Cornell Aniversity Dibrary

BOUGHT WITH THE INCOME
FROM THE

SAGE ENDOWMENT FUND

THE GIFT OF

Henry W. Sane

1891

6421

‘ita

olin,anx

Cornell University

Library

The original of this book is in
the Cornell University Library.

There are no known copyright restrictions in
the United States on the use of the text.

http :/Awww.archive.org/details/cu31924031268091

Essays on BacrertoLocy

AND ITS

RELATION TO THE PROGRESS OF MEDICINE

BY

THEODORE POTTER, A.M., M.D.

1
PROFESSOR OF PATHOLOGY AND BACTERIOLOGY (IN THE MEDICAL COLLEGE OF INDIANA,
INDIANAPOLIS UNIVERSITY; MEMBER OF CONSULTING STAFF, CITY HOSPITAL AND
THE DEACONESS HOSPITAL; CONSULTING PHYSICIAN FOR DISEASES
OF THE CHEST, INDIANAPOLIS CITY DISPENSARY

THE INDIANA MEDICAL JOURNAL PUBLISHING COMPANY
INDIANAPOLIS
1898

PRESS OF
SENTINEL PRINTING COMPANY,
INDIANAPOLIS, IND.

—

DEDICATION

To My FaTHER
Tue ReverenD LupLtow Day Porter, D. D., Lit. D.

IN THE LANGUAGE OF THE HOoosIER SCHOOLMASTER
“THE MAN I KNOW BEST, AND THE
BEST MAN I KNOW”

®
THIS LITTLE BOOK IS AFFECTIONATELY INSCRIBED

VII.
VIII.

XI.

CONTENTS

Tur Germ THEORY oF DIsEAsE

SoME oF THE PROBLEMS OF BACTERIOLOGY . é
Speciric DisEAsSES AND SPECIFIC BACTERIA .
SELF-LIMITATION AND IMMUNITY . ‘ Z
THE CoNTEST AGAINST INFECTION . i
RETROSPECT AND PROSPECT OF PROGRESS : F
Anti-Toxic S—eruM THERAPY . ; F F

Serum THERAPY IN DIPHTHERIA AND OTHER
DISEASES

THE Posrrion oF VACCINATION IN PaTHOLOGY AND
BACTERIOLOGY ;

BacTERIA AND BacrerroLocicAL MEtTHops7,AND
Draenosis

Non-BacteriaL Factors in Inrectious DisEAsEs

89

99

111
146

PREFACE

This publication is the outgrowth of work done for
the Indiana profession, having its origin in ‘a series of
papers upon the progress of bacteriology presented,
by request, to the State Medical Society between the
years 1890 and 1897.

These papers cover much of the time during which
the germ theory of disease was working its way into
the convictions of the profession, and it is with some
little pride that the author is enabled to feel that of
this progress he has been a part.

Presented under the special conditions indicated,
and in serial form, they have something of a historical
character and meaning which, even at the expense of
some repetitions, has been in large measure preserved.

To these have been added several, partly new,
partly prepared for the students of the Medical Col-
lege of Indiana or for various medica] gatherings.

6 PREFACE.

Those numbered from 2 to 8 in the Table of Contents
are given in the order of their preparation, covering
the years 1890 to 1896.

I am indebted to Dr. E. D. Clark and Dr. C. E.
Ferguson for aid in revising the manuscript, and to
Dr. A. W. Brayton for constant encouragement and
assistance in the preparation and arrangement of the
book.

Should the presentation of these essays in book
form be as kindly received by others as most of them
have already been by my friends, the doctors of In-
diana, it will be all that the author can ask.

INDIANAPOLIS,
February, 1898.

Essays on BactrerroLocy

I.
THE GERM THEORY OF DISEASE.

HE germ theory of disease, now no longer a the-

ory, but a demonstration of science, is a very sim-
ple doctrine. It asserts that certain disorders are due
to the presence and growth, in the body, of living
poisons called microbes, germs, bacteria, and that
without such bacteria these diseases do not exist.
Notice that certain disorders are said to have this
origin; for no one asserts or supposes that all diseases
are caused by bacteria. It is the maladies belonging
to the group called infectious which are due to living
agents, chief among which are the microscopic fungi
now commonly known as bacteria or germs. This
statement is a sufficient answer to the question, often
asked, whether we believe all diseases to be due to
microbes.

And here we notice two interesting and important
facts growing out of bacteriology. The first is that
the revelations of bacteriology have altered the classi-
fication of diseases, increasing the number of those
included among the infections. Thus, the discovery
of the germ of diphtheria has resulted in establishing

7

8 ESSAYS ON BACTERIOLOGY.

the fact that so-called membranous croup is usually
laryngeal diphtheria, and is therefore to be looked
upon as an infectious disease. A similar thing is true
of pneumonia, and notably of tuberculosis, over the
character and classification of which a controversy
was waged. We now know that tuberculosis is an
infectious disease; a half-century ago this was only
surmise.

We have learned, too, as a result of bacteriological
studies, more of the importance of infection as an in-
direct cause of suffering and death. Thus, while we
do not consider apoplexy an infectious disease, we
have come to see more and more clearly that, in the
last analysis, it is frequently a product of infection.
The blood vessels of the brain do not break unless
they are injured or diseased, and the disease which
thus makes a cerebral apoplexy possible is often of in-
fectious character or the indirect result of an infec-
tion. It matters not that this indirect result is some-
times seen only after many years: the fact remains,
and must constantly be borne in mind in practical
medicine. The man who falls by an apoplectic stroke
often falls from an infectious blow struck years be-
fore, perhaps when sowing the proverbial wild oats of
youth. And thus one may literally reap a harvest of
death from seeds sown and long since forgotten.

Thus we learn, notwithstanding the charge some-
times brought that the germ theory of disease is made
to account for too much, that its field of action is

ESSAYS ON BACTERIOLOGY. 9

really wider than is commonly supposed. As we look
about us and see the havoc wrought, directly and in-
directly, we may fairly say that it is hardly possible to
-exaggerate the importance of infection and of the
minute agents which produce it. The invisible ene-
mies are here, as elsewhere, the most numerous and
dangerous.

. The germ theory of disease is no new thing.
Though it has but recently come into prominence,
and its truth but recently been demonstrated, it is, as
a theory, as old, almost, as history. Crude, ill-de-
fined, and as crudely expressed, it has nevertheless
been for ages essentially the same. Hippocrates saw
and believed in it; and from his day to ours it has
served as a rallying cry for warring factions and for
the disputes of the learned. At times it has assumed
prominence, through the influence of some master
mind great in its capacity to grasp a simple and far-
reaching truth. Again it has sunk almost into obliv-
ion, carried down by the weight of its own artificially
and ignorantly imposed absurdities. Thus it has
risen and fallen, come and gone, with the varying tide
of speculative fashion. In this unstable but endur-
ing history there must be some reason, and for it we
have not far to look.

We can readily see why the germ theory of disease
so persistently suggested and asserted itself to men’s
minds. They saw many of the facts which we see.
They saw a small amount of poison enter the body of

10 ESSAY3 ON BACTERIOLOGY.

an animal or man, and afterward that the body con-
tained a much larger quantity of the poison. Thev
saw one case of a disease enter a community, and
afterward they saw, with strong evidence of transfer ~
from one to another, that many others had the disease.
From such facts they made the same inference as we
do. They said: these poisons seem to grow and mul-
tiply; they must be living; for such properties as true
growth and reproduction they, as we, only knew as be-
longing to living things. And this is the germ theory
of disease. When we inquire why this simple and
logical doctrine became, at times, contaminated with
so much absurdity as to bring it into merited discredit
and to even threaten its survival, the answer is not
difficult to find.

