phosphates.

EXCRETION OF NITROGEN 407

FECES

Quantity 4.87 oz. av. 138.0 grammes.

Nitrogen 26. 16 grains, i .695

Nitrogen in urea and feces combined . 332.77 " 21.561
Nitrogen of urea and feces per 100 parts of nitrogen of food. 84. 27 parts.
Uric acid per 100 parts of urea 0.087 "

1 Weight (naked) 1 15-75 lbs. (52 k. 497 grammes.)

1.30 A. M. I Temperature under the tongue 97.9° (36.6° C.)

Nov. 26. "' Pulse 80.

[ Respirations 20 .

THIRD PERIOD, FIVE DAYS AFTER THE WALK

Notwithstanding the muscular and nervous strain to
which Weston had subjected himself for the past five days,
culminating on the fourth day in complete prostration of
the nervous system, he sat up, talked and joked with his
friends until 1.40 a.m., November 26, then went to bed
and slept well until 10 a. m. He then got up, " feeling
splendid," wakening his attendants, who were almost ex-
hausted by the five days' labor and watching, and called
for his breakfast, which he ate at 11.45, ■^'^ith excellent
appetite. For the succeeding five days he felt as well as
ever. During these five days he did absolutely nothing
but eat, sleep and amuse himself, attending to no business.
He took no exercise, walking only about two miles a day,
though he said he felt as if he could walk one hundred miles
any day without dif^culty. The history of this period
closed our investigations.

NOVEMBER 26. FIRST DAY

Weston slept well. He took breakfast at 11.45 a.m.
and dinner at 6.45 p. m. He smoked six cigars during the
day. He walked two miles. He slept, during the twenty-
four hours, eight hours and twenty minutes.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Turkey 7 50 114.84

Chicken 5.12 78.40

Fish 3.50 53.59

Eggs 4.14 3441

Milk 2.06 5.95

Custard 3.25 18.20

Ice-cream 3 -5° 19.60

Bread 7.75 36.62

4oS

EXCRETION OF NITROGEN

Oz. Av.

Potatoes 5 . oo

Butter 1 .88

Sugar 0.88

Cauliflower 3.00

Cranberries 5 .00

Celery i.oo

Lettuce 1.25

Grapes i . 00

Apples 5.00

Coffee 24.24

Lemonade 14.68

Water 30.00

Salt 0.15

Pepper 0.05

129.95

Nitrogen, in grains.
7.22
5.26
00.00
00.00
00.00
00.00
00.00
00.00
00.00
I I .56
00.00
00.00
00.00
00.00

385.65

(3,683.63 grammes.) (24.987 grammes.)

Total ingesta (8 lbs., lyV^ oz.)

Liquids (2 lbs., I4tV% oz-)

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 31 • 59 A 3 (937-5 cc)

Specific gravity 1025.8.

Urea 593—3 grains, 38 . 437 grammes.

Nitrogen in urea 276.84 " 17-937

Uric acid 0.48 " 0.031

Phosphoric acid 29.06 " 1.883

Sulphuric acid 49-53 " 3-209

Chloride of sodium 66.41 " 4 -303

This urine presented a rather heavy, whitish sediment in considerable
quantity which contained granules of the amorphous urates with a very
few octahedra of the oxalate of lime.

Quantity 3 . 5 1 oz. av. 99. 5 grammes.

Nitrogen 18.86 grains, 1.222

Nitrogen in urea and feces combined. . 295.70 " 19. 159 "
Nitrogen of urea and feces per 100 parts of nitrogen of food. 76.68 parts.
Uric acid per 100 parts of urea 0.081 "

r Weight (naked) 118 lbs. (53 k. 518 grammes.)

12.10 A. M. ) Temperature under the tongue 98.6° (37° C.)

Nov. 27. j Pulse 76 .

[ Respirations 22 .

NOVEMBER 2J, SECOND DAY

Weston slept well. He took breakfast at 10 a. m.; din-
ner at 2 p. M.; and supper at 6.45 p. m. He smoked seven
cigars during the day. He walked about two miles. He
slept, during the twenty-four hours, eight hours and fifteen
minutes.

EXCRETION OF NITROGEN 409

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Beefsteak 5.00 76.56

Roast beef 2.50 38.28

Turkey 9.00 137.81

Head-cheese 1.50 14.70

Eggs 4.14 34.41

Milk 5.14 14.87

Bread 16.15 76. 31

Cheese 1.13 20.28

Potatoes 10.25 14.82

Oysters 3-90 36.34

Ice-cream 2.88 16.13

Butter 2.75 7.70

Sugar 1.56 00.00

Tomatoes 5.25 00.00

Cranberries 4.50 00.00

Preserves 4-75 00.00

Catsup 0.42 00.00

Coffee ^9.19 9.23

Tea 19.04 1.66

Molasses-and-water. . . 21.45 00.00

Water 40 . 00 00 . 00

Salt 0.05 00,00

Pepper 0.06 00.00

180.61 499.10

(5,119.66 grammes.) (32.338 grammes.)

Total ingesta (11 lbs., 4yVo o^.)

Liquids (6 lbs., S-^^ oz.)

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 46.i4fl3 (1,365.0 cc.)

Specific gravity 1024.4.

Urea 716.29 grains, 46.410 grammes.

Nitrogen in urea 334 . 27

Uric acid 0.52

Phosphoric acid 46 . 93

Sulphuric acid 46.07

Chloride of sodium 1 70 . 64

21.658
0.034
3.041
2.985

II .056

This urine presented a slight sediment of a whitish appearance which
contained a few octahedra of the oxalate of lime and a few groups of small
crystals of uric acid.

FECES

Quantity 4.570Z. av. 129.5 grammes.

Nitrogen 24. 54 grains, i . 590

Nitrogen in urea and feces combined. 358.81 " 23.248 "
Nitrogen of urea and feces per 100 parts of nitrogen of food. 71.81 parts.
Uric acid per 100 parts of urea 0.072

27

4IO EXCRETION OF NITROGEN

II p. M.

Weight (naked) 120.25 lbs. (54 k. 539 grammes.)

Temperature under the tongue 98.4° (36.9° C.)

Pulse 73-

Respirations 22.

NOVEMBER 28, THIRD DAY

Weston slept well. He took breakfast at 8.50 a.m.;
dinner at 4.15 r. m.; and supper at 7.45 p. m. He smoked
five cigars during the day. He walked about two miles.
He slei^t, during the twenty-four hours, eight hours and
fifty minutes.
Weights and Analyses of Food and Drink for the 24 Hours

Oz. Av. Nitrogen, in grains.

Beefsteak 9.37 143-48

Oysters 5.62 53.37

Eggs 4-14 34-4I

Milk 9.27 26.76

Cream-cakes 3.37 18.97

Bread 11.62 54.8o

Cheese 1.25 22.53

Potatoes 11.00 15.88

Butter 2.75 7.70

Sugar 2.78 00.00

Tomatoes 3.75 00.00

Sweet pickles 2.18 00.00

Apples 3.12 00.00

Grapes 2.75 00.00

Coffee 32.32 15.53

Tea 16.03 1.40

Salt 0.06 00.00

Pepper 0.06 00.00

Vinegar 0.25 00.00

121.69 394-83

(3,449.49 grammes.) (25 . 582 grammes.)

Total ingesta (7 lbs., gf-^ oz.)

Liquids (3 lbs., g^y^ oz.)

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 84.18 fl| (2,490.0 cc.)

Specific gravity 1019.7.

Urea 768.61 grains, 49.800 grammes.

Nitrogen in urea 358 . 68 " 23 . 240 "

Uric acid 0.31 " 0.020 "

Phosphoric acid 105.68 " 6.847

Sulphuric acid 53-57 " 3-471

Chloride of sodium 622.58 " 40.338

This urine presented a slight sediment of a whitish appearance which
contained a few octahedra of the oxalate of lime and a few groups of
small crystals of uric acid.

EXCRETION OF NITROGEN 411

FECES

Quantity 9. 53 oz. av. 270.0 grammes.

Nitrogen 51. 19 grains, 3.316

Nitrogen in urea and feces combined. 409.87 " 26.556 "

Nitrogen in urea and feces per 100 parts of nitrogen of food. 103.81 parts.
Uric acid per 100 parts of urea 0.040 "

I Weight (naked) 120.25 lbs. (54 k. 539 grammes.)

I Temperature under tlie tongue.. ..... 99.3° (37.4° C.)

■ -5 ■ ■ I Pulse 70 .

l^ Respirations 22 .

NOVEMBER 2g, FOURTH DAY

Weston slept well. He took breakfast at 9.35 a.m.;
dinner at 2 p. m.; supper at 6.30 p. m.; and a second supper
(which weighed 3 lbs., 6.75 oz. av.) at 11. 15 p.m. He
smoked five cigars during the day. He walked about two
miles. He slept, during the twenty-four hours, seven
hours and thirty-five minutes.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Beefsteak 4.25 65.08

Roast beef ,. 2.75 42.11

Chicken 15.00 229.69

Eggs 4.14 34.41

Milk 6.25 18.05

Bread 18.63 88.03

Potatoes 13-50 20.59

Cheese i .00 18.03

Rice-pudding 14.75 77-15

Butter 5.12 14-33

Sugar 2.12 00 . 00

Tomatoes 7.38 00.00

Tomato-soup 8.00 00.00

Celery i.oo 00.00

Figs 2.37 9.54

Apples 7.00 00.00

Coffee 48 . 48 23 . 30

Tea ^6.03 1.40

Water 10.00 00.00

Salt 0.16 00.00

Pepper 0.08 00.00

188.01 641.71

(5,329.43 grammes.) (41 . 578 grammes.)

Total ingesta (11 lbs., 12-^^-0 oz.)

Liquids ( 5 lbs., 8^^^ oz.)

412 EXCRETION OF NITROGEN

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 60.38 fl§ (1,786.000.)

Specific gravity 1022 . 5.

Urea 744-3- grains, 48.226 grammes.

Nitrogen in urea 347-35 " 22 . 505

Uric acid 2.51 " 0.163

Phosphoric acid 50 - 76 " 3 - 289

Sulphuric acid 48-73 " 3-157

Chloride of sodium 297.70 " 19.288

This urine presented hardly any sediment. The microscopical exami-
nation was entirely negative.

FECES

Quantity 6.61 oz. av. 187.5 grammes.

Nitrogen 35.54 grains, 2.303

Nitrogen in urea and feces combined. 382.89 " 24.808 "
Nitrogen of urea and feces per 100 parts of nitrogen of food. 59.67 parts.
Uric acid per 100 parts of urea 0-337 "

I Weight* (naked) 123.5 lbs. (56 k. 13 grammes.)

12.20 A.M. I Temperature under the tongue 98.8° (37. 1° C.)

Nov. 30. I Pulse 78 .

1^ Respirations 24.

NOVEMBER 3O, FIFTH DAY

Weston slept well. He took breakfast at 9.15 a. m.;
dinner at 1.45 p. m.; and supper at 6.15 p. m. He smoked
during the day, six cigars. He walked about three miles.
He had a headache all the evening. He slept, during the
twenty-foiu" hours, seven hours and forty-five minutes.
The records were closed at midnight.

Weights and Analyses of Food and Drink for the Twenty-
four Hours

Oz. Av. Nitrogen, in grains.

Beefsteak 1.88 28.79

Roast beef 3.37 51.60

Fish 3.00 45-94

Milk 5.66 16.34

Bread 21.00 99.22

Potatoes 5.94 8.58

Butter 4.12 11-54

Sugar 1.88 00.00

Tomatoes 3- 12 00.00

Tomato-soup 8.00 00.00

Figs 2.06 8.29

Preserved citron 2.25 00.00

Coffee 24.24 11.65

* This great increase in weight is accounted for by 3 lbs. 6.75 oz. of food
taken at 11. 15 P. M.

EXCRETION OF NITROGEN 413

Oz. Av. Nitrogen, in grains.

Tea 16.03 1.40

Salt 0.06 00.00

Pepper 0.06 00.00

102.67 283.35

(2,910.34 grammes.) (18.359 grammes.)

Total ingesta (6 lbs., 6^^ oz.)

Liquids (2 lbs., 1 5^^^ oz.)

Analyses of Excretions of Twenty-four Hours

URINE

Quantity 68.39 fl 3 (2,023.0 cc.)

Specific gravity 1022.6.

Urea .... 81 1 .48 grains, 52 . 598 grammes.