However rational, however logical, it was but a
theory, a mere speculation, shrouded in mystery. The
ignorant mind loves mystery, and all men love to
speculate about that which they cannot prove. We
all love to peer into the darkness, and where we can-
not see we quickly bring imagination into play. <A
Greek proverb tells us that the mysterious is always
great, and imaginary greatness is easily distorted into
absurdity. It is as true in medicine as in theology
that men often make the most positive and at the
same time most extravagant assertions about things of
which they know the least.

Thus the germ theory of disease became at times so
distorted, the subject of so many evidently unwar-

ESSAYS ON BACTERIOLOGY. 11

-

ranted embellishments, that honestly ignorant men re-
fused to believe it.

When we inquire why, aside from such abuses, this
rational and simple explanation of the infectious dis-
eases remained so long a mere theory, the answer, in
the light of present knowledge, is again not difficult.
“Knowledge is of things we see,” and there were no
means of seeing these minute objects which, with so
much reason, were supposed to exist. It was only
after the microscope, the aid to vision, was so far per-
fected as to enable men to look upon bacteria that it
could be demonstrated that such things really existed.
And only after many years of gradual improvement of
this wonderful instrument was this obstacle to prog-
ress overcome.

But to see bacteria in disease, even to prove by ob-
servation their constant presence, is not sufficient to
demonstrate their causative influence. It can at best
prove only that they are regularly associated with
abnormal processes in the body, and furnish strong
evidence that they are living beings. If now we will
go a step further and prove that they are actually the
seeds of disease, we must do what the agriculturist
does. We must be able to handle these seeds, to sep-
arate them from one another, to sort out the different
varieties, to obtain these varieties in sufficient quan-
tity for experiment; we must be able to plant them,
follow their growth, and find out what that growth
will produce. We must, in a word, cultivate these
our disease seeds as the agriculturist does his.

12 ESSAYS ON BACTERIOLOGY.

This now we are able to do. We can see bacteria,
can cultivate them, can identify and grow the differ-
ent varieties. We can plant them in the bodies of
men and animals, and reproduce at will the diseases
from which the bacteria were obtained. And thus
we are able to prove our theory. It is the invention
of methods for the artificial cultivation of bacteria
which has made it possible for us to handle and work
with these minute organisms, and which, with the aid
of the microscope, has removed the germ theory of
disease from the realm of speculation and established
it, as I have said, as a demonstration of science.

The germ theory of disease is no longer matter of
dispute. It is as clearly demonstrated as the laws of.
gravitation. Of him who does not know it it is to be
said that he has not as yet really heard the evidence
in the case. If anyone is still held in the bondage of
doubt, he has but to hear with an open ear this evi-
dence, and he will know the truth. And this truth
will make him free.

II.

SOME OF THE PROBLEMS OF BAC-
TERIOLOGY.

HERE is no subject which, during the last decade,
has occupied as large a partof the attention and in-
terest of the profession as the germ theory of disease.
It is perhaps safe to say that it would have been impos-
sible during the last few years to find a single issue of
any medical journal in Europe or America which did
not contain some reference to it. It is also safe to
say that the medical historian of the future will de-
scribe our age as chiefly characterized by the develop-
ments in this direction, and that, in the word picture,
the germ theory of disease will stand out pre-eminent.
When we consider the large proportion of suffering
and death due to the infectious diseases, medical and
surgical, and remember that this theory has offered an
explanation of their causation, propagation and many
of their phenomena, and points to methods not only of
eure, but of prevention, which is greater than cure,
we are not surprised that it should have risen rapidly
into prominence and already exercised such an influ-
ence in medical thought and action.

13

14 ESSAYS ON BACTERIOLOGY.

The rise of the germ theory of disease, as we now
know it, is one of those great movements—wide, deep
and far-reaching, such as are seen only now and then
in the progress of medicine, and which stamp the
character of its succeeding generations. It has modi-
fied and advanced our ideas of etiology; it has entered
the field of pathology and wrought great changes in
it, so that, for instance, we now say, in the language
of Strumpel: “The definition of tuberculosis has
now removed itself from a merely anatomical basis; it
is that disease which is called forth by the active
agency of the tubercle bacillus.” Dr. Senn has re-
cently expressed the opinion, the truth of which I
neither deny nor affirm, that “more real progress has
been made in surgical pathology during the last fif-
teen years than in twenty centuries preceding,” and
that “surgical pathology has become almost synony-
mous with surgical bacteriology.” Though to a lim-
ited extent, yet distinctly and helpfully, it has in-
creased our diagnostic abilities; it has added some-
thing to medical treatment, and has aroused, stimu-
lated, and guided many earnest efforts in this direc-
tion. It has strengthened the safeguards about the
puerperal woman, and so modified the methods of sur-
gery and emboldened its practice as to add much to
its efficiency. It has entered the broad realm of sani-
tary science and preventive medicine, and, throwing a
new ray of light toward that promised land, ‘has
brightened our hopes for the coming of a better day.

ESSAYS ON BACTERIOLOGY. 15

Bacteriology has passed the stage of curiosity and
sensation; it is not a scientific by-play nor a micro-
scopic diversion; it is a study of pathology and the
causation of disease, and as such has taken its place
among the branches of medical science and in the
curriculum of medical studies. We are all watching
it—interested in it, and now that it has become a
somewhat old story, must often ask ourselves: What
is it doing and what does it propose to do? What
problems are before it and how is it endeavoring to
solve these problems?

Laying aside mere details and technicalities, which,
after all, attract the intelligent mind the least, I have
thought it might be of interest to consider very briefly
some of those problems which have been engaging the
attention of workers in this line, problems arising in
the struggle to overcome obstacles to the further de-
velopment of the work, problems involved in the
effort to render practically valuable the results already
reached. Omitting some which are of much, perhaps
of equal, importance, I mention the following:

Questions of the susceptibility of animals to the in-
fectious diseases; the durability of infectious material;
of disinfection; the manner of dissemination of disease
germs; are all infectious diseases due to one specific
cause; the question of hereditary transmission.

Koch lays down four postulates which must be
satisfied before we can fully accept the causative re-
lation between a bacterium and a disease. The last

16 ESSAYS ON BACTERIOLOGY.

two of these refer to inoculation; and the inoculation
experiments are the final and crucial tests of bacteri-
ology, at least so far as the pathogenic character of
the organisms is concerned. But here’ a difficulty is
at once met. It is evidently impossible to inoculate
men with the supposed causes of such diseases ag
cholera, tuberculosis, typhoid, syphilis, anthrax and
glanders. Animals must therefore be used, and the
question must at once be answered: are animals sus-
ceptible to all the infectious diseases? This question
resolves itself into two: are they susceptible, and how
do the diseases manifest themselves? By what signs
‘and lesions may we know that an animal suffers from
or dies of a certain disease? Are we to expect the
same symptoms and lesions as are found in human
beings? If not, they must be studied out for animals
as they have been for man.

The susceptibility of animals to cértain infections
is easily recognized; for instance, to erysipelas, sup-
puration, tuberculosis, anthrax, glanders and others.
Some animals are apparently entirely refractory to
one or more diseases to which others are very sensitive.
Moreover, it is not sufficient merely to show that inoé-
ulation with pure cultures will kill an animal; it may
have died of a sapremia or septicemia, not of a specific
disease from which the organism was obtained. For
there are organisms which are not known to have a
constant causative relation to any specific disease,
which, nevertheless, will produce pronounced toxic
effects when inoculated.

ESSAYS ON BACTERIOLOGY. 17

To illustrate the difficulties in this matter: It was
at first found that feeding with cultures of the comma
bacillus of cholera would not injure animals. The
result was, great doubt and even ridicule thrown upon
it. Some skeptics even offered to swallow any quan-
tity themselves. These facts are fresh in the minds
of all. But the comma bacillus flourishes in an alka-
lie medium, and, following up this indication, it
was found that inoculation directly into the duodenum
gave very pronounced results. Finally, after wash-
ing the stomach, injecting a sterile alkaline solution,
lessening peristalsis by opium, and then feeding or in-
jecting through a tube, the comma bacilli show them-
selves any thing but the harmless beings once sup-
posed.

It is well known that an organism has been identi-
fied in connection with typhoid fever and is generally
supposed to be the cause of that disease. But it is
still uncertain. Koch himself has recently, I believe,
taken this position, that while the Koch-Eberth bacil-
lus is probably the specific germ, the final demonstra-
tion has not yet been reached. The reason of this
uncertainty is the unsatisfactory character of the in-
oculation experiments. For it is not yet known
whether animals are subject to this disease; they may
die from the artificial infection, but it is not certain
that a group of symptoms and lesions can be identified :
in them, constituting the specific disease: typhoid
fever.

2

18 ESSAYS ON BACTERIOLOGY.

This question, then, of the relation of animals to the
infectious diseases is evidently one of importance in
bacteriological investigations, and the uncertainties.
connected with it furnish an obstacle which is often
deplored. Obviously also, as the work progresses,
here must open fields for painstaking and interesting
research. Incidentally these researches may throw a
valuable light upon veterinary medicine.

Is each of the infectious diseases due to a single and
constant, a specific cause? From the evident uni-
formity in their phenomena, it is generally believed
that this is true; and, for most of them at least, the
supposition is in all probability correct. Yet there
are some facts which have seemed to throw doubt upon
this belief, and in its present condition bacteriology
cannot answer the question with absolute certainty.
Two organisms, for instance, have been identified in
connection with croupous pneumonia; that of Fried-
lander, and the Sternberg-Pasteur-Freenkel micrococ-
eus. It is claimed that by inoculation with each of
these a more or less typical exudative inflammation of
the lungs has been produced. But they do not satisfy
the postulates of Koch. Neither has been found con-
stantly in pneumonia, and both have been found un-
der other conditions. So true is this that Frankel has
called one of them the microbe of sputum septicemia
rather than of preumonia. A similar condition of
uncertainty exists in the bacteriology of diphtheria.

Such experimental results as these, even though

ESSAYS ON BACTERIOLOGY. 19

there still be much doubt about them, at least raise
the question whether some of the supposed infectious
diseases may not be due to more than one cause;
whether, to put it concretely, an acute, self-limited,
croupous inflammation of the lungs, such as charac-
terizes pneumonia, or such lesions as belong to diph-
theria, may not be produced by more than one agent.
Probably not; yet it must be said that recent bacterio-
logical work has opened the question and has left it
still open.

Allied to this is the interesting inquiry whether a
pathogenic micro-organism may, in different localities,
and under different conditions, produce apparently
different diseases. A. connection between erysipelas
and puerperal fever has long been suspected, and re-
cent research has strengthened this suspicion. Vari-
ous authorities have asserted, on the basis of experi-
ment, that the Fehleisen streptococcus of erysipelas
would produce puerperal fever, and that the strepto-
coccus often found in the latter disease would produce
erysipelas. Some believe, partly because of these
facts, and partly because of the close resemblance in
the organisms, that they are the same. Certain it
seems, however, that an organism which would pro-
duce erysipelas has a number of times been cultivated
from child-bed fever. ‘

The question of the durability of infectious ma-
terial is one which has long interested and often puz-
zled the profession. It is not strange that it should

20 ESSAYS ON BACTERIOLOGY.

have been almost constantly under discussion, for it
confronts us daily, as practicing physicians, and is of
great importance in the broader sphere of preventive
medicine. To illustrate: When may children re-
turn to school from a family in which an infectious
disease has been prevailing? If tuberculosis is an in-
fectious disease, how long does tuberculous matter re-
main dangerous?

It would not be at all true nor fair to say that all
our present knowledge on this subject has come from
bacteriology; far from it. Much of it is the result of
that painstaking observation and study which pre-
vailed in former days. But much is the product of
the last few years; and in this connection it is to be
noted that progress of late has been upon more defi-
nite lines. If the infectious diseases are due to living
things, this question resolves itself chiefly into a study

"of those organisms. A specific germ being identified,
the question, how long may the poison of this disease
continue as poison, becomes, how long may this germ
live? The investigation evidently centers at once
upon a more definite point. How long, then, may
bacteria live? The answer is: it depends upon certain
conditions; and it is the discovery of the germs them-
selves, and increasing knowledge of the conditions
upon which their life depends, which has brought us
closer to a solution of this problem.

The life and growth of bacteria depends upon the
soil on which they are placed, and the external influ-

ESSAYS ON BACTERIOLOGY. 21

ences to whigh they are subjected. Two groups of
factors have, therefore, been studied in the effort to
obtain more definite knowledge of the durability of
infectious material, that is, the tenacity of life of
micro-organisms. Elaborate investigations have been
made of the relation between various bacteria and the
media containing them, and thus has opened up a
large field for the study of the growth and durability
of bacteria in various food substances, in milk and in
water. Thus, in milk many find a congenial home;
in water some retain their vitality for a long time,
others soon disappear. But aside from culture soils,
certain conditions have much to do with the life-his-
tory of bacteria, the most important being tempera-
ture, moisture, and the presence or absence of air.
Some grow only at high temperatures, that is, at about
body-heat; others at a much lower point. Some re-
tain life in the absence of any notable amount of mois-
ture, others quickly die when dried. Some grow only
in the presence of air, others flourish without it, and
hence the division into aerobic and anaerobic bacteria.

Then, too, considerable study has been made of the
destiny of bacteria in the body after death. The re-
sults are not as yet very conclusive, but the weight of
evidence seems to be that many kinds of germs soon
disappear. Esmarch has recently gone over this
ground again, his conclusion being that just stated; an
inference being that graveyards are not as dangerous
as has been supposed.

22 ESSAYS ON BACTERIOLOGY.

Without following the details of this subject fur-
ther, it may be said that our ideas of the durability of
infectious material have become more definite, the
lines of investigation have been much more sharply
defined, additions of much practical value have been
made to our knowledge, and we have reason to expect
more light in the near future. To illustrate what has
been done: It has been shown that the gonorrheal
poison rapidly loses its virulence; after even a short
period of drying outside the body it can neither be
cultivated nor inoculated. On the other hand, the
ordinary pus germs have been found to be very ten-
acious of life. Rosenbach, to whom we owe most of
our knowledge of them, has found them active after
two years in a culture tube.

But far and away beyond anything in this line is
the discovery that the essential infecting agent in tu-
berculous material may maintain its vitality for
months, even in a dried state, and not only its vitality,
but also its malevolent infectious character. Upon
this fact is based one of the most important discussions
which is at present agitating the medical and sanitary
world.

Closely connected with this problem of the durabil-
ity of infectious material is the question: How and
by what channels is it carried? Here, again, a large
part of our knowledge antedates bacteriology. But
the older methods were difficult, slow, and often un-
certain, and not infrequently, while furnishing most

ESSAYS ON BACTERIOLOGY. 23

valuable facts, left them without satisfactory explana-
tion. I have already emphasized the fact that bac-
teriology has placed this and kindred investigations
upon a more secure foundation; has laid down the
lines more sharply, and given to means and methods a
more definite aim. How this is true must be evident.
A definite material thing having become known as
the essential infecting agent, the methods of its identi-
fication, its life-history and the conditions of its dura-
bility established, we at once know what to search for
in the endeavor to trace the poison from place to place
or person to person. Thus earth, air, water, foods,
hands, instruments, fomites of various kinds, are made
to vield their secrets, and are known as, not hypothet-
ical, but proven carriers of disease. To draw illustra-
tion again from the great scourge: If it be shown
that the tubercle bacillus is the sinning agent in the
tuberculous material, that it exists in the products of
the lesions, that it retains its vitality through long peri-
ods under apparently adverse conditions, that it can
be detected in its hiding places outside the body, and,
with virulence unchanged, can be traced through
milk, clothing, furniture, floors and dust; if these
things are true, is it to be wondered at that they have
modified the older opinions, and are leading many to
believe that we have come nearer to a solution of one
of the medical riddles of the ages?