Nitrogen in urea 378.69 " 24.546

Uric acid 3- 3° " 0.214 "

Phosphoric acid 52.00 " 3.364 "

Sulphuric acid 47-20 " 3.058 *'

Chloride of sodium 404.65 " 26.218

This urine presented a cloudy sediment in moderate quantity which
contained a moderate number of octahedra of the oxalate of lime.

FECES

Quantity 7.41 oz. av. 210.0 grammes.

Nitrogen 39 . 80 grains, 2 . 579

Nitrogen in urea and feces combined. 418.49 " 27.125

Nitrogen of urea and feces per 100 parts of nitrogen of food. 147.69 parts.

Uric acid per 100 parts of urea 0.406 "

I Weight (naked) 120.75 lbs. (54 k. 765 grammes.)

J Temperature under the tongue 97.5° (36.4° C.)

^^^- I Pulse 76.

[ Respirations 24.

CONSOLIDATED TABLES

I propose to present, in a series of consolidated tables,
the complete history of the fifteen days, divided as before
into three periods of five days each, in the form in which
they will be made use of in Part II. in making the final
deductions. I present them in this form complete, so that
all or any part of them may serve as material for the use
of others. The cutaneous and pulmonary exhalations were
estimated by subtracting the weight of urine and feces from
the weight of ingesta; and to this result adding any loss
of weight, or subtracting from it any gain in the weight
of the body during the twenty-four hours.

The weights are given in pounds and ounces avoirdu-
pois and in grains troy. The equivalents in French weights
are given in parentheses:

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423

Table D. — Daily Averages for the Three Periods
(French weights and measures in parentheses)

First period — five days
before the walk.

Second period — five
days of the walk.

Third period — five
days after the walk.

Weight

Temperature

Pulse

Respiration

Sleep

Miles walked. . . .
Ingesta

Nitrogen of food.

Cutaneous and pul-
monary exhalation

Urine.
Quantity ,

Specific gravity. . . .
Urea

Nitrogen in urea. . .

Uric acid

Phosphoric acid . . .

Sulphuric acid. . . .

Chloride of sodium

Loss in 5 days —
21.8 oz. (593 gr.)

Average of 5 days-
gg" Fahr.
(37-2' C.)
78
22

8 h. 5 m.
8.2 miles
100.50 oz.
(2,848.82 gr.)
33946 grains
(21.994J

61.63 oz.
(1,690.91 gr.)

37.84 fl. oz.

(1,134.0 cc.)

1024.9

628.24 grains

(40.705)

293.18

(1S.729)

2.26

(0.127)

50.14
(3.262)

41-57
(2.693)

159-45
(10.331)

Loss in 5 days —

52.2 oz. (1,565 gr.)
Loss in 4 days —

83.2 oz. (2,358 gr.)
Average of 5 days —

96.3 Fahr,

(35.7° C.)

90
21

3 h. 17 m.
63.5 miles
171.47 oz.
(4,860.57 gr.)
234.76 grains
(13. 211)

138.41 oz.

(3,875.18 gr.)

Gain in 5 days —
80 oz. (2,268 gr.

Average of 5 days-
98.6 Fahr.
(37° C.)
74
23

8 h. 29 m.
2.2 miles
144.59 oz.
(4,098.62 gr.)
440.93 grains
(28.569)

62.82 oz.
(1,706.78 gr.)

38.46 fl. oz.

(1,138.0 cc.)

102S.7

722.16 grains

(46.S03)

337-OI

(21.841)

3.00

(0.194)

76.63

(4-965)

53.50

(3.666)

65.08

(4.217)

58.14 fl. oz.
(1,720.3 cc.)

1023.0

726.79 grains

(47.094)

339.17

(21.977)

1.42

(0.082)

56.89

(3-674)
49.02

(3.176)
312.40
(20.241)

Feces.
Quantity ....

Nitrogen .

4.08 oz.
(115-6)
21.91 grains
(1.421)

4.53 oz.
(128.3)
24.32 grains.
(1.576)

6.33 oz.

(179.3)
33.99 grains
(2.202)

Nitrogen in urea and
feces combined. . .

315.09 grains
(20.149)

361.52 grains
(23.217)

Nitrogen of ureaand
feces per 100 pts.
of nitrogen of food

92.82 parts.

153.99 parts

Uric acid per 100
pts. of urea

0.360 parts

0.415 parts

373.15 grains
(24.179)

84.63 parts

0.195 parts

424

EXCRETION OF NITROGEN

Table E. — Meteorological Ohservations, taken at the Cooper Union,
New York City, by Prof. Oran W. Morris

1870.

BAROMETER.

THERMOMETER

(Fahrenheit).

Degree of humidity.
Saturation repre-
sented by 100.

WIND.

MONTH

AND

Daily readings corrected
and reduced to 32° Fahr.

Self-registering.

'Z c

82.0
78.0
42.5

42.0

74-0

60.0

48.5

72.0

77.0

79-3

82.0
89.0

90 0

88.5

80.0

General
direction.

SKY AND

ATMOS-
PHERE.

DAY.

High-
est.

Lowest.

Mean.

46.0
47.0
42.0

36.0
43-0

50.0

48.0

50.0
44.0

49.0

50.0
58.0

58.0
62.0

46.0

Low-
est.

35-0
37-0
29.0

27.0

33-0

38.0
39-8

36.0
33-0

39-0

40.0
42.0

44.0
38.0

34-0

V

tn

c
a

II. 0
10. 0
13.0

9.0

10. 0

12.0
9.0

14.0
II. 0

10. 0

10. 0
16.0

14.0
24.0

12.0

A. M.

NW

W

S w

w

w

S w

NE

s w
w

w

NW

w

NW

s w

NW

p. M.

s w
w
w

w

s w

w

N E

w
w

s w

NW
NW

s w

NW
S E

Nov.

Q

in.

in.

in.

°

Wed'day

16

30 . 065

29.817

29.911

40.60

Clear.

Thursday

17

30.146

30.059

30.099

43-16

Lightcl'ds

Friday

18

29.931

29.857

29.895

61.36

Slight rain
and slight
snow 6. 1 5

P. M.

Saturday

19

29.907

29-735

29.827

56.66

Snow
squalls.
Clear eve.

Sunday

20

29.950

29.932

29.942

43.20

Clear A.M.

Cloudy

eve.

Monday

21
22

30.167

29-954

30.029

44.70

Cloudy.

Tuesday

30.174

29.623

29.913

73-70

Rain all
day. Gale
eve.

Wed'day

23
24

29.763

29-547

29.624

51-30

Lightcl'ds

Thursday

29.892

29.832

29.861

43-46

Flying
clouds.

Friday

25

30.044

29.745

29.879

48.83

Clear A.M.
Cl'dy and
rain 10.15

P. M.

Saturday

26
27

28

29-715

29-477

29.569

63.13

Rain A.M.
Lightcl'ds

Sunday

29.914

29 . 803

29.846

46.40

Clear. 2

meteors

eve.

Monday

30.067

30.054

30 . 060

48.90

Lightcl'ds

Tuesday

29
30

30.033

29.811

29-949

60.76

Lightcl'ds
Slight rain
evening.

Wed'day

30.277

30.181

30.221

46.43

Lightcl'ds
Clear eve.

The height of the cistern of the
tide water. A severe gale

barometer is considered to be 46 feet above
N. E., and very high tide, on the 22d.

EXCRETION OF NITROGEN 425

PART II

PHYSIOLOGICAL DEDUCTIONS FROM THE OBSERVATIONS
TAKEN BEFORE, DURING, AND AFTER THE WALK OF
317^ MILES IN FIVE CONSECUTIVE DAYS

The data obtained during the three periods, five days
before, five days during and five days after this walk, en-
able me to come to certain conclusions in regard to physi-
ological questions of interest, particularly the influence of
muscular exercise upon the elimination of nitrogen. In
regard to the influence of this excessive and prolonged
exertion upon the weight of the body, the temperature,
circulation, respiration, nervous system, etc., the informa-
tion is necessarily more incomplete and indefinite. I shall,
however, endeavor to make use of the facts that were noted;
although the main object was to study the relations of the
nitrogen.

The phenomena observed relate to the weight of the
body, temperature, pulse and respirations, in so far as
these conditions were modified by exercise and sleep.
Having taken daily the weights of the ingesta, the excre-
tions by the kidneys and intestines and the weight of the
body, it was possible to calculate the amount of exhalation
from the lungs and skin.

WEIGHT OF THE BODY

It is well known that by regulating the diet and exer-
cise, the weight may be modified within certain limits; and
the system of training employed by athletes is supposed
to develop to the highest degree the muscular power and
endurance. The principle in training is in brief to regulate
the exercise so that gradually the system is worked daily
as much as can be endured without exhaustion; and to
restrict the diet to rare, lean meats, stale bread and nitrog-
enous articles, eliminating fatty matters and reducing the
starchy matters to a minimum. By this process the weight
is reduced — for professional athletes out of training are gen-
erally over-weight — the muscles are hardened, nearly all
the fat disappears, and the power, and within limits the
endurance, are developed to a maximum. In the case of
AVeston no rigid system of training was adopted; but the

23

426 EXCRETION OF NITROGEN

changes in weight are interesting in view of the great
variations in his diet during the three periods and the dif-
ferences in the amount of exercise taken.

When the investigations were begun, at midnight, No-
vember 15, the weight was 120.5 l^s. (54 k. 655 grammes).
At the end of the five days it had been reduced to 119.:^
lbs. (54 k. 62 grammes). The hghtest weight during this
period was on the fourth day, when it was 118.5 lbs. (53.
k. 745 grammes). On the second day the weight increased
to 121.25 l^s. (55 kilos.).

First Period, Five Days before the Walk. — On
the first day, the weight being unchanged, Weston walked
fifteen miles; he took 122.99 oz. (3,492.17 grammes) of
food and drink, containing 361.22 grains (23.404 grammes)
of nitrogen. He discharged 44.20 oz. (1,303.08 grammes)
in the urine and feces, and 78.79 oz. (2,189.09 grammes)
by the lungs and skin. The weather was clear and dry,
the temperature ranging between 35° and 46° Fahr. As-
suming the usual quantity of food and drink for an ordi-
nary man to be about 90 oz. (2,542 grammes), containing
about 310 grains (20 grammes) of nitrogen,* rather an
excess was taken on this day. The cutaneous exhalation
was excessive. Allowing 20 oz. (567 grammes) for pul-
monary exhalation, which is fairly constant, the cutaneous
exhalation amounted to 58.70 oz. (1,658.27 grammes), the
normal amount being about 30 oz. (850 grammes). f

On the second day there was a diminution in the total
quantity of food and drink and in the quantity of nitrogen
(total food and drink, 105.43 oz. [2,987.92 grammes]*
nitrogen, 288.35 grains [18.682 grammes]), with an in-
crease in weight of 12 oz. (345 grammes), the urine and
feces being diminished about 0.5 oz. (15.13 grammes), and
the cutaneous exhalation about 29 oz. (834.12 grammes).
The weather was a little warmer, but cloudy and damp.
The only explanation I can offer for this increase in weight
is in the exercise, which was only five miles.

On the third day there was a loss in weight of 20 oz.
(567 grammes). On this day there was a further diminu-

* Flint, "Physiology of Man," New York, 1867, vol. ii., Alimentation,,
p. 124.

f /(/., 1866, vol. 1., Respiration, p. 447 ; and, Id., 1870, vol. iii.. Secretion,
p. 139-

EXCRETION OF NITROGEN 427

tion in the quantity of food and drink and in the nitrogen
(total food and drink, 86.56 oz. [2,453.67 grammes] ; nitro-
gen 272.27 grains [17.641 grammes]). The urine and
feces were increased by about 8.25 oz. (243.58 grammes),
and the cutaneous exhalation, 4.88 oz. (142.17 grammes).
The exercise was five miles, the same as on the second
day.

On the fourth day the weight was diminished 24 oz.
(687 grammes). The total quantity of food was about the
same as on the third day (86.19 oz. — 2,443.19 grammes).
The nitrogen was increased by about 63 grains (4.065
grammes). The urine and feces were diminished by about
15.5 oz. (455.03 grammes), and the cutaneous exhalation
was increased by about 19 oz. (549.55 grammes). The
exercise on this day was fifteen miles, wdiich, with the
diminished ingesta, will account for the loss in weight.