Among all the subjects which might be brought
under the title of this paper there is, perhaps, nothing

» 24 ESSAYS ON BACTERIOLOGY.

more striking than the contrast between disinfection
-before and since the recent growth of bacteriology.
Heretofore it has been in some respects almost like
beating the air or fighting in the dark. Now the gen-
eral problem of disinfection has reduced itself to this:
How most efficiently and with least danger to insure
the destruction of disease germs. The second condi-
tion is important because many germicidal agents are
active poisons.

Definite knowledge having been reached as to just
what is to be destroyed, experimenters are at once
able to drive at the heart of the first problem of disin-
fection: What agents will destroy these bacteria,
and what is their relative germicidal power? As the
result of these studies, bi-chloride of mercury stands
at the head of chemical agents, heat of the non-chem-
ical; and perhaps the most important result of the in-
vestigation of disinfectants is the high place given to
heat, not only in theory but in practice.

Another interesting and important set of facts has
been brought out, as the result of which disinfectants
have been classified, as to their activity, as follows:
First, those which rapidly destroy both bacteria and
spores; second, those which destroy mature bacteria
but not spores; third, those which prevent the devel-
opment of bacteria or spores, and, finally, those which
more or less retard their development. It will at once
be seen that this classification is of more than theoret-
ical interest. For, as is well known, many if not all of

ESSAYS ON BACTERIOLOGY. 25

the-chemical germicides are poisons. Their use there-
fore to the point of destruction of the bacteria might
also result in destruction of the host. Obstetricians
have learned this by some bitter experiences. It is
therefore a matter of very practical value to know that.
below the point of lethal strength these agents may
prevent, or so far retard the growth of bacteria as to
make their action truly disinfectant. It is well to re-
member this, that it is not an irrational nor a useless
thing to use weak solutions of disinfectants.

Another point which has been made clear is, that
the relative practical value of these agents is not the
same as their relative germicidal power, and that the
strongest germicide is not necessarily always the best
to use. This fact rests not solely upon the poisonous
quality of some of the chemical disinfectants, but
upon other grounds also. Thus, the bi-chloride of
mercury, in the presence of albumen, is thrown down
‘as an insoluble albumenate. ‘This everyone has seen
in dressing a bleeding wound. Solutions of this sub-
stance, even when made with ordinary distilled water
of the shops, may be much weaker than their users
innocently believe. Hence, the plan of adding such
agents as ammonium chloride or tartaric acid to pre-
vent this change. Other things of minor importance
are also to be taken into account in deciding the ques-
tion of the practical utility of germicides, as their irri-
tant, corrosive, or staining properties, their cost, odor,
solubility, ete.

26 ESSAYS a BACTERIOLOGY.
a
en,

When we come to consider the question of disinfec-
tion of such substances as clothing, bedding, sputa
and feces, it is evident that we are in a much better
position to do effective work than our predecessors.
We no longer confound deodorants and disinfectants.
Every one who has read “The Innocents Abroad” will
remember the picture of the unfortunate passengers,
just landed from their ship, undergoing the horrible
and probably quite useless fumigation. There is
more than a suspicion that the deodorant properties of
the sulphur were mistaken for disinfectant virtues.
We smile at it now, but it was an honest effort.

Do we wish to know how best to disinfect a bale of
rags from Italy? The bacteriological test is compara-
tively simple and certain. What method will render
tuberculous sputum harmless? The test is the same.
Will we learn how to purify the materials from a sick
room? Look for the effect upon the agents of infec-
tion. The verdict over the pestiferous intruders:
“Dead, for a ducat, dead,” is worth more than all the
odors which sulphurous compounds can emit.

The intimate relation between bacteriology and the
question of the hereditary transmission of disease be-
comes at once evident if the truth of the recent ideas
as to the cause of the infectious diseases be, admitted.
If bacteria are the sole exciting cause of certain dis-
eases, if these maladies cannot exist without their
agency, then the hereditary transmission of such dis-
eases means the transmission from parent to offspring

ESSAYS ON BACTERIOLOGY. 27

of these bacteria. This by no means rules out the ex-
istence and importance of predisposing causes, but it
brings the chief and most direct factor into the fore-
ground, and limits the investigation to a narrower,
more definite and more pointed question.

Do bacteria or their spores pass from parent to off-
spring with the beginning of or during intra-uterine
life? Does the fetus emerge from its mother’s uterus
with the germs in its body? The light on this ques-
tion of heredity has heretofore come chiefly from a
clinical rather than a pathological source. An im-
mense mass of clinical facts has been gathered, but
has not sufficed to settle the whole matter. Notably
is this uncertainty true of tuberculosis, that disease in
connection with which the study of heredity is of such
importance. Many cases have been recorded which
seem to prove that certain infectious diseases may be
transmitted to the fetus, as smallpox and measles.
Further, it seems to have been shown that the bacilli
of anthrax may pass from the mother to the young in
utero. We have, then, apparent proof of hereditary
transmission of an infectious disease whose bacteria, if
such exist, are not known, and of one with whose bac-
teria we are thoroughly acquainted. It seems, there-
fore, not unreasonable to suppose, the supposition be-
ing strengthened by the well-known clinical facts,
that such a disease as tuberculosis may be acquired
before birth. Parties are divided on this question,
some holding the opinion expressed by Whittaker,

28 ESSAYS ON BACTERIOLOGY.

that the supposed hereditary acquisition of tubercu-
losis resolves itself into the results of association of
cases, in other words, post-natal infection. Others
hold to the view which commonly prevails; while
some endeavor to explain the facts upon the theory, of
which Baumgarten is the chief exponent, that the
bacilli received by heredity often remain latent for
months or years, springing into activity with the rise
of conditions favorable to their growth. Evidently,
more light must be obtained before the problem can
be solved, and bacteriology has stepped in with an
offer of aid; first, by showing what is the actual cause
of the disease, and leading in the search for this defi-
nite material thing in the body of the fetus. The
greatest interest has centered around tuberculosis, for
obvious reasons.

I do not propose to enter here into elaborate details,
but simply to indicate the lines along which the inves-
tigations have run. The search has been made by
microscopic examinations, by cultivations, and by in~
oculation experiments. Thus, a number of female
animals are inoculated with tuberculosis. They are
bred, if not already pregnant. Only the fetuses of
such mothers as can be proven to have the disease are
used. Their bodies being carefully protected from
contamination, the following experiments are made
upon them: They are examined microscopically, cul-
tures are made from them and portions of their bodies.
are inoculated into healthy animals. The cultures

ESSAYS ON BACTERIOLOGY. 29

and inoculations are made in order that if the bacteria
should escape ocular detection they may still be
found. On the strength of these researches some
have claimed to prove the passage of the germs to the
fetus, while some, conducting their studies with every
precaution, have reached only negative results, and
have believed that the apparent exceptions in the
hands of others were, due to contamination. A report
made to the Paris Academy about a year ago was en-
tirely negative, and this has been the rule. The well-
known case of Johne, who proved fetal tuberculosis
in a calf, stands alone unquestioned.

The end has not yet been reached. There are still
claims and counter-claims, strong beliefs and influen-
tial skepticism. Certainly some of the infectious dis-
eases seem to be transmitted by heredity, or at least to
be congenital. As regards tuberculosis, there has
been an unmistakable growth of the opinion that the
disease is to be looked upon as an infection, not an in-
heritance; that the ideas of its heredity have been
much exaggerated; that it is comparatively rarely
transmitted to the fetus—perhaps never. How much
of the hopes of preventive medicine depend upon the
truth of these opinions is at once apparent. Whether
we shall fail to reach positive knowledge, and, opinion
wavering, the pendulum shall swing again toward its
former position, remains to be seen. In the mean-
time let us get a clear view of the facts already estab-
lished, give due credit and appreciation to the sincere
and earnest efforts for the solution of the great ques-

30 ESSAYS ON BACTERIOLOGY.

tion, and, as practicing physicians, not forget the facts
of clinical experience.

I have not in this paper discussed nor raised the
question of the truth or falsity of the germ theory of
disease, nor entered further than was necessary into
the details and technicalities of bacteriology. I have
purposely avoided these things in order that I might
insist upon the idea that they are of secondary inter-
est. Bacteriology is a study of pathology and the
causation of disease, and of the problems which gather
about these two great fields in medicine. It is only
as we thus think of it that we shall be able to under-
stand what it is and what it means.

Though we are, and must be first of all, practition-
ers of medicine, it is well for us now and then to stop.
and think what some of these things mean and where
we stand upon some of the great problems which are
arising in our profession; to think whence we have
come, aud why, and whither we are going. Surely,
if we preserve our balance aright, it need not make us
less efficient actors if we keep ourselves somewhat in
touch with the world of theory and of thought.

If this discussion shall have succeeded in some de-
gree in throwing the laboratory, the microscope and
the mere details of bacteriology into the background,
and in placing in deserved prominence some of those
living problems which should most interest the intelli-
gent physician, should attract his attention, enlist his
sympathy and engage his thought, its object will have
been accomplished.

III.

SPECIFIC DISEASES AND SPECIFIC
BACTERIA.

S practicing physicians we are always interested

in the question: What is the status of our knowl- -
edge of.the relation. between individual diseases and
specific bacteria? In other words: What do we now
know of the specific causes of the infectious diseases?

It is not my intention to review the whole field, but
confining myself to the more important diseases which
affect mankind, to endeavor to answer the question:
What do we know of their germ origin?

It cannot be said that any striking discoveries of
new disease-producing germs have been made of late;
but much has been done in solving some vexed ques-
tions and in clearing up some uncertain points.

During the first few years after the new methods
had come into use, and under the stimulus of the
epoch-making work of Koch and Pasteur, discoveries.
came thick and fast. Indeed, it almost seemed as
though one could not gain repute in bacteriology
without first having attached his name to some new
germ. Of late years progress in this line has been

31

382 ESSAYS ON BACTERIOLOGY.

slower, the discovery of new bacteria has become
of less importance. The germ-theory of disease has
been absolutely established, the specific germs of cer-
tain infectious diseases have apparently been settled,
and there is a general agreement as to the probable
bacterial origin of the others whose specific germs are
not yet known. The grounds for this belief are well
understood and need not be reviewed here.

The question is often asked why the bacteria of cer-
tain diseases, as measles and scarlatina, which are com-

-mon enough and are evidently infectious, have not
been discovered. There is, of coutse, every reason to
believe that these maladies are due to living poisons,
and it does seem strange that they have thus far
baffled investigation. The more strange does it seem
at first sight, in view of the fact that the methods of
bacteriological research are now so well understood
and the cultivation of many germs so comparatively
easy.

There are, however, some marked differences be-
tween the poisons of measles, scarlatina, smallpox,
and many other infectious diseases. For instance,
they are apparently much more readily disseminated
through the air; they are said to be more “volatile.”
The opinion, therefore, has grown that these differ-
ences are indicators of others more profound, and
which make it impossible to cultivate them by the or-
dinary methods. Until, therefore, further progress
has been made and perhaps radically new methods in-

ESSAYS ON BACTERIOLOGY. 83

troduced, it is possible that the bacteria of these dis-
eases may remain in obscurity. There are other diffi-
culties in the way of the investigations, some of which
have already been explained. The problems are not
as simple and easy of solution as some suppose; and we
could hardly expect that, in the few years since mod-
ern bacteriology arose, the field would have been
swept clean and there remain no more undiscovered
territory.

Turning now from this explanation, let us review
briefly our knowledge of the specific bacterial causes
of the infectious diseases, remembering that with some
the demonstration seems to be complete, with others
only a high degree of probability has been reached;
with many there is still a large element of uncer-
tainty.

In making this summary I shall omit such facts as
are already commonly known, and shall divide the dis-
eases into several classes:

First. Those of which it may be said that the ques-
tion of their bacterial origin is apparently settled. It
will, perhaps, be surprising to some that so few are in-
cluded in this class. They are anthrax, tuberculosis,
glanders, suppuration, tetanus, erysipelas. Probably
more increase in knowledge has of late come in regard
to tetanus than any other of the diseases included in
this group. The mystery in regard to this grave af-
fection has apparently been cleared up. Kitasato has
succeeded in perfecting a method of producing pure

3

84 ESSAYS ON BACTERIOLOGY.

cultures, and by repeatedly successful inoculation ex-
periments removed all doubt as to the fons et origo
mali. The tetanus bacillus is a large rod, rounded at
the ends, sometimes growing to long threads. It is
motile, grows at ordinary temperature, and is strictly
anaerobic—i. e., it does not grow in contact with the
oxygen of the air. It stains easily by the ordinary
methods. It is found in garden mould, on walls, in
putrefying fluids, in manure, and in places frequented
by horses. ‘The association of tetanus bacilli with the
earth and with horses has been strongly insisted on by
a number of investigators. It is a striking fact that
the bacilli are not found distributed through the body
after death, and that their number at the point of in-
fection is not proportional to the severity of the symp-
toms. This is explained by the discovery that the
bacilli give rise to a most virulent poison, which, freed
from germs, is capable of producing death with all the
symptoms of the disease. The anaerobic quality of
the germ probably explains the fact that penetrating
wounds are especially liable to be followed by tetanus.

As to erysipelas, authorities are agreed that the
same germ causes both traumatic and so-called idio-
pathic erysipelas. The sharp line hitherto drawn be-
tween these varieties of the disease should therefore
be removed.

In regard to the bacilli of tuberculosis, some inter-
esting investigations have been made in several direc-
tions.

ESSAYS ON BACTERIOLOGY. 35:

First. It seems to have been shown by Ernst and
others that the bacilli may be present and living in the
milk of cows whose udders are not tuberculous. The
importance of this fact will at once be recognized.

Second. A series of experiments has been carried
out to decide whether the bacilli could penetrate the
apparently healthy mucous membrane. The result is
the conclusion that they can, together with the discov-
ery that they are, under such circumstances, likely to
be caught in the nearest lymph glands, and may pro-
duce the phenomena of ordinary tuberculous adenitis.
These investigations are held to throw light upon the
character of so-called scrofula.

Third. The immensely important question of Ia-
tent tuberculosis appears to be nearing a solution, in-
asmuch as it has been shown that the bronchial and
other glands of apparently healthy persons may con-
tain living tubercle bacilli, and this, too, in the ab-
sence of any visible tuberculous lesions. H. P.
Loomis has recently recorded a series of autopsies, con-
firming this statement. If it be shown that long la-’
tent tuberculosis may exist in the body, or that bacilli
may remain in the body through long periods without
producing the disease, it will at once be seen how this.
fact will explain many things in the clinical history of
the disease, and how it may throw light on the still
vexed question of hereditary transmission. As to the
hereditary transmission of tuberculosis, the investiga-
tions are still going on, but a certain conclusion has

36 ESSAYS ON BACTERIOLOGY.

not been reached. The establishment of the possibil-
ity of bacilli remaining long inactive in the body has
given the advocates of heredity, of whom Baumgarten
is the leader, a firmer ground for their belief. In
addition to the case of Johne, a few more of hered-
itary transmission in animals have been recorded, and,
it is claimed, one in man. Were I asked to express
an opinion upon this matter, I would almost repeat my
former words: that there is a growing belief that the
older ideas of heredity are exaggerated; that the dis-
ease is to be looked upon as an infection rather than
an inheritance; that it is comparatively rarely trans-
mitted from parent to child in utero; adding, how-
ever, the opinion that the doctrine of heredity is as
yet by no means overthrown. We must still wait for
the whole truth.