On the fifth day there was a gain in weight of about
II oz. (317 grammes). The total quantity of food and
drink w'as increased over the quantity on the fourth day
by about 15 oz. (429.44 grammes). The nitrogen was
increased by more than 105 grains (6.830 grammes). The
urine and feces were about the same as on the fourth day.
The cutaneous exhalation was diminished by 22.27 o^-
(680.02 grammes). The exercise on this day was only one
mile. The increase in w'eight is to be explained only by
the want of exercise and the large quantity of solid food
taken.

Second Period, Five Days of the Walk. — This
period presents the greatest interest as regards the influ-
ence of the diet and exercise upon the weight of the
body.

On the first day, walking eighty miles and sleeping but
one hour, the loss of weight was about 45 oz. (1,224.00
grammes). The quantity of food and drink was increased
over the quantity on the day before by about 85 oz. (2,409.-
75 grammes), the increase being chiefly in liquids. The
nitrogen was diminished by 289 grains (18,716 grammes).
The feces were but slightly increased. The urine was in-
creased by about 8 oz. (195 cc). The estimated cutaneous
exhalation was increased by 130 oz. (3,723.11 grammes),
a little more than two and a half times. The loss in weight
was undoubtedlv due in a ereat measure to the extraordi-

428 EXCRETION OF NITROGEN

nary amount of exercise. I shall endeavor to explain this
more fully when I compare the weights for the three
periods.

On the second day, walking forty-eight miles and
sleeping 4 hours and 28 minutes, there was a further loss
of 4 oz. (114 grammes). The quantity of food and drink
was diminished by about 21 oz. (582.25 grammes), but the
nitrogen was increased by about 114 grains (7.409
grammes). The feces were increased by a little more than
3 oz. (89 grammes). The urine was diminished by about
8.5 oz. (254 cc). The cutaneous exhalation was dimin-
ished by 54 oz. (1,521.38 grammes). The loss of weight
I shall endeavor to explain farther on.

On the third day, walking ninety-two miles and sleep-
ing but thirty minutes, the loss of weight was estimated
at 20 oz. (567 grammes). The weight was not accurately
taken on this day and was averaged.

On the fourth day, walking fifty-seven miles and sleep-
ing one hour, the weight was 36 oz. (1,020.00 grammes)
less than on the second day. (This represents the loss for
two days.) The food and drink were, for the third day,
about 5 oz. (151.09 grammes) more than for the second
day, and for the fourth day, about 22 oz. (625.61 grammes)
less than for the third day. On the third day the nitrogen
was diminished by about 37 grains (2.417 grammes). On
the fourth day the nitrogen was further diminished by 84
grains (5.436 grammes). There were no feces on the third
day, and the urine was increased by about 7 oz. (209 cc).
On the fourth day the feces were in about average quan-
tity. The urine was diminished about 8 oz. (235 cc). On
the third day the cutaneous exhalation w-as increased by
about 22 oz. (610.82 grammes). On the fourth day the
cutaneous exhalation was diminished by about 23 oz.
(636.67 grammes). I shall discuss the loss of weight in
connection with a comparison of the three periods.

On the fifth day, walking forty and a half miles and
sleeping 9 hours and 26 minutes, there was an increase in
weight of 28 oz. (793.00 grammes). The food and drink
were increased by 36 oz. (1,020.48 grammes). The nitro-
gen was increased by 239 grains (15.442 grammes), about
two and two-thirds times. The feces were diminished by
0.16 oz. (4.50 grammes), and the urine was increased by

EXCRETION OF NITROGEN 429

about 1 1 oz. (325 cc). The cutaneous exhalation was
diminished by about 19 oz. (546.61 grammes).

The loss of weight during this period of extraordinary
muscular exertion is an interesting question; and it will
be considered in connection with, not only the quantities
of food, drink, excretions and exhalations, but the quan-
tities of nitrogen introduced and discharged.

Third Period, Five Days after the Walk. — It is
to be remembered that this period was one of nearly abso-
lute repose after the exertion of the preceding five days,
with a daily average of eight and a half hours of sleep.

On the first day the w'eight increased by 36 oz. (1,021.00
grammes). The weight of food and drink was dinjinished
by about 55 oz. (1,662.46 grammes), but the quantity of
nitrogen was about the same as on the fifth day of the
second period. The feces w^ere diminished by 1.36 oz.
(38.50 grammes), and the urine, by about 12 oz. (352.50
cc). The cutaneous exhalation was diminished by nearly
50 oz. (1,394.50 grammes). The increase in weight was
probably due in greatest part to retention of liquids and
appropriation of nitrogenous matters to supply the mus-
cular waste that had been going on for the previous five
days. For the five days of the walk, for every 100 parts of
nitrogen of food there was a discharge of 174.81 parts in
the urine and feces. On this, the first day, the discharge
of nitrogen was in the proportion of 76.68 parts per 100
parts in the food.

On the second day there was a further gain in weight of
36 oz. (1,021.00 grammes), which brought the weight to
120.25 lbs. (54 k. 539 grammes), about the weight at the
beginning of the observations, which was 120.5 l^^s. (54 k.
655 grammes). The w-eight of food and drink was in-
creased by 50.66 oz. (1,436.03 grammes), and the nitrogen
was increased by about 113 grains (7.351 grammes). The
feces w-ere increased by about i oz. (28.35 grammes), and
the urine, by about 14.5 oz. (427.15 cc). The cutaneous
exhalation was increased by about 34 oz. (969.41 grammes).
This day was warm, clear and dry, the first day being rainy
and 5°'^to 8° Fahr. colder.

On the third day the weight was unchanged. The food
and drink were diminished by 59 oz. (1,670.17 grammes),
and the nitrogen, by about 104 grains (6.756 grammes).

430 EXCRETION OF NITROGEN

The feces were increased by 5 oz. (140.5 grammes), a little
more than doubled. The urine was increased by 38 oz.
(1,125 cc-)' nearly doubled. The cutaneous exhalation
was diminished by about 66.5 oz. (1,930.61 grammes),
more than three times. This day shows a working off
by the urine and feces of the unusual amount of food,
especially nitrogenous matter, taken on the previous day,
the weight remaining stationary.

On the fourth day the weight was increased by 52 oz.
(1,474.00 grammes). This great increase is explained by
the following circumstance: At 11. 15 p.m. Weston took
supper, the food and drink weighing 54.75 oz. (1,547.36
grammes). The weight of the body was taken at 11.55
p. M., about the usual hour. This was the only time when
anything was eaten after 7.45 p. m. This accident renders
it useless to discuss the question of weight on this day.
On this day the nitrogen of the food was largely increased,
amounting to 641.71 grains (41,578 grammes), the average
for an ordinary man being about 310 grains (20 grammes).

On the fifth day the weight was about the same as on
the third day, the increase being only 0.5 lb. (226
grammes). On this, the final day of the observations, the
weight was about the same as on the first day of the first
period, being increased only a quarter of a pound. The
food and drink were diminished by about 85 oz. (2,419.09
grammes), and the nitrogen, by about 358.5 grains (23,219
grammes). The feces were increased by about i oz. (22.5
grammes), and the urine, by 8 oz. (237 cc). The cuta-
neous exhalation was increased by about 1.68 oz. (37.87
grammes).

Causes of the Variations in Weight.* — In a meas-
ure, the variations in weight during the fifteen days may
be satisfactorily explained; but there are certain questions
involved that are as yet obscure. The explanation of the
variations during the walk and for the five days after is
much facilitated by a comparison of the ingress and egress
of nitrogen.

At the beginning of the investigations the weight was
120.5 lbs., which Weston thought was about normal. Dur-

* To avoid complicating the discussion of the causes of the variations in
weight, the English weights only will be used.

EXCRETION OF NITROGEN 431

ing the period of five days before the walk the variations
were not very great, the highest being 12 oz. above, and
the lowest, 32 oz. below. At the end of the fifth day the
weight was reduced by about 21 oz. On the first day, the
weight being unchanged, the exercise was fifteen miles.
The food was of the usual variety, but its quantity and
proportion of nitrogen were about 30 per cent, above the
average for an ordinary man. On the second day the di-
minished exercise, the food being less but still above the
normal average, will account for the increase in weight of
12 oz. On the third day the exercise was the same as on
the second day; but the food was reduced a little below
the normal average, which will account for 20 oz. loss of
weight. On the fourth day the food was still below the
average, being about the same as on the previous day; but
it contained a large proportion of nitrogenous matter, 20
per cent, more than on the third day. The exercise was
fifteen miles, which, with the diet, will account for 24 oz.
loss of weight. On the fifth day the food was increased
to a little above the average, and it contained a large quan-
tity of nitrogen, about 35 per cent, above the average.
This fact, with the absolute muscular repose and ten hours'
sleep as a preparation for the walk, will readily account
for 1 1 oz. increase in weight. During this period of five
days before the walk the average quantity of food and
drink was 100.5 oz., containing 339.46 grains of nitrogen,
the ordinary average being 90 oz., containing 310 grains
of nitrogen. The average discharge of nitrogen by the
urine and feces was 95.53 parts per 100 parts of the nitro-
gen of food, which is about normal. Thus it is evident
that the variations in weight during a period of five days
of ordinary life can be explained in accordance with gen-
erally accepted physiological principles.

In endeavoring to explain the variations in weight that
occurred during the walk, and for the succeeding five days,
the extraordinary muscular exertion introduces new ele-
ments to be considered. These have an important bearing
upon the subject of nutrition, disassimilation and " the
source of muscular power," about which so much has been
written within the last few years.

First: What tissue was consumed, the products being
thrown of¥, during the effort of walking 317? miles in five

432 EXCRETION OF NITROGEN

consecutive days? Was it the muscular substance? The
importance, as regards the processes of nutrition, of a defi-
nite answer to this question can hardly be overestimated.

The loss of weight was undoubtedly due in great meas-
ure to the excessive muscular exertion, but in part, also,
to change in diet.

The loss must have been either in liquids, fats or mus-
cular substance.

It is not probable that the loss was due in any great
degree to a diminution in the proportion of liquids, for
the excessive loss from the skin was supplied by liquids
taken into the stomach. It is not necessary to cite experi-
ments which show that loss by the skin, as it occurs in
hot-air or vapor-baths or in working for an hour or more
at a high temperature, is readily compensated by liquid
ingesta, as this fact is well settled in physiology.* A glance
at the daily tables of food and drink will show that during
the five days of the walk Weston took 8 lbs. 8 oz. to lo lbs.
II oz. of liquids.

If the loss was due to a consumption of non-nitroge-
nous matters, it would be chiefly of fat and would be rep-
resented by the carbonic acid of expiration. It is certain
that the non-nitrogenous constitutents of the body do not
contribute to the formation of the nitrogenous excremen-
titious matters.

If the loss was due to a consumption of the nitrogenous
constituents of the body, principally of the muscular tissue,
this loss, under the extraordinary muscular effort, would
be represented by the nitrogen of the excretions. It is
not probable that the nitrogenous constituents of the body
are in any considerable amount changed into non-nitrog-
enous matter and exhaled in the form of carbonic acid,
though this probably does occur to some extent.

The question then resolves itself to one of the relative
consumption and elimination of nitrogenous matters. The
following are the facts on this point, obsen^ed during the
five days of the walk:

During the five days of the walk f Weston consumed
in all, 1,173.80 grains (76.055 grammes) of nitrogen in his

* See my work on Physiology, New York, 1870, vol. iii., p. 140 et seq.
f I have reduced these calculations, on account of their great importance, to
grammes.

EXCRETION OF NITROGEN 433

food. During the same period he ehminated 1,807.60
grains (116.084 grammes) of nitrogen in the urine and
feces. This leaves 633.80 grains (40.030 grammes) of nitro-
gen, over and above the nitrogen of the food, which must
be attributed to the waste of his tissues, and probably al-
most exclusively to the waste of his muscular tissue. Ac-
cording to the best authorities, lean meat uncooked, or
muscular tissue, contains 3 per cent, of nitrogen.* The
loss of 633.80 grains (40.030 grammes) of nitrogen would
then represent a loss of 21,127.00 grains (1.334.33
grammes), or 3.018 lbs. of muscular tissue. The actual
loss of weight was 3.450 lbs. (1,565.00 grammes). This
allows about 0.43 lb. (230.67 grammes) loss unaccounted
for, which might be fat or water.