In the second group of diseases I include those
whose bacterial cause has in all probability, but not
absolutely, been established. These are leprosy, chol-
era, typhoid, relapsing fever, pneumonia, diphtheria,
gonorrhea.

It is doubtful whether the leprosy bacilli have ever
been successfully cultivated, but transplantation of
leprous tissue containing them has repeatedly been
followed by a reproduction of the bacilli and the dis-
ease. Nor have the spirilla of relapsing fever been ob-
tained by artificial culture. They are, however, al-
ways present in the blood in the disease, and success-
ful inoculation is always followed by their appearance

ESSAYS ON BACTERIOLOGY. 37

in the new victim. The micrococci of gonorrhea
have been artificially cultivated in only a few in-
stances; the procedure is very difficult, and the cul-
tures soon die. A few successful inoculation experi-
ments have been made upon men, but we should like
to see a larger measure of proof before we lay aside all
doubt. Certain it is, however, that the remaining
doubt is very slight.

As to cholera, there is but a shadow of uncertainty
remaining that the comma bacilli of Koch are the
specific cause of the disease. Whatever uncertainty
there is, is due to the lack of inoculation experiments
upon man. One accidental case has probably settled
the matter, but one case is hardly sufficient. In all
other respects the evidence is complete. There has
been discovered a rapid method of identifying cholera
cultures by the production of a violet-red or purplish-
red color upon the addition of pure sulphuric acid.
This method may be of great value for the purpose of
quick diagnosis in a given case.

The Koch-Eberth typhoid bacillus remains about
where it was. It is, in all probability, the specific
germ, but in the absence of the final test, i. e., inocu-
lations, some uncertainty remains. Vaughan is skep-
tical in regard to this bacillus, believing that typhoid
may be due to more than one cause; in other words,
that it is not a specific disease. Certainly most au-
thorities do not agree with this view.

Of diphtheria, it seems to be about settled that the

38 ESSAYS ON BACTERIOLOGY.

bacillus of Loeffler is the specific germ, and that there
is but one cause of genuine diphtheria. The recent
researches of Welch and Abbott in Baltimore have
confirmed this view. It is, however, possible that a
pseudo-membranous disease may be excited by other
agents than the diphtheria bacillus, and Prudden
wisely suggests that it is not best to close the discussion
until all the evidence is in.

As to the germs of pneumonia:. The pneumococ-
cus, or pneumo-bacillus, of Friedlander has about lost
its significance. Of it Frenkel says: ‘Neither mi-
croscopic investigation, nor culture, nor transmission
having furnished sufficient proofs for the assertion
that the pneumococci play a decided role in the origin
of pneumonia, we cannot recognize them as the causal
factors of this disease.” He adds: “It may, there-
fore, be assumed that they are at any rate related to
the said affection, and it may not be amiss to regard
them (like the streptococci in typhoid) as subsequent
settlers on a soil prepared and properly fitted by the
activity of some other micro-organisms.”

The pneumococcus of A. Frenkel, on the other
hand, which, it will be remembered, was first discov-
ered by Sternberg, has risen immensely in importance.
Of it I cannot do better than quote again the words of
Carl Frenkel. “Tt belongs,’ he says, “to the most
virulent of infectious micro-organisms known. It is
proved to exist in over 90 per cent. of all cases of
pneumonia. The fact of its being missed here and

ESSAYS ON BACTERIOLOGY. 39

there is not difficult to account for, when it is remem-
bered that it cannot be surely recognized by micro-
scopic examination alone, and certain difficulties in its
cultivation are not always sufficiently heeded by all
observers.”

Freenkel’s bacteria are by no means exclusively
found in pneumonia. They are found in almost all
cases of cerebro-spinal meningitis, and the origin of
this affection is reasonably attributed to them. <A.
Frenkel has found them in pleuritis, Weichselbaum
in peritonitis, Banti in pericarditis, others have en-
countered them in endocarditis and otitis media and
numerous other affections. They occur especially in
the saliva and nasal secretions of healthy persons, as
established by Netter, and they may be regarded al-
most as regular tenants of these localities. Freenkel’s
diplococeus is indeed not the exciter of pneumonia
alone; its domain is more extensive; it does not restrict
itself to this one function.

Freenkel’s bacterium is perhaps the principal ex-
citer of inflammatory processes of an infectious nature
in the human body. Wherever it reaches a serous or
mucous membrane and meets with the requirements
for its settlement, it commences operations. It causes
meningitis on the pia mater, peritonitis on the peri-
toneum, and otitis in the auditory passage. When-
ever it gains entrance into the lungs, pneumonia is de-
veloped, the peculiar properties and characteristic pro-
cedure of which depend upon the peculiarities of the

40 ESSAYS ON BACTERIOLOGY.

organ invaded and upon the extent of the morbid
process. Another bacterium may eventually play a
similar role and give rise to pneumonia, but, as a rule,
it is certainly Freenkel’s diplococcus that displays here
its energy, for which reason it may properly be re-
garded as the real micro-organism of genuine croup-
ous lung inflammation.

But how can this view be harmonized with the cir-
cumstance that this micro-organism is also a frequent
guest in the healthy body; that in the majority of all
persons it is domesticated in the mouth, whence it
might easily and at all times undertake an excursion
into other regions and thus soon produce meningitis,
otitis, or something else? Does the “sword of Damo-
cles” actually hang at every moment so close to our
heads, and must it not appear almost miraculous that
anybody at all is spared by this terrible foe? We can
account for this certainly very striking fact only by
the circumstance that it requires, as a rule, certain
preparatory, as yet unknown, factors to enable this
bacterium to make its attacks. The healthy cover-
ings and tissues of the body resist the micro-organ-
isms; only when the native powers of resistance are
weakened or neutralized do the foreign invaders take
a firm footing and begin their pernicious activity. All
the minute gradations of their infectious power (ob-
served even under the conditions of their natural ap-
pearance, and surely strong enough to determine the

ESSAYS ON BACTERIOLOGY. At

severity of a single case or the character of an epi-
demic,) will find their explanations in this hypothesis.

Reference ought here to be made to at least one
other disease, namely, malaria. It is well known that
there has been found a peculiar body in the blood of
those suffering from this malady, called after its dis-
coverer the plasmodium of Laveran. It is described
as a low organism, not belonging to the class of bac-
teria, but to the animal kingdom, to be included
among the protozoa or mycetozoa, and for this reason
named plasmodium. It is found within the red cor-
puscles. The organism is small, round or irregular,
having a rapid ameeboid movement; it grows rapidly,
soon fills the larger part of the corpuscle, and before
long is found to contain many roundish granules or
rods consisting of black pigment. It is easily recog-
nized, stained or unstained, in the blood freshly taken
from the finger during the attack. It has never been
artificially cultivated. Inoculation experiments are
therefore wanting. But by agreement among many
investigators in Europe and America, it is of great
value in diagnosis, enabling us to distinguish with cer-
tainty between malaria and other fevers. This fact
at once makes it of much practical interest.

Another important matter is now arising in the field
of bacteriology. The germ theory of disease is set-
tled; it has become an established fact. But what
does it mean and whither is it leading us?’ Why these

42 ESSAYS ON BACTERIOLOGY.

reachings out into such experiments as the Koch
treatment of tuberculosis, the preventive inoculation
against rabies, tetanus and diphtheria? We are ap-
proaching the pressing question of immunity, and,
for practical medicine, the greatest problem of our
day: Can we, and how best shall we, combine science
and art to confer upon humanity the inestimable boon
of immunity or cure, or both cure of and immunity
from the infectious diseases?