The correspondence of these figures of loss calculated
from the quantity of nitrogen eliminated with the actual
loss in weight leaves little room for doubt in regard to
the fact that the immense exertion during this period of
five days was attended with consumption of muscular sub-
stance. Those who have adopted the view that the mus-
cular system is like a steam-engine, consuming in its work
food as fuel and not its own substance, may say that this
is an extraordinary case, as it undoubtedly is; but the facts
developed by the foregoing observations prove, none the
less conclusively, that the muscular system may consume
its own substance by exercise, even when the individual
takes all the food required by his appetite. It can hardly
be, however, that the foregoing facts are not in accordance
with a general physiological law.

It will be interesting, now, to study the behavior of the
system after the walk, when there was almost absolute re-
pose and when the quantity of nitrogen taken with the
food was largely increased. The important question here
is the following:

In the return of the weight to the normal standard, did
the muscular tissue take up nitrogen to repair the excessive
waste engendered by the five days of exertion?

In two days after the walk the weight had increased to
within four ounces of the weight at the beginning of the
observ^ations, five days before the walk. It is not to be

* Payen, " Precis theorique et pratique des substances alimentaires," Paris,
1865, p. 48S.

434 EXCRETION OF NITROGEN

expected that this increase would be due entirely to appro-
priation of nitrogenous matter by the muscular system.
Reference to the tables of diet for these two days shows
that the food taken was about 155 oz. each day, the normal
average being assumed at 90 oz., an excess of a little more
than 70 per cent. The nitrogen taken was about 50 per
cent, in excess of the normal quantity. The tables also
show a large proportion of non-nitrogenous matter in the
food on those days. The exercise was only two miles daily.
Weston gained in weight 4.5 lbs. He retained in his sys-
tem a quantity of nitrogen equivalent to i.i lb. In view
of the muscular inactivity and the large proportion of Jion-
nitrogenous matter in the food, it is fair to assume that the
remaining 3.4 lbs. were due to accumulation of fat. This,
however, is a point incapable of positive demonstration.
Taking the entire period of five days after the walk, the
gain in weight was five pounds, which brought it to 4 oz.
above the weight at the beginning of the fifteen days. The
excess of the nitrogen of food over the nitrogen of the
urine and feces represented, for these five days, an accu-
mulation of 1.6 lb. of muscular substance. During this
time there was almost complete repose of the muscular
system. The daily quantity of food was about 61 per cent,
over the normal average, and the nitrogen, about 42 per
cent, over the average. The food contained, also, a large
proportion of non-nitrogenous matter.

These facts seem to indicate that after the effort in
walking 317I miles in five consecutive days, for five days
of muscular inactivity, the quantity of food being large
and containing a greater proportion of non-nitrogenous
matter than the food taken either before or during the
walk, the muscular system appropriated 1.6 lb. of nitroge-
nous matter, and the entire body accumulated about 3.4
lbs. of fat. It is well known that athletes, after a season
of severe training by exercise and nitrogenous diet, accu-
mulate fat very rapidly, when the muscles are allowed
repose and the diet is unrestricted.

TEMPERATURE, PULSE AND RESPIRATIONS

The temperature under the tongue for every day during
the three periods was carefully taken, as nearly as possible
at the same hour and under the same conditions. During

EXCRETION OF NITROGEN 435

the five days of the walk the temperature was taken after
the day's walk had been accomplished; and during the five
days before and the five days after the walk it was taken
generally between 10.45 ^- ^^- ^^*i midnight.

First Period, Five Days before the Walk. — The
temperatures for each day do not present any great range
of variation. The data here are useful chiefly as indicating
the normal average under ordinary conditions. The high-
est temperature was at the end of the first day. It was
then 99.7° Fahr. (37.6° C). The lowest temperature was
on the third day, when it was 98° Fahr. (36.7° C). On
the first day the quantity of food and drink and the pro-
portion of nitrogen were above the average by about 20
per cent. The exercise was fifteen miles. On the third
day the quantity of food and drink was a very little below
the average, and less nitrogen was taken than on any of the
five days. The exercise was five miles. On the fifth day
the temperature was within 0.2° Fahr. of the temperature
on the first day. On this day the quantity of food and drink
was slightly above the average, but the nitrogen of the
food was increased by 42 per cent. The exercise was only
one mile. On the first day the weather was clear, the high-
est temperature in the shade was 46° and the lowest, 35°
Fahr. On the fifth day it also was clear, and the highest
temperature was 43° and the lowest, 30° Fahr. On the
third day the meteorological record was, " slight rain and
slight snow 6.15 p. m.," highest temperature 42°. and low-
est 29° Fahr. On the fourth day, when the temperature
under the tongue was 99.1° Fahr. (37.3° C), the external
temperature was 36°, highest, and 2y°, lowest, "snow-
squalls, clear evening." On this day the total quantity of
food and drink was the same as on the third day, but the
nitrogen of the food was increased by about 23 per cent.
On the fourth day the exercise was fifteen miles. On the
second day, when the temperature under the tongue was
98.4° Fahr. (36.9° C), the nitrogen of the food was only
16.08 grains more than on the third day. The weather
was cloudy, the highest temperature, 47° and the lowest,
7^y° Fahr.

In the range of temperature during the five days of this
period, there does not seem to be any marked difference
due to the exercise. The variations apparently bear some

436 EXCRETION OF NITROGEN

relation to the quantity of nitrogenous food, the tempera-
ture being high when the nitrogen of the food is abundant
and low when the proportion is small. The temperature
w^as markedly higher on the clear days, without any defi-
nite relation to the external temperature.

The range of temperature for these five days was about
normal, 98° to 99.7° Fahr. (36.7° to 37.6° C). In my
work on physiology I have taken, as the standard tem-
perature under the tongue, 98° Fahr., subject to varia-
tions within the limits of health of about 0.5" below and
1.5° above.*

The average temperature for the first period of five
days before the walk, which I shall take as the standard
for comparison with the temperatures at the other periods,
is 99° Fahr. (37.2° C).

Second Period, Five Days of the Walk. — The
variations in temperature during this period are remark-
able, and are highly interesting from their possible physi-
ological relations. By reference to the meteorological
table (E.), it will be seen that the weather during this
period was generally cloudy, without much variation from
day to day in the thermometer. There does not appear to
be any constant relation, during this period, between the
temperature and the daily consumption of nitrogen.

On the first day, between 12.15 ^- M- ^^^ ^^-S-i P- M-
Weston walked eighty miles. His temperature was taken
eight minutes after he had completed the walk, and was
95.3° Fahr. (35.3° C), 4.3° less than the last temperature
taken before the walk was begun. This is a large reduc-
tion, greater than ever occurs under the ordinarv condi-
tions of health; and it can be attributed only to the ex-
traordinary muscular exertion during the day.

On the second day, between 4.58 a. m. and 4.5 p. m.,
Weston walked forty miles, when he stopped for 6 hours
and 19 minutes. At 10 p. m., about six hours after the
stop, the temperature was 94.8° Fahr. (34.9° C), a reduc-
tion from the temperature of the first day of 0.5°. Weston
did not sleep well, as he had hoped to do during the six
hours. At 10.24 p. M. he began his first effort to walk one
hundred and twelve miles in twenty-four consecutive hours.

* " Physiology of Man," New York, 1870, vol. iii., Nutrition, p. 396.

EXCRETION OF NITROGEN 437

I now think the further lowering in the temperature was
an indication of want of proper reaction after the walks he
had already accomplished. Had I appreciated the facts at
that time, I should have advised him to defer his attempt
to accomplish the hundred and twelve miles until a later
period. As it was, the attempt was a failure.

As on the first day the lowering in temperature is to
be attributed only to the excessive and prolonged muscu-
lar exertion.

On the third day, between midnight of the second day
and 10.52 p. M., Weston walked ninety-two miles. At 11. 15
p. M. the temperature was 96.6° Fahr. (35.9° C), 1.8°
higher than on the second day.

On the fourth day Weston walked fifty-seven miles be-
tween 1.33 A. M. and 10.30 P. M. The temperature, taken
at 10.40 P. M., was 96.6° Fahr. (35.9° C), the same as on
the third day. This was the day on which the walk was
interrupted by breaking down.

On the fifth day Weston walked forty and a half miles
between 9.56 a. m. and midnight. He continued walking
for fifteen minutes after midnight. He was in fine spirits
all day. During this twenty-four hours, for the first time,
he got sufficient refreshing sleep. He slept nine hours and
twenty-six minutes. The temperature, taken at 1.30 a. m.
of the next day, was 97.9° Fahr. (36.6° C); an increase
of 1.3° over the temperature of the day before.

It is difiicult to explain satisfactorily the elevation of
temperature by 1.8° on the third day, the day of the longest
walk, and the same temperature on the fourth day, when
Weston broke down completely. The temperature, how-
ever, on these days was still 2.4° below the average of the
five days before the walk, and 2° below the average of the
five days after the walk. The elevation in temperature
on the fifth day, by 1.3°, was probably on account of the
sleep of nine hours and twenty-six minutes.

The average temperature during this period was 96.3°
Fahr. (35.7° C); 2.7° below the average of five days be-
fore, and 2.3° below the average of five days after the
walk. The nearly uniform depression of temperature dur-
ing this period of excessive exertion shows pretty con-
clusively that severe and prolonged muscular exercise di-
minishes the heat of the body. It has been observed that

438 EXCRETION OF NITROGEN

during or immediately after moderate exercise, the heat
of the body is increased; and that the actual temperature
of the muscles is sensibly elevated;* but this is quite dif-
ferent from the great muscular and nervous strain to which
Weston subjected himself for five days. The fact of
diminution of temperature during this period remains,
therefore, without any explanation, except that it was
probably due to some unusual condition of the nervous
system.

Third Period, Five Days after the Walk. — Dur-
ing this period there was but little variation in the tem-
perature from day to day. On the first day the tempera-
ture was 98.6° Fahr. (37° C), 0.7° higher than on the
last day of the walk. This temperature was about normal.
On the second day the temperature was 98.4° Fahr. (36.9^
C); on the third day, 99.3° Fahr. (37.4° C); on the
fourth day, 98.8° Fahr. (37.1° C); and on the fifth day,
97.5° Fahr. (36.4° C). This range of temperature
was about normal, assuming, as I have done, that the
average is 98° Fahr., with a range of 0.5° below and 1.5°
above. The average temperature for the five days was
98.6° Fahr. (37° C), 0.4° less than "the average for the
five days before the walk and 2.3° more than the average
for the five days of the walk.

In studying the variations in temperature from day to
day during this period, I have not been able to find any
definite relation with the food or with the meteorological
record. The difference between the average during this
period and the average for the five days before the walk
is insignificant. It is interesting to note, however, that so
soon as the extraordinary muscular effort ceased, the tem-
perature returned to about the normal standard.

Pulse and Respirations. — During the first period
there was very little variation in either the pulse or respi-
rations. The extremes for the pulse were 93 and 71. The
pulse was 93 just before the walk; and this probably was
due to excitement incident to the occasion. At that time,
also, the respirations were 25. For the first three days
the respirations were 20, and on the fourth day, 23.

* For an account of different observations on this point, see my work on.
Physiology, New York, 1870, vol. iii., Nutrition, p. 413.

EXCRETION OF NITROGEN 439

During the five days of the walk the pulse ranged be-
tween 68 and 109. The pulse was 109 on the third day,
when the exercise was ninety-two miles. The range of
the respirations was between 18 and 23. On the fourth
day, after Weston had completely broken down in his walk,
the pulse was 68 and the respirations 18.

For the five after the walk the range of the pulse was
between 70 and 78, and the respirations were between
22 and 24.

The averages for the five days before the walk were,
for the pulse, 78, respirations 22; for the five days of the
walk, pulse 90, respirations 21; and for the five days after
the walk, pulse 74, respirations 23.

In the absence of sphygmographic records of the pulse,
there could be little learned from the observations on the
circulation. The variations in the respirations, also, con-
vey little information. It was impossible, however, to make
the records on these points more elaborate; and as it was
necessary to make all of the observations without sub-
jecting Weston to any considerable annoyance or loss of
time, experiments with the sphygmograph would have
been impracticable.

The records in regard to sleep, exercise, quantity of
food and drink and the composition of the food were made
to be used in connection with the question of the elimina-
tion of nitrogen, and will not, therefore, be discussed sepa-
rately. The cutaneous and pulmonary exhalations were
calculated from the weight of ingesta, urine and feces and
the variations in the weight of the body. As these were
not directly estimated they will not be discussed under
distinct heads.

VARIATIONS IN THE URINE DUE TO EXERCISE, STUDIED
IN CONNECTION WITH THE PROPORTION OF NITROGEN
IN THE FOOD

In discussing the variations in the urine during the
three periods into which the investigations were divided. I
shall take up first the quantity; then the urea, or the quan-
tity of nitrogen eliminated in the urea, in connection with
the nitrogen of the feces, and compare the total elimination
of nitrogen with the quantity introduced with the food;

440 EXCRETION OF NITROGEN

then the uric acid and its relations to the urea; and finally,
the inorganic salts and abnormal matters.

QUANTITY OF URINE

The most important point to determine in this connec-
tion is whether the immense amount of exercise during the
five days of the walk had any influence on the elimination
of water by the kidneys. This can be settled with tolerable
accuracy, inasmuch as the liquids taken each day were care-
fully measured.

First Period, Five Days before the Walk. — The
range of variation in the quantity of urine during this period
was not great, the extremes being 32.45 fl 5 (960 cc.)
and 46.15 flo (1.365 cc). The variations do not present
any definite relation to the quantity of liquids. On the
fourth day, with 32.45 fl 3 of urine, the liquids taken
amounted to 68.73 ^ 5- On the third day, w4th 46.15 flo
of urine, the liquids taken amounted to 55.56 fl o- On
the third day, when the quantity of urine was the greatest,
the meteorological record is the following: Thermometer,
highest, 42° Fahr., lowest, 29° Fahr. ; humidity (saturation
100) 61.36; "slight rain and slight snow at 6.15 p.m."
The humidity on that day was the greatest of the five.
On the fourth day, when the quantity of urine was the
least, the record was as follows: Thermometer, highest,
36° Fahr., lowest, 27° Fahr.; humidity 56.66; "snow-
squalls, clear evening." During this period the excess
of liquids taken must have been discharged through the
skin.

The average quantity of urine during these five days
was 37.84 fl o (1,134 cc). The average quantity of liquids
taken daily was 65.56 fl o (1,966.8 cc).

Second Period, Five Days of the Walk. — The
range of variation in the quantity of urine during this pe-
riod also was slight, the extremes being 43.60 fl§ (1,290
cc), on the fifth day, and 32.52 fl o (965 cc), on the
fourth day. The variations bore no definite relation to
the meteorological record. On the day of greatest dis-
charge of urine, the liquids taken amounted to 151.06 fl o-
On the day of the least urine, the liquids taken amounted
to 137.04 flo- During this period the relations between

EXCRETION OF NITROGEN 441

the quantity of urine and of liquids taken were pretty con-
stant: first day, urine, 42.09 flS; liquids taken, 171.67 flo;
second day, urine, 33.50 115; liquids taken, 136.40 flo;
third day, urine, 40.56 flo; liquids taken, 158.75 flo;
fourth day, urine, 32.52 flS; liquids taken, 137.04 flo;
fifth day, urine, 43.60 flo; liquids taken, 151.06 fl 5.

The average quantity of urine during these five days
was 38.46 flo (1,138 cc). The average quantity of liquids
taken was 150.40 flo (4.512 cc).

The average of 38.46 flo (1,138 cc.) for the five days
of the walk, against 38.14 fl o (i,i34 cc), for the five days
before the walk, shows that the walk of 317^ miles in fiv.e
days did not affect the quantity of urine, and that the
large quantities of liquids taken during that time must have
been discharged by the skin.

Third Period, Five Days after the Walk. — The
variations in the daily discharge of urine during this period
were very considerable, the extremes being 84.18 fl o (2,490
cc), on the third day, and 31.59 flo (937.5 cc), on the
iirst day. The variations bore no definite relation to the
meteorological record. There was no definite relation be-
tween the quantity of urine and the liquid ingesta. On the
third day, with 84.18 fl ,3 of urine, the liquids taken
amounted to 57.87 fl B; and on the first day, with 31.59 fl o
of urine, the liquids taken amounted to 46.74 fl 5. On
the second day the liquids taken amounted to 104.82 flo,
and the urine discharged, 46.14 fl o-

The average quantity of urine during these five days
was 58.14 fl o (1,720 cc). The average quantity of liquids
taken was 69.22 fl § (2,076 cc).

During the five days after the walk, for every 100 parts
of liquid ingesta the kidneys discharged 84 parts. During
the five days before the walk, for every 100 parts of liquid
ingesta the kidneys discharged 58 parts. This is probably
to be explained by the exercise of 8.2 miles daily for the
five days before the walk, which would increase the action
of the skin, while after the walk the exercise was only 2.2
miles daily.

It will not be necessar}^ to consider under a separate
head the variations in the specific gravity of the urine, as
this simply represents the solid constituents, which will be
taken up separately.
29

442 EXCRETION OF NITROGEN

INFLUENCE OF EXERCISE UPON THE ELIMINATION OF
NITROGEN, CHIEFLY IN THE UREA, AND THE RELATIONS
BETWEEN THE NITROGEN DISCHARGED AND THE NITRO-
GEN INGESTED

As regards the elimination of nitrogen, the investiga-
tions were undertaken chiefly with reference to the influ-
ence of the great muscular exertion during the five days
of the walk. In order to ascertain exactly the quantity
of nitrogen excreted at this time as compared with that
discharged under ordinary conditions, the nitrogen of both
the urea and feces was taken. The proportion of nitrogen
in the uric acid, creatin and creatinin of the urine is so
insignificant, as compared with the total discharge, that
it would hardly modify the results of the calculations. Dur-
ing the fifteen days Weston took food according to his
fancy. At certain times during the walk he took large
quantities of tea and coffee; but the results of the calcula-
tions show that the modifications, if any, in the discharge
of urea produced by these articles must have been greatly
overshadowed by those due to the muscular exercise. In
the discussion of this, the most important of the questions
involved, the influence of food will be treated of from a
secondary point of view. As regards this point there is
no difference of opinion. Nitrogenous food always in-
creases the elimination of urea; and so marked is this, that
many physiologists hold the view that urea is derived al-
most entirely from the food. This is one of the physiolog-
ical questions settled by these observations.

From the foregoing considerations it is evident that
the only accurate way to determine the modifications in the
elimination of nitrogen that are to be attributed to muscu-
lar exercise, is to calculate for each period, and for every
day of each period, the proportion borne by the nitrogen
in the urea and feces to the nitrogen of the food. It is
true that the influence of the food of one day may be pro-
longed for one or more days, and the same remark may
possibly apply to the exercise; but the periods of five days
each are sufficiently long to obviate any serious error from
this cause. I have learned, however, from these calcula-
tions, that a period much shorter would not be entirely
satisfactorv.

EXCRETION OF NITROGEN 443

The conclusions that I shall arrive at will all be drawn
from Tables A.^ B.^ C.^ for the first period; Tables A.^
B.- C.^ for the second period; and Tables A.^ B.^ C.^ for
the third period. Table D. gives the daily averages for
the three periods.

First Period, Five Days before the Walk. — For
the first day of this period the total nitrogen of the urea
and feces was 323.26 grains (20.945 grammes). The nitro-
gen of the food was 361.22 grains (23.404 grammes). For
every 100 parts of nitrogen of food, there were discharged
in the urea and feces, -89.49 parts. The exercise was fifteen
miles. The nitrogen of the food was about 30 per cent,
above the average for an ordinary man. The elimination
of nitrogen per 100 parts of the nitrogen of food was con-
siderably below the average.

On the second day the total nitrogen of the urea and
feces was 301.18 grains (18. 181 grammes). The nitrogen
of the food was 288.35 grains (18.682- grammes). For
every 100 parts of nitrogen of food, there were discharged
in the urea and feces, 104.45 parts. The exercise was five
miles. The nitrogen of the food of this day was a little
below the average.

On the third day the total nitrogen of the urea and
feces was 330.36 grains (21.405 grammes). The nitrogen
of the food was 272.27 grains (17.641 grammes), much be-
low the average for an ordinary man, which I put at 310
grains. For every 100 parts of nitrogen of food, there
W'Cre discharged in the urea and feces. 12 1.3 parts. The
exercise was five miles.

On the fourth day the total nitrogen of the urea and
feces was 300.57 grains (19.475 grammes). The nitrogen
in the food was 335.01 grains (21.706 grammes), a little
above the average for an ordinary man. For every 100
parts of nitrogen of food, there were discharged in the
urea and feces, 89.75 parts. The exercise was fifteen
miles.

On the fifth day the total nitrogen of the urea and
feces was 320.06 grains {20.'j}^y grammes). The nitrogen
of the food was 440.43 grains (28.536 grammes), much
above the average. For every 100 parts of nitrogen of
food, there were excreted in the urea and feces, 72.67 parts.
The exercise was one mile, with ten hours' sleep.

444 EXCRETION OF NITROGEN

Taking the averages for the five days, the nitrogen of
the urea and feces daily was 315.09 grains (20. 149 grammes).
The daily nitrogen of the food was 339.46 grains (21.994
grammes). For every 100 parts of nitrogen of food, there
were excreted in the urea and feces, 92.82 parts, which may
be taken as about the normal average under ordinary con-
ditions.

From these figures, the following conclusions may be
drawn :

I. Under ordinary conditions about 93 per cent of the
nitrogen of food is represented in the urea and feces; and
the remaining 7 per cent, may be put down to nitrogen
discharged in other ways and to an allow^ance for error in
the estimates, particularly in the food.

II. In view^ of the unusual power of endurance of Wes-
ton and his habit of walking long distances, I do not think
that the variations in the exercise during the five days are
to be regarded as sufficient to influence, to any great ex-
tent, the elimination of nitrogen; and I consider that these
variations are due chiefly to the nitrogen of the ingesta.
The influence of the food probably is manifested in a more
marked manner one or two days after than on the day on
which the excess of nitrogen is taken. This fact has been
recognized by physiologists, especially since the researches
of Lehmann, to which reference has already been made.*
On the first day there was about 30 per cent, of excess
of nitrogen of the food, and 89.49 parts of nitrogen dis-
charged per 100 parts of nitrogen taken in. On the sec-
ond and third days the nitrogen of the food was a little
below the average. On these days there was an average
of 1 1 1.65 parts of nitrogen discharged per 100 parts of
nitrogen taken in. On the fourth day the nitrogen of the
food was slightly in excess, with 89.75 parts 'per 100 dis-
charged. On the fifth day the nitrogen in the food was
very largely in excess (42 per cent.), with 72.67 parts per
100 discharged. The absolute quantity of nitrogen dis-
charged on the fifth day was large, but the proportion per
100 of the nitrogen of food was overbalanced by the large
quantity introduced.

What is the mechanism of the influence of nitrogenous

* Lehmann, " Physiological Chemistry," Philadelphia, 1855, vol. i., p. 150.

EXCRETION OF NITROGEN 445

food upon the discharge of nitrogen by the excretions?
Does the excremental nitrogen come from a direct change
of the nitrogenous constituents of the blood into urea in
the blood itself, or is it derived from the nitrogenous food
used, through the blood, in building up the nitrogenous
semisolids of the body, passing into the excretions through
the processes of nutrition and disassimilation?

Although the answers to these questions are perhaps
beyond the limits of actual demonstration, the attainable
facts point very strongly to the following:

The nitrogenous food occupies several hours in its di-
gestion and its appropriation by the blood, where it is
changed into the nitrogenous nutritive constituents of the
circulating fluid. The process of its appropriation by the
nitrogenous constituents of the tissues, particularly in the
muscular system, is probably slower still. The chief prod-
uct of disassimilation of the nitrogenous constituents of
the tissues is urea; and its separation is very slow and grad-
ual. This fact is illustrated by the slow accumulation of
urea in the blood after extirpation of the kidneys. If this
is the mechanism of the production of urea, the increase in
its quantity would be marked for a day or two after the in-
troduction of an excess of nitrogenous food; and this is a
fact demonstrated by actual observation. If the excess of
urea were directly formed in the blood from an excess of
nitrogenous food, being discharged by the urine and leav-
ing a stated and but slightly variable quantity resulting
from the actual disassimilation of the tissues, its increased
discharge from an excess of nitrogenous food would be
more rapidly developed.

Second Period, Five Days of the Walk. — On the
first day of this period Weston walked eighty miles, with
one hour of sleep. The total nitrogen of the urea and feces
was 357.10 grains (22.167 grammes). The nitrogen of the
food was reduced more than 50 per cent, below the average,
being only 151.55 grains (9.820 grammes). For every 100
parts of nitrogen introduced there were 235.63 parts of
nitrogen discharged.