IV.

SELF-LIMITATION AND IMMUNITY
IN DISEASE.

REAT questions are arising among us as the out-
growthof bacteriology, the most important ques-
tions, probably, with which modern medicine has to
deal; namely, those concerning self-limitation of and
immunity from the infectious diseases. This is the di-
rection in which all eyes are turned, and this is the
direction in which we hope to see the triumphs of
medicine in the near future. This I say, of course,
with the understanding that the broad preventive
measures belonging to sanitary sciemce are not under
present consideration.
_ It was not long after the discovery of specific path-
ogenic bacteria that the question began to be raised:
How do these minute organisms produce their effects?
Nor was it long before it had been clearly shown that
the harm was not done by the mere presence of micro-
organisms in the body; in other words, that a mechan-
ical explanation was not sufficient save in a very lim-
ited and exceptional way. Almost equally untenable
was the theory that the bacteria,, in their growth,

43

44 ESSAYS ON BACTERIOLOGY.

robbed the body of important substances, to the detri-
ment of the host. Already it had been shown that
the new substances arising in the course of the fer-
mentations were the results of the activity of minute
living organisms. The yeast is put into the batter; it
grows, reproducing itself, spreads through the whole,
produces carbonic dioxide and alcohol, and the dough
is inflated—made light. Here, then, is proof positive
that a small amount of matter may, as the result of its.
possessing the properties of living things, spread
through a large mass, bringing about marked chem-
ical and gross physical changes, the latter being due
to the new chemical bodies formed in the process.

So far as the facts were known, the analogy be-
tween the fermentations and the infectious diseases
was exact. A small quantity of the poison of anthrax
being introduced into the body of an animal, or may
in some mysterious way multiplies, spreads through
the body, and profoundly modifies it. This poison
must be a living thing. Yes, it is proven to be such,
and is definitely identified. May not the analogy go
further, so that we may say that the modifications are
due chiefly to new chemical substances, just as in the
fermentations?

That the bacteria do, in the course and as a result
of their growth, bring about the formation of new
products, and that, in many instances, these are ex-
tremely poisonous, is now established, and this knowl-
edge we owe chiefly to the labors of Brieger. The

ESSAYS ON BACTERIOLOGY. 45

establishment of this fact at once quickened research
upon the question whether these new products were
not the efficient agents in bringing about the multi-
form and striking effects of infection.

In order to solve the problem, it was necessary to
secure the material for experiments free from living
germs, and for this purpose two processes have been
used, the bacteria under question having been ob-
tained artificially in pure culture. In the first proc-
ess the cultures were subjected to heat sufficient to
kill the micro-organisms. But it was ascertained that
the heat might also destroy the delicate substances
whose action it was desired to investigate. Recourse
was therefore had to the process of filtration, devised
by Pasteur and Chamberland, and this, or some modi-
fication of it, is now generally recognized as the most
reliable method, inasmuch as nothing is destroyed or
changed, the bacteria are removed, and presumably
all of the desired products are secured. Some of
these substances have also been isolated, by definite
chemical processes, from the infected body or from
cultures. Brieger has been the leader in this work,
but thus far it is confessedly difficult, and has yielded
only incomplete results, since bacterial growth is, as a
rule, attended by the formation of several so-called
ptomaines or toxins.

Though the work is beset with difficulties and com-
plications, enough has been established to warrant the
conclusion that the phenomena following infection are

46 “E3SAYS ON BACTERIOLOGY.

largely, if not entirely, due to the action of new prod-
ucts formed in the growth and multiplication of the
bacteria, and that the peculiar phenomena belonging
to the specific diseases and constituting their specificity
are chiefly, if not wholly, due to the peculiar proper-
ties of the ptomaines formed by their specific germs.
Of these phenomena we have now to consider those
two which are of greatest interest to us in our contest
with the infectious diseases, namely, self-limitation
and immunity.

From time immemorial it has been known that
there. was a group of diseases which were distinctly
self-limited; they did not run an indefinite course;
they ended of themselves. As the old saying is: “If
the patient lived long enough he would recover from
that disease.” To this class of maladies belong
measles, scarlatina, diphtheria, erysipelas, and others.
Here was a great mystery. What was the explana-
tion of it? Theories have been advanced, only to be
disproved or discarded. Those which have not been
disproved have been discarded or held in reserve be-
cause there was no way of testing their truth or falsity.

With the rise of modern bacteriology the hope be-
gan to be entertained that we might now come nearer
to the solution of the problem. Here again the anal-
ogy between the fermentations and the infectious dis-
eases threw a light along the way, indicating the di-
rection for the investigation to proceed. It is known
of certain fermentations not only that they are accom-

ESSAYS ON BACTERIOLOGY. 47

_ , panied by the formation of new chemical bodies, but
that through the agency of these substances the fer-
mentation is stopped. In a word, the process is self-
limiting; the ferment is drowned, or benumbed, in its
‘own products. Some of these bodies are known; they
are recognizable by ordinary chemical methods, and
by their use we may imitate, artificially and exactly,
the natural self-limitation of the processes by which
they are produced. All this is true of the ordinary
alcoholic fermentation.

Of course, the question arose whether something of
the same kind might not explain the phenomena of
the self-limited diseases. Might it not be that the
new compounds resulting from the growth of the
germs in the body, either by altering the soil on which
they grow or actually poisoning them, bring the dis-
ease to an end, and thus be explained one of the great-
est direct life-saving agencies known to man? Cer-
tainly the analogy from the fermentation would seem
to warrant the inference which experiments, so far
made, tend only to confirm. It might be said that
the apparent self-limitation is no real self-limitation,
but only a subsidence of the disease accompanying the
completion of the cycle of the germ’s natural life-
history. But such an explanation is untenable, for
there is no such cycle of life-history in the sense just
indicated. Given the proper conditions and suitable
food, and the germs will continue to multiply and re-
produce themselves indefinitely. Nor is the theory

48 ESSAYS ON BACTERIOLOGY.

of the exhaustion of the available food-supply any
more tenable. It is sufficiently disproved by the fact
that in some diseases, which are distinctly self-limited,
as tetanus, diphtheria and erysipelas, the germ growth
is confined to a small spot in the body. And yet in
ease of diseases in which one attack does not afford
protection against others, the same germs may, soon
after the first attack, be successfully implanted in an-
other part of the body, and the same phenomena of
self-limitation of the disease be seen. The proper
food is evidently not exhausted.

Why do not the germs continue to grow indefinitely
in the body? Why do they die out with such regu-
larity? Apparently but one explanation remains.
There must be some actual interference with their
further growth, either in a temporary or permanent
modification of the tissues, which renders them unfit
for the sustenance of that special germ, or in an agent
which directly antagonizes or even kills it. This is
the belief which is now generally and with good rea-
son entertained, and upon it are based the most active
and perhaps most promising efforts to attack the cause
of the infectious diseases even after they have invaded
the body.

But there is another fact, long known, concerning
certain of the infectious diseases, equally astonishing
and life-saving as self-limitation, namely, self-protec-
tion, or immunity. It is true of some of these mal-
adies that one attack protects against others; the body,

- ESSAYS ON BACTERIOLOGY. 49

if haply it survives the first, is endowed with an im-
munity from subsequent infection by the same germ.

Here. is a phenomenon quite different from self-
limitation, and requiring, perhaps, a different explana-
tion, for they are by no means commensurate, nor
even co-existent in the history of a disease. The one
may be present, the other absent; one may be strongly
marked, the other moderate, or but very slight. Ap-
parently, therefore, they do not necessarily depend
upon one or the same cause; indeed, there is reason to
believe that, in some diseases, at least, they result
from quite different causes, and are brought about in
different ways.