This very great discharge of nitrogen in proportion to
the nitrogen of the food may be in part explained by the
large excess of nitrogen taken the day before; but by far
the greatest part can be attributed only to the extraordi-

446 EXCRETION OF NITROGEN

nary ninscnlar exertion and the consequent waste of mus-
cular tissue. The loss of weight on the first clay was 43.2
oz. (1,224.00 grammes).

On the second day Weston walked forty-eight miles,
with 4 hours and 28 minutes of sleep. The total nitrogen
of the urea and feces was 370.64 grains (24.015 grammes).
The nitrogen of the food was largely increased, being
265.92 grains (17.229 grammes). For every 100 parts of
nitrogen introduced, there were discharged, 139.39 parts.
On this day there was still a large excess of nitrogen dis-
charged; but the proportion per 100 parts of the nitrogen
introduced was reduced by the increase in the proportion
in the food. The excessive discharge of nitrogen on this
day is to be attributed almost exclusively to the muscular
exertion of that, and, perhaps, of the previous day.

On the third day Weston walked ninety-two miles, with
30 minutes of sleep. The entire quantity of nitrogen of
the urea (no feces were passed) was very large, amounting
to 397.58 grains (25.760 grammes), representing 851.95
grains (55.200 grammes) of urea, by far the largest quantity
discharged in any one of the five days. This corresponded
to the greatest amount of muscular exertion, a fact which is
very significant. The nitrogen of the food was slightly
diminished, amounting to 228.61 grains (14.812 grammes).
For every 100 parts of nitrogen introduced, there were dis-
charged, 173.91 parts. This excessive discharge of nitro-
gen can be attributed only to the muscular exertion. On
that day Weston took six pints of strong coffee, which,
if it had any effect, would have diminished the elimination
of urea.

On the fourth day Weston walked fifty-seven miles,
with one hour of sleep. The nitrogen of the urea and feces
was 348.53 grains (22.582 grammes). The nitrogen of the
food was on this day diminished to the minimum, being
only 144.70 grains (9.376 grammes). For every 100 parts
of nitrogen introduced, there were discharged, 240.86 parts,
the largest excess observed during the five days.

At 10.30 p. M., on this day, Weston broke down com-
pletely. He could not see the track and was taken stag-
gering to his room, having reached apparently the limit
of his endurance. His condition at that time, as shown by
the records, was as follows: He had lost in weight 83.2

EXCRETION OF NITROGEN 447

oz. (2.358.00 grammes), being reduced from 119.2 lbs. (54
k. 62 grammes) to 114 lbs. (51 k. 704 grammes). He had
taken a daily average of 197.70 grains (12.809 grammes)
of nitrogen in his food, while walking an average of sixty-
nine and a quarter miles per day, with an average of sleep
in each twenty-four hours of i hour and 44 minutes, for
four days. His daily average of nitrogen should have been
310 grains (about 20 grammes), not allowing for an in-
creased quantity demanded to supply the waste engen-
dered by his excessive muscular exertion. He had dis-
charged for every 100 parts of nitrogen introduced, a daily
average of 186.37 parts for four days. The calculations,
as well as the general condition of the system, show that
the period had probably arrived when repair of the mus-
cular tissue had become absolutely necessary.

If these facts are to be accepted — and leaving the widest
margin for inaccuracy in the estimates, they can not in-
volve any considerable error — it is difBcult to come to any
other conclusion than that excessive and prolonged mus-
cular exercise increases largely the excretion of nitrogen,
and that the excess of nitrogen discharged is due to an
increased disassimilation of the muscular substance; and
it is to be remembered that the experiments upon which
this statement is based were made with a diet regulated
entirely by the wishes of the person under observation.

On the fifth day, after 9 hours and 26 minutes of sleep,
the system reacted completely, and Weston walked forty
and a half miles. The nitrogen of the urea and feces was
2i'}i2.'j'j grains (21.561 grammes). The nitrogen of the food
was increased 165 per cent., being 383.04 grains (24.818
grammes). For every 100 parts of nitrogen of food, there
were discharged, 84.27 parts. The absolute quantity of
nitrogen discharged was still very great; but the proportion
to the nitrogen introduced was reduced by the large quan-
tity in the food.

On this day, when there was apparent reaction after the
complete prostration of the fourth day, the system seemed
to appropriate nitrogen with avidity, to repair the impov-
erished muscular tissue. The weight was increased on this
day by 28 oz. (793 grammes).

A study of the averages for the five days of this period
develops points of much importance, some of which have

448 EXCRETION OF NITROGEN

already been considered in connection with the variations
in weight:

I. The absokite discharge of nitrogen by the urea and
feces for each day, without considering the nitrogen of the
food, is in a nearly uniform proportion to the number of
miles walked. This proportion is but little disturbed if it
is assumed that the influence of the ingestion of nitrogen
is prolonged for a period of twenty-four to forty-eight
hours.

II. During the walk of 317^ miles in five consecutive
days, for every 100 parts of nitrogen taken in with the
food, there were discharged in the urea and feces, 153.99
parts, against 92.82 parts per 100 for the five days before
the w-alk, and 84.63 parts per 100 for the five days after
the walk.

III. The actual loss of weight during the five days of
the walk, was 3.45 lbs. (1,565.00 grammes). The total
quantity of nitrogen discharged in the urea and feces during
this period, in excess of the nitrogen taken in with the
food, was 633.80 grains (40.030 grammes). Assuming that
3 parts of this nitrogen represent the waste of 100 parts
of muscular tissue, the loss of muscular tissue calculated
from the nitrogen excreted would be 3.018 lbs. (1.334.33
grammes), leaving only 0.43 of a pound (230.67 grammes)
unaccounted for, which might be fat or water.*

Third Period, Five Days after the Walk. — The
record of the fifth day of the second period shows that the
system had already begun to recuperate after the depres-
sion of the fourth day, notwithstanding the walk of forty
and a half miles. The explanation of this is to be found
in the long sleep and the quantity of nitrogenous food
taken. During the third period the exercise was practically
nothing, being only 2.2 miles daily; the sleep averaged 8
hours and 29 minutes; and the nitrogen of the food aver-
aged 440.93 grains (28.569 grammes). Weston did noth-
ing but eat, sleep and amuse himself, and this w'as a period
of complete bodily and mental repose, very favorable to
recuperation after the muscular exertion of the live days
before. At the end of the five days the weight had in-
creased to 120.75 lbs. (54 k. 765 grammes), 0.25 of a pound

* See the section on variations in weight.

EXCRETION OF NITROGEN 449

(110.00 grammes) above the weight at the beginning of the
observations. Immediately after the walk Weston felt
perfectly well and continued well for the five days, with the
exception of a slight headache on the afternoon and even-
ing of the fifth day. He smoked five to seven cigars daily,
but took no alcoholic stimulants. His diet was normal in
variety, but on some days the quantity of solid food was
very large.

On the first day the nitrogen of the food was 385.65
grains (24.987 grammes), about 64 per cent, above the
average for the five days of the walk. The nitrogen of the
urea and feces was 295.70 grains (19.159 grammes), about
18 per cent, below the average for the five days of the walk.
This reduction in the amount of nitrogen excreted is sig-
nificant. For every 100 parts of nitrogen of food, there
were discharged in the urea and feces, 76.68 parts.

On the second day the nitrogen of the food was much
increased, being 499.10 grains (32.338 grammes). The
nitrogen of the urea and feces was 358.81 grains (23.248
grammes). For every 100 parts of nitrogen of food, there
were discharged, 71.81 parts.

On the third day the nitrogen of the food was dimin-
ished, though it still largely exceeded the standard for a
man under ordinary conditions. On this day it was 394.83
grains (25.582 grammes). The nitrogen of the urea and
feces was largely increased, being 409.87 grains (26.556
grammes). For ever\' 100 parts of nitrogen of food, there
were dischr^-ged, 103.81 parts. This excess of nitrogen
discharged is to be attributed to the large quantity of nitro-
gen taken with the food on the day before.

On the fourth day the nitrogen of the food was in very
large quantity, being 641.71 grains (41.578 grammes), more
than double the average for a man under ordinary condi-
tions. The nitrogen discharged in the urea and feces was
382.89 grains (24.808 grammes). For every 100 parts of
nitrogen of food, there were discharged, 59.67 parts. This
proportion was reduced by the very large quantity of nitro-
gen taken with the food.

On the fifth day the nitrogen of the food was reduced
to a little below the average for a man under ordinary con-
ditions, being 283.35 grains (18.359 grammes). The nitro-
gen of the urea and feces was 418.49 grains (27.125

450 EXCRETION OF NITROGEN

grammes), much more than the discharge on any other
day of the fifteen. For every lOO parts of nitrogen of
food, there were discharged, 147.69 parts. This active
discharge of nitrogen is explained by the large amount
taken in the food on the previous day. On this day, at
midnight, the observations were ended.

The daily observations during this period, taken in con-
nection with those during the five days before the walk,
seem to establish the following with relation to the influ--
ence of nitrogenous food on the excretion of nitrogen:

Every day that an excess of nitrogenous food was taken,
it was followed, on the succeeding day, and on one occa-
sion on the succeeding two days, by a largely increased
discharge of nitrogen in the urea and feces, the discharge
on these days exceeding the amount taken in the food; but
the general average for five days, during the period of five
days before the walk and the period of five days after the
walk, was 85 to 93 parts of nitrogen discharged, for every
100 parts of nitrogen introduced.

The average for the five days after the walk shows an
introduction of 440.93 grains (28.569 grammes) of nitrogen
daily, an excess of about 42 per cent, over the average for
a man under ordinary conditions. For every 100 parts of
nitrogen in the food, the average daily excretion, during
this period, was 84.63 parts.

INFLUENCE OF EXERCISE UPON THE ELIMINATION OF

URIC ACID

The results of the observations during the three periods,
as regards the influence of the exercise during the five
days of the walk and the influence of food during the five
days before and the five days after the walk, are unsatis-
factory and are interesting chiefly from a negative point of
view.

The quantities of uric acid for each day present very
wide variations. For example, on the fourth day of the
walk, the exercise being fifty-seven miles, the quantity was
9.21 grains (0.597 of a gramme), the greatest amount for
any one day; and on the second day of the walk, the exer-
cise being forty-eight miles, the uric acid was 0.14 of a
grain (0.009 o^ ^ gramme) ; the smallest amount for any one

EXCRETION OF NITROGEN 451

day. On the second day of the first period the quantity
was 4.03 grains (0.261 of a gramme); and on the third day
after the walk the quantity was 0.31 of a grain (0.02 of a
gramme). I have carefully compared the quantities for each
day with the exercise and can find no definite relation be-
tween them. I have also carefully compared the quantities
for each day with the character and quantity of food, but
with no more satisfactory result. Inasmuch as on certain
days during the walk Weston took large quantities of cof-
fee, it occurred to me that this might influence the uric
acid; but I did not find any confirmation of this in the tables.
I calculated also for each day the proportion of uric acid per
100 parts of urea discharged, with the view of confirming
or disproving the idea that uric acid represents urea in an
imperfect condition of oxidation; but the results of these
calculations were also unsatisfactory. Finally I compared
the sleep and the meteorological record with the uric acid
and could establish no relation between them. The varia-
tions were so irregular that it was impossible to trace any
influence upon the uric acid due to food or exercise, even
if it is assumed that the influence might be protracted for
a period of one or more days.

As it is impossible to draw any positive conclusions
from a comparison of the quantities of uric acid excreted
day by day, I can only refer to the averages for the three
periods of five days each.

The average daily excretion of uric acid for the five
days before the walk was 2.26 grains (0.127 of a gramme).
The proportion of uric acid per 100 parts of urea for this
period was 0.360 of a part.

The average daily excretion for the five days, walking
in all 317^ miles, was 3 grains (0.194 of a gramme). The
proportion of uric acid per 100 parts of urea for this period
was 0.415 of a part.

The average daily excretion for the five days, walking
walk was 1.42 grains (0.082 of a gramme). The proportion
of uric acid per 100 parts of urea for this period was 0.195
of a part.

These results, in view of the unexplained daily varia-
tions in the uric acid, are not sufficiently definite to lead
to any positive conclusions. So far as they go, they show
an increase in the uric acid of about 33 per cent, during

452 EXCRETION OF NITROGEN

the period of extraordinary muscular exertion. During
the period of complete muscular inactivity, with an excess
of food, the excretion was diminished by about one-half.
The observations have developed, however, the follow-
ing negative facts:

I. There was no apparent relation between the increase
of urea and of uric acid, except that both were increased,
with the other solid constituents of the urine. In other
words, in increasing the urea by exercise, there is no evi-
dence that uric acid is oxidized and converted into urea;
for if that had been the case, with the increase in the quan-
tity of urea, there would have been a diminution in the
proportion of uric acid per lOO parts of urea; and this did
not occur.

II. It was not shown that the quantity of nitrogenous-
food has any influence upon the elimination of uric acid;
unless it be assumed that the diminution in the uric acid,
during the period of inactivity and excess of nitrogenous
food, was due to the food alone.

The important physiological results which I hoped to
arrive at by studying the uric acid, with the applications
of such results to pathological conditions, were not real-
ized; and it must be admitted that positive knowledge of
the relations of uric acid to nutrition and disassimilation
has not been advanced by these researches, although some
important negative facts have been developed.

IXFLUEXCE OF EXERCISE UPON THE ELIMINATION OF
INORGANIC SALTS BY THE KIDNEYS

In Studying the variations in the proportions of inor-
ganic salts in the urine, it will be seen that the phosphoric
and the sulphuric acid are generally in about the same ratio
to each other, their excretion being apparently increased
and diminished by the same causes. With the chloride of
sodium, however, it is dififerent. For example, on the third
day of the walk the quantity of phosphoric acid was large,
while the chloride of sodium was in very small quantity,
nearly at the minimum. As it is not improbable that differ-
ent causes may influence, on the one hand, the phosphoric
and the sulphuric acid, and on the other, the chloride of
sodium, it will be proper to consider the chloride by itself.

EXCRETION OF NITROGEN 453

Phosphoric and Sulphuric Acid. — It is undoubted-
ly true that the excretion of the phosphates and sulphates
by the kidneys is largely influenced by the quantity of
these salts in the food. They must, however, pass into the
urine in one or both of two ways; either directly from the
blood, the salts being taken up by absorption without be-
coming a part of the tissues, or they may come from the
tissues, by a process analogous to that of the production
of urea. If these salts passed directly from the blood, their
elimination would be almost entirely under the influence of
the food; and this influence would be apparent soon after
their introduction. If the phosphates and sulphates of the
urine are derived from the tissues in the process of disas-
similation, when this process is increased in activity, as it
was during the five days of the walk, the influence of the
food would probably be overshadowed by the exaggerated
activity of disassimilation, due to the extraordinary mus-
cular work. It is not possible to subject these questions
to rigidly scientific inquiry without estimating exactly the
phosphoric and the sulphuric acid in the food. This was
impracticable; but the solid food was so little changed in
its character during the different days of the three periods,
that the variations in its quantity will be to a certain extent
a measure of the introduction of the inorganic salts.

First Period, Five Days before the Walk. — Dur-
ing this period the range of variation from day to day was
between 43.01 and 67.00 for the phosphoric acid, and be-
tween 38.18 and 51.50 for the sulphuric acid. With one
exception, these two acids varied from day to day in about
the same ratio. On the first day the phosphoric acid was
in large quantity, with a small quantity of sulphuric acid.
With the exception of the fifth day both the phosphoric
and the sulphuric acid were varied in a nearly constant
ratio to the variations in the nitrogenous food, being in-
creased with the food and rice versa. On the fifth day,
when the quantity of nitrogenous food was the greatest,
both the phosphoric and the sulphuric acid were below the
average for the five days. On this day the exercise was
very little, only one mile.

The most marked and constant variations during this
period were with the exercise, especially in the phosphoric
acid. On the first day the exercise was fifteen miles; the

454 EXCRETION OF NITROGEN

phosphoric acid was 51.46 grains (3-334 grammes), the
average for the five days being 50.14 grains (3.262
grammes), and the sulphuric acid was 38.37 grains (2.486
grammes), the average being 41.57 grains (2.693 grammes).
On the fourth day the exercise was fifteen miles; the phos-
phoric acid was 67 grains (4.341 grammes), and the sul-
phuric acid, 51.50 grains (3.337 grammes). On this day
the loss of weight w-as 24 oz. (687 grammes), the greatest
loss for any one of the five days. On the second and third
days both the phosphoric and the sulphuric acid were
slightly below the average for the five days, with five miles
of exercise each day. On the fifth day, with ten hours of
sleep and one mile of exercise, the phosphoric acid was
43.01 grains (2.787 grammes), and the sulphuric acid, 38.18
grains (2.474 grammes), the smallest quantities during the
five days.

During this period the increase in the phosphoric and
the sulphuric acid with the exercise w^as constant.

Second Period, Five Days of the Walk. — During
this period the ratio of variations between the phosphoric
and the sulphuric acid w-as constant, with the exception of
the fifth day, when the quantity of sulphuric acid was a
little greater than on the fourth day, wdiile the phosphoric
acid was less. During this period there was no definite
relation between the quantities of these two acids and the
nitrogenous food; the influence of the food being appar-
ently overshadowed by the exercise. The relations be-
tween the phosphoric acid and the exercise were nearly
absolute. Taking the exercise from the highest to the
lowest points, the relations were as follows:

Third day.
First day.
Fourth day.
Second day.
Fifth day.

Exercise

92 miles.
80 "

57 "
48 "
4oi "

H3PO4

102.25

84.95
66.90

72.14

57.49

grains (6.625

" (5504
(4.296

" (4674
" (3.725

gram

mes).
).
)-
).
).

The variations in

the sulphuric acid were not

so regular :

Third day.
First day.
Fourth day.
Second day.
Fifth day.

Exercise

92 miles.
80 "

57 "
48 "
40^^ "

H.SO4

63.71

73-39
32.66
56.90
40.84

grains (4.128

" (4-755
" (2.1 16
" (3.687
" (2.646

gram

mes).
).
).
).
).

These calculations show a decided and nearly absolute
relation between the excretion of phosphoric acid and the

EXCRETION OF NITROGEN 455

exercise. On the fourth day, with fifty-seven miles of exer-
cise, the nitrogen of the food was about forty-six per cent,
less than on the second day, with forty-eight miles of exer-
cise. This will perhaps account for the diminished excre-
tion during the day of less exercise.

As regards sulphuric acid, the conclusions are about
the same as for phosphoric acid. The diminished excre-
tion on the second day is also accounted for by the small
quantity of nitrogenous food taken on that day.

Third Period, Five Days after the AValk. — Dur-
ing this period the exercise was practically nothing; and
this element does not, therefore, enter into the calcu-
lation of the variations of the inorganic constituents of
the urine. Although the variations in the phosphoric
and the sulphuric acid were considerable, as were the
daily variations in the nitrogenous food, there seemed
to be no definite relation between them. I shall there-
fore give for this period simply the extremes and the
averages.

On the third day the quantities both of phosphoric and
of sulphuric acid were the greatest. The phosphoric acid
was 105.68 grains (6.847 grammes). The sulphuric acid
was 53.57 grains (3.471 grammes). On the first day the
phosphoric acid was least in quantity, being 29.06 grains
(1.833 grammes), with 49.53 grains (3.209 grammes) of
sulphuric acid. On the second day the sulphuric acid was
least in quantity, being 46.07 grains (2.985 grammes), with
46.93 grains (3.041 grammes) of phosphoric acid.

The averages for the five days of this period were as
follows: Phosphoric acid, 56.89 grains (3.674 grammes);
sulphuric acid, 49.02 grains (3.176 grammes).

Averages for the Three Periods. — The averages
for the three periods of five days each show the influence
of exercise upon the elimination of phosphoric and sul-
phuric acid; and the averages for the period of five days
before the walk and the period of five days after the walk
show the influence of food, probably attributable to the
phosphates and sulphates combined with the nitrogenous
matters.

For the first period, five days before the walk, the aver-
age discharge of phosphoric acid was 50.14 grains (3.262
grammes), and of sulphuric acid, 41.57 grains (2.693

456 EXCRETION OF NITROGEN

grammes). The average quantity of nitrogen in the food
was 339.46 grains (21.994 grammes).

For the second period, five days of the walk, the aver-
age discharge of phosphoric acid was 76.63 grains (4-965
grammes), and of sulphuric acid, 53.50 grams (3.666
grammes). The average quantity of nitrogen in the food
was 234.76 grains (13.21 1 grammes).

For the third period, five days after the walk, the aver-
age discharge of phosphoric acid was 56.89 grains (3.674
grammes), and of sulphuric acid, 49.02 grains (3.176
grammes). The average quantity of nitrogen in the food
was 440.93 grains (28.569 grammes).

These averages show that the walk of 317^ miles in
five consecutive days increased the excretion of phosphoric
acid more than 50 per cent, over the excretion under ordi-
nary conditions, notwithstanding that the nitrogenous food
was diminished 31 per cent. Under the same conditions
there was an increase of about 30 per cent, in the excretion
of sulphuric acid. The influence of exercise upon the ex-
cretion of the phosphates and sulphates, irrespective of the
composition of the food, can hardly be doubted.

A comparison of the averages for the first period, five
days before the walk, and the third period, five days after
the walk, shows an increase in the excretion of phosphoric
acid, for the third period, of 13.4 per cent., with an increase
of 30 per cent, in the quantity of nitrogenous food. Under
the same conditions the excretion of sulphuric acid was in-
creased by 19.2 per cent.

Chloride of Sodium. — In the absence of exact esti-
mates of the quantities of chloride of sodium contained in
the food of each day, there is little to be learned from the
variations in excretion of this salt by the kidneys. Such
estimates were manifestly impracticable. The salt used as
a condiment was averaged for the four days of the first
period and for the fifth day of this period, with the five
days of the walk. For the five days after the walk the
quantity of salt used was weighed each day. I can form
no definite idea of the salt used in cooking for the five days
before the walk and the five days after the walk; but on
some of the days of the walk, particularly the third and
fourth, the diet consisted largely of beef-essence and oat-
meal-gruel. No salt was added to the beef-essence, which

EXCRETION OF NITROGEN 457.

was prepared under my own direction, and very little was
used in the preparation of the oatmeal-gruel.

First Period, Five Days before the Walk. — The
average quantity of salt used as a condiment during this
period was 34.5 grains (2.235 grammes). During the tive
days the proportion of nitrogenous food and the elimina-
tion of chloride of sodium presented no definite relation
to each other. The variations in the chloride of sodium
of the urine were not considerable and had no definite
relation to the exercise. The greatest quantity was on the
first day. being 195.02 grains (12.636 grammes); and the
smallest quantity was on the fourth day, when it was 106.68
grains (6.912 grammes). In the absence of any definite
relation between the excretion of chloride of sodium and
either the food or the exercise, I can use only the average
for this period, which was 159.45 grains (10.331 grammes).

Second Period, Five Days of the Walk. — There
are some interesting points connected with the elimina-
tion of chloride of sodium during this period. The ni-
trogenous food, which contained nearly all the chloride of
sodium, was diminished by 31 per cent., and the average
quantity of salt used as a condiment was 35 grains (2.265
grammes). The average elimination of chloride of sodium
by the kidneys was only 65.08 grains (4.217 grammes);
but a large quantity must have been eliminated by the skin,
the average cutaneous and pulmonary exhalation daily
being 138.41 oz. (3,875.18 grammes), against 61.63 oz.
{1,690.91 grammes) for the five days before the walk, and
62.82 oz. (1,706.78 grammes) for the five days after the
walk.

On the third day, when the food contained probably
the minimum proportion of salt, the salt of the urine was
reduced to 44.45 grains (2.88 grammes), about 32 per cent,
below the average for the five days. On the fourth day
it is probable that a little more salt was taken with the food.
On this day the exercise was fifty-seven miles; but it was
on this day that W^eston broke down and was forced to
take a long rest. The chloride of sodium for this day was
reduced to 28.78 grains (1.865 gramme), nearly 56 per
cent, below the average. On the next day, when reaction
took place, the salt returned to about the average. In
A-iew of the disappearance of the chloride of sodium of the
30

4S8 EXCRETION OF NITROGEN

urine in certain febrile conditions, this diminution in its
quantity on the day of great constitutional depression
is interesting, although its exact significance is not ap-
parent.

Third Period, Five Days after the Walk. — The
variations in the chloride of sodium of the urine during
this period were very great. The smallest quantity was
on the first day, when it was 66.41 grains (4.303 grammes).
The largest quantity was on the third day, when it w'as
622.58 grains (40.338 grammes). The quantity of urine
on this day was 84.18 fi .") (2,490 cc). I could not connect
these variations either with the diet or with the salt used
as a condiment, which was weighed each day and varied
considerably. The only point connected with the daily
variations during this period is the small quantity on the
day next after the walk, when it w^as only 66.41 grains
(4.303 grammes), while the salt actually used as a condi-
ment on that day was 65.62 grains (4.252 grammes).

The average daily quantity of chloride of sodium of the
urine for this period was 312.40 grains (20.241 grammes).
The nitrogenous food was increased by 30 per cent, over
the average for the five days before the w-alk. The average
quantity of salt used as a condiment was 42 grains (2.721
grammes), an increase of nearly 22 per cent, over the aver-
age for the five days before the w-alk.

Averages for the Three Periods. — The averages
for the three periods of five days each are as follows:

First period, five days before the walk; 159.45 grains
(10.331 grammes).

Second period, five days of the walk, 65.08 grains (4.217
grammes).

Third period, five days after the walk. 312.40 grains
(20.241 grammes).

These averages show a great diminution in the chloride
of sodium of the urine during the walk, due in a great
measure, undoubtedly, to a diminution in the quantity of
salt ingested. In the absence of exact estimates of the
quantity of salt introduced, it is impossible to state defi-
nitely the influence of exercise on its elimination by the
kidneys. Probably it is diminished, a much larger quantity
than usual being eliminated by the skin. An argument
in favor of this view is the small quantity in the urine the

EXCRETION OF NITROGEN 459

day next after the walk, when a large quantity was intro-
duced with the food.

The only explanation I can offer of the great increase
in the chloride of sodium during the five days after the
walk is in the larger quantity taken with the food, and
possibly the cessation of the influences which diminished
it in the urine during the five days of the walk.

ABNORMAL MATTERS IN THE URINE

There is very little to be said in regard to the abnormal
'matters discovered by microscopical examination of the
urinary sediments. During the first period, five days be-
fore the walk, there was a constant deposit of octahedra
of oxalate of lime. During the second period, five days
of the walk, oxalate of lime was found daily. On the fifth
day of this period, in addition to oxalate of lime, there
was a small quantity of the amorphous phosphates. The
oxalate of lime continued during the third period, five
days after the walk, with the exception of the fourth day,
when there were no abnormal matters. On the first day
of this period the sediment contained, in addition to oxa-
late of lime, amorphous urates in small quantity. On the
second and the third day of this period, in addition to
oxalate of lime, the sediment contained crystals of uric
acid. On these days the quantity of uric acid in the urine,
determined by analysis, was very small, and the crystals
were probably due to increased acidity of the urine. I can
ofifer no explanation of the presence of any of these crystals
in the urine nor can I connect them with any of the con-
ditions observed.

On the second and the third day of the third period,
five days after the walk, the urine contained a trace of sugar.
There was no increase in the quantities of starchy and
saccharine matters in the food on these days to account
for the sugar, the presence of which can not readily be
explained.

In conclusion, it is evident, from the results of these
investigations, that the question of the influence of muscu-
lar exercise upon the elimination of nitrogen can be accu-
rately studied only by comparing the nitrogen of the food
with the nitrogen of the excretions; and this should be done

46o EXCRETION OF NITROGEN

if possible upon a perfectly physiological diet. It is indis-
pensable, also, to extend the experiments over periods of
several days each; otherwise the results will necessarily be
confused and unsatisfactory. The observations in regard
to the body-weight and various other conditions were
necessary to control the more important points to be con-
sidered. The great amount of material collected and its
analysis and tabulation have involved considerable labor,
which, however, has been rewarded by important conclu-
sions of a definite and positive character.

At the risk of presenting to the reader an unattractive
mass of statistics, I have thought it proper to publish, not
only the general facts and deductions, but the exact data
collected, arranged in a form that may be useful to other
investigators. I feel confident that I shall not be re-
proached for tediousness of detail by those who are inter-
ested in the important physiological questions involved,
particularly those who have carefully studied the literature
of these questions for the past few^ years.

XX

SUPPLEMENTARY REMARKS "ON THE EF-
FECTS OF SEVERE AND PROTRACTED
MUSCULAR EXERCISE; WITH SPECIAL
REFERENCE TO ITS INFLUENCE ON THE
EXCRETION OF NITROGEN"

Published in the " Journal of Anatomy and Physiology," Cambridge and
London, for October, 1876.

In June, 1871 I published in the " New York IMedical
Journal " an account of a series of observations made upon
Weston, the pedestrian, during one of his feats of endur-
ance. My researches have lately been in part repeated and
confirmed in England by Dr. Pavy. My original observa-
tions were made with the utmost care, and they involved
a great deal of labor. They were most decidedly opposed,
in their results, to the modern view regarding the influence
of muscular exercise on the excretion of urea, which is
based upon the experiments of Fick and Wislicenus, made
in 1866, and upon other observations apparently confirma-
tory of the notion that the elimination of urea is not in-
creased by muscular work. This view I believe to be in-
correct; and I regard the experiments upon which it rests
as imperfect, faulty and made under unphysiological con-
ditions.

The question of the influence of muscular exercise on
the elimination of nitrogen being of great importance in
its pathological as well as in its physiological relations,
it was to be expected that conclusions opposed to the
generally-accepted ideas, even when deduced from very
extended experiments, would be viewed with distrust
and receive adverse criticism. I have not failed to real-
ize this expectation; although it seemed to me that my
conclusions could not be successfully controverted with-

461

462 EXCRETION OF NITROGEN

out a denial of the accuracy of my experimental data.
I shall here refer only to the criticisms of Dr. Pavy,
as he is now the one physiologist who is in a position
to judge, from his own knowledge, of the reliability
of my observations. These criticisms, however, seem to
me to be general rather than definite and positive. They
are summed up substantially in the following para-
graph, quoted from Dr. Pavy's work on " Food and
Dietetics ": —

" Now, apart from the fact that a marked deviation from the
physiological state existed when the results upon which the con-
clusions are based were yielded, is there anything in the results
to show that in reality we have more to deal with than simply a
consumption of nitrogenous material within the system beyond the
supply for the time from without? Taking the figures throughout,
there is not much more to be seen than a difference occasioned by a
falling off in the amount of nitrogen ingested during the first four
days of the walk ; and it is well known that when the ingesta do
not furnish what is wanted for meeting the expenditure going on
(as during inanition), the resources of the body are drawn upon,
and the nitrogenous matter existing in the various parts — both
solids and fluids — wastes or yields itself up as well as the rest. On
the fifth day, after a prolonged sleep, which appears to have re-
stored the flagging powers, the previous relation was reversed.
The food ingested afforded more than enough to meet the require-
ments. There was a gain of if pound in body- weight, and accord-
ing to the figures, the nitrogen discharged fell short by 50.27 grains
of that which entered, notwithstanding a walk of forty miles and
a half was performed." *

This paragraph, without a knowledge of the details of
my experiments, may seem obscure. I think Dr. Pavy
intended to reason as follows: — Although I had demon-
strated, for the first four days of a feat performed by Wes-
ton in which he had walked, the first day 80 miles, the sec-
ond day 48 miles, the third day 92 miles and the fourth day
57 miles, that there was a large increase in the nitrogen
excreted over the nitrogen of food, it is assumed by Dr.
Pavy that this apparent excess was due to a deficient inges-
tion of nitrogen and not necessarily to an increase in the
excretion of nitrogen. The fact is that comparing four
days, during which 277 miles were walked, with four days
before, during which 26 miles were w^alked, in four days,

* Pavy, " Food and Dietetics," Philadelphia, 1874, p. 71.

EXCRETION OF NITROGEN 463

walking 26 miles, there were 1,336.06 grains of nitrogen
in the food, against 790.78 grains during four days, walk-
ing 277 miles, or a deficiency in the nitrogen of food dur-
ing the latter period of 545.28 grains. During the four
days, walking 26 miles, the nitrogen excreted was 1,252.17
grains, against 1,473.85 grains during the four days, walk-
ing ^yy miles, or an excess of nitrogen excreted of 221.68
grains. It is evident that the excessive exertion of walk-
ing 277 miles in four consecutive days induced an increase
in the excretion of nitrogen; not only sufificient to equal
the deficiency of the nitrogen of food, but a considerable
excess. The excess of the nitrogen excreted during the
four days, walking 277 miles, over the four days, walking
26 miles, irrespective of the nitrogen ingested, was 221.68
grains; and the excess of nitrogen excreted during the four
days, walking 277 miles, over the nitrogen ingested dur-
ing the four days, walking 26 miles, was 137.79 grains. It
seems to me that the figures and deductions which I gave
in my original article, in which I show the effects of pro-
longed and severe muscular exercise on the excretion of
nitrogen, not only in absolute quantity but in proportion
to the nitrogen ingested, are sufficiently clear and distinct;
and the complications in these deductions, if they exist,
are due to the process of reasoning from my figures em-
ployed by Dr. Pavy. It does not appear that any physi-
ological demonstration could be more positive than that
of the proposition that muscular exercise increases, not
only the absolute quantity of nitrogen excreted, but the
proportionate quantity of nitrogen eliminated to the
nitrogen of food.

My first impression, in studying the experiments of Fick
and Wislicenus, was that the observations on the influence
of exercise upon the elimination of nitrogen were made
upon a purely non-nitrogenous diet on account of the labor
and difficulty attending an accurate estimation of the nitro-
gen of food; but it now seems to me that this was not the
only idea under which this method of experimentation was
adopted. It is a seductive, and was a more or less novel
idea, that the animal organism, after it has become fully
developed, is a machine which consumes food as fuel, and
that it does not constantly wear out its own substance by
work and repair itself by the ingesta. With this view, it

464 EXCRETION OF NITROGEN

would seem possil)Ie to reduce the values of food to
mathematical accuracy, calculating the heat-units, foot-
pounds, etc., of various articles of diet. Such calculations
would be very indefinite for any restricted period of time,
adopting the view that the nitrogenous constituents of the
body wear and are consumed with muscular work and that
they are regenerated by the nitrogenous matters of food.
A necessary basis for an accurate estimation of heat and
work-units of food is the idea that food is directly con-
sumed in the production of heat and in work. While cal-
culations of these units with mathematical accuracy would
be very desirable as giving definite form to ideas of the
value of food, they still want a positive basis in fact. In
carrying out this idea, it seems to me that the value of
many of the experiments is made to depend on the assump-
tion of the truth of the proposition which they are in-
tended to support.

In view of the importance of the results obtained by
me, and, as I believe, confirmed by the recent observations
of Dr. Pavy, it would be interesting to assimilate and com-
pare the two sets of observations, the more so as I could
scarcely have hoped that independent researches would
have been made under the same unusual conditions; viz.,
the same subject undertaking a similar feat of endurance.
In the account published by Dr. Pavy thus far I do not
find any reference to the results obtained by me in 1870
and published in 187 1. If I should not be anticipated by
Dr. Pavy, I shall be interested to place the figures of the
two series of observations side by side; but I hope that Dr.
Pavy, who is now fully prepared to criticise my results, will
give them the study and attention that he bestowed upon
them when he had had no opportunity to personally test
their accuracy. In the calculations which I made of the
quantities of nitrogen of food I used the same estimates
for all the three periods, before, during and after the walk.
If any errors existed in these estimates, such errors would
have equal value in the difTerent periods and would not
materially change the comparative results. It would be
interesting to use these same estimates in calculating the
nitrogen of the food taken while Weston was under the
observation of Dr. Pavy.

EXCRETION OF NITROGEN 465

CORRECTIONS IN THE TABLES PUBLISHED IN 187I*

In calculating the proportion of nitrogen excreted to
the nitrogen of food, I fell into an error sufficiently serious
to demand correction, although it does not affect the
general conclusions deduced from my observations. I
first calculated the quantity of nitrogen excreted for every
hundred parts of nitrogen of food, for each day, by multi-
plying the nitrogen excreted by lOO and dividing by the
nitrogen of food, which gave correct results; but in calcu-
lating the average proportions of nitrogen excreted for the
five days before the walk, five days of the walk and five
days after the walk, I added for each period the propor-
tionate excretion of nitrogen for the five days and obtained
the average by dividing by five. This was an error, as I
was using relative and not absolute quantities. I fell into
this error simply because the process w^as a little easier
than to divide the average amount of nitrogen excreted for
the five days by the average amount of nitrogen ingested
for the same period.

* The corrections in the tables — which followed in this article as originally
published — have been made in Article XIX., as republished here.

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