Can we explain immunity, or, if not, can we dis-
cover and imitate the process by which it is estab-
lished? Here, too, theory has run riot in the field
where knowledge was wanting, but a satisfactory con-
clusion has not yet been reached. Of these theories
the following are worthy of mention: First, that of
‘exhaustion; that the growth of the germs exhausts the
nutritive substances necessary for their life, thus leav-
ing the body incapable of supporting the germs in the
future. This explanation is now believed to be un-
tenable, for reasons previously stated. Second, the
theory of retention; that some peculiar substance is
left in the body which antagonizes the germs should
they subsequently enter. Of this Frenkel says it is
possible, though not probable, and may be retained as
a working hypothesis. Third, the phagocytosis the-

4

50 ESSAYS ON BACTERIOLOGY.

ory of Metschnikoff, which explains immunity thus:
that the cells, especially the leucocytes, have conferred
upon them, as the result of the first attack, the special.
property of subsequently devouring and destroying
the same germs. Fourth, the theory of the germi-
cidal power of the blood serum. It is known that
certain animals are naturally unsusceptible to certain
diseases, and that the introduction of their blood se-
rum into susceptible animals may confer upon them a
more or less lasting power of resisting those germs to
which the first animal was naturally immune. This
is the theory upon which was based the goat blood and
dog blood treatment of tuberculosis.

Of these theories Frenkel observes that there is
probably a truth in all, and that artificial immunity is
not acquired by one regular process, but sometimes in
this manner, sometimes in that, and that it is quite
possible and even probable that causes are at~work
which are as yet unknown, and which future investi-
gators are destined to discover. But whatever the
manner of action, the primary fact remains that in
certain diseases the growth of the germs in the body
leaves it protected against a subsequent invasion of
the same germ; and further, that this acquired im-
munity is brought about through the agency of the
new chemical bodies evolved during the germ growth.

Naturally, the knowledge of these facts has given
rise to an extensive series of experiments, all having
for their object the imitation of nature in securing

ESSAYS ON BACTERIOLOGY. bt

immunity. This work has not been without striking

results. There are several diseases, such as anthrax, .
symptomatic anthrax, swine erysipelas, and, perhaps,

tetanus, rabies and diphtheria, the attack upon which

has shown an encouraging degree of success.

It will be seen that, as a practical matter, the imi-
tation of natural self-limitation and immunity, that is,
cutting short or curing, and protecting against infec-
tion, present quite different problems.

Here rises into prominence another matter. As al-
ready stated, bacterial growth is often or usually ac-
companied -by the formation of several new com-
pounds. Which of these is the effective agent in the
self-limitation, and which in affording immunity? Are
the substances which do the harm and render the dis-
ease dangerous the same as those which do the good?
This is a question of great importance, especially when
we come to the problem of imitating self-limitation
and thereby cutting short and curing a disease. If
the harmful and helpful agents are the same, it is open
to question whether we may legitimately introduce
into a body already suffering under an active disease
an agent which, while re-enforcing the tendency to
self-cure, may also increase the tendency to death.
Under these conditions it would seem that such treat-
ment could, at best, be of value only in the earliest
stage of the disease, and in this way only was it that
Koch hoped to do good by the use of his “lymph”
against tuberculosis. If the harmful and helpful

52 ESSAYS ON BACTERIOLOGY.

agents are different, then, could we but isolate the
latter, we might use it at any stage of the disease, and
only with benefit.

Then, too, the question arises whether the agents
producing self-limitation and immunity are the same,
and the possibility, if different, of separating and ob-
taining them for practical use. We must also ask
ourselves whether it is always or usually possible to
obtain the desired substances from artificial cultures
of the germs. May there not be processes attending
the growth of the germs in the living body which are
not possible in the artificial experiments? For, as
Frenkel aptly reminds us, the living tissue is no plate
of gelatine and no test-tube. How far this may prove
an obstacle to progress is as yet uncertain; but it is
certain that it does not necessarily and always forbid
success by the artificial method.

Here we see two schools of experimenters arising.
The one excludes the living germ, seeking and using
only the sterile germ products. This they do under
the belief that, could the problems indicated be solved,
and the processes be worked out to exactness by chem-
istry, the method would be more accurate and less
dangerous. For, thus far, experiments made with
even weakened living germs have proven to be accom-
panied by more or less risk.

The other school, acting upon the conviction that
artificial culture cannot be relied upon to produce the
same results as germ-growth in the living tissues, uses

+

ESSAYS ON BACTERIOLOGY. 53

the living germs, but weakened, claiming thus to
more closely imitate nature. This weakening or at-
tenuation of the virus is brought about in various
ways: by altering the culture soil, by heat, gases; vary-
ing atmospheric pressure, drying, and by passing the
germs through the bodies of animals. Pasteur started
the line of work which has made him famous upon
the supposition that vaccinia was simply smallpox
modified by passing through the body of the cow.
Whether this is true or not, his theory of the use of
attenuated virus proved correct, and led to the aston-
ishing results in the diseases already mentioned.
Which line of work will best sustain its claims in the
end remains for the future to decide. Certainly thus
far the living virus seems to have the more to its
credit.

Let us now look for a moment at several other in-
teresting facts, to which I shall refer but briefly be-
fore attempting to sum up the matter of our discus-
sion.

First, as already indicated, the blood, or body
juices, of animals, naturally immune, may afford |
more or less protection to susceptible animals against
a disease to which the one isimmune. This fact may
open the way to some valuable results.

Second, it may ultimately be found that the appar-
ent absence, or slight tendency to self-limitation and
immunity in certain diseases, is only apparent; that
these tendencies are present, but are overcome by an-

54 ESSAYS ON BACTERIOLOGY.

tagonizing agents. If, then, it shall be found that
the harmful and the helpful agents are different, and
the latter can be separately obtained, we may be able
to use them successfully even in diseases, such as tu-
berculosis, which, under ordinary conditions, show |
little or no tendency to self-limitation or immunity.
Such an effort has been made with the tuberculin of
Koch.

Third, It has long been observed that the presence
of certain diseases in the body seemed to exclude, or
oppose, the entrance of others, and it is now known
that there is an antagonism between certain bacteria.
Such antagonism may be shown, not only on the cul-
ture-plate, but in the body. Thus, rabbits inoculated
with the intensely virulent anthrax may be saved from
death. by introducing, shortly before or after such
inoculation, the micrococeus prodigiosus. Here is an
example of cure of a malignant disease: If cowpox
is not simply modified smallpox, vaccination may be
said to be an example of immunity afforded through
such antagonism. In both examples the beneficial
agent is practically harmless. It is by no means im-
possible that here may be found a clue to success with
our efforts.

In conclusion, Jet us sum up the whole matter and
see where we stand to-day, and what grounds we have
for entertaining a hopeful prospect. It will be no-
ticed, as we review the questions under discussion and
study the various plans suggested by bacteriological

ESSAYS ON BACTERIOLOGY, 55

investigations for the attack upon the infectious dis-
eases, that they fall into two general groups: First,
those based upon the facts observed in the ordinary
course of the infectious diseases; second, those based
upon facts coming from other directions. What ex-
pectation or hopes open now before us in this great
field?

If, as to the questions of self-limitation and im-
munity, we study the infectious diseases, we shall find
that they fall into three quite distinct classes.

First, there is a class of these diseases in which both
self-limitation ‘and immunity are practically absolute.
Such are measles, scarlatina, smallpox, typhoid fever.
This being true, we might hope to command the situ-
ation, so far as immmnity is concerned, if we could
secure an attenuated virus or the chemical products
of their germs. It would hardly seem that we could
expect to accomplish much in the way of cure, even
by an attenuated virus, since by this process we
should subject the already crippled body to something
of the harmful as well as helpful agents. But pro-
vided these agents are different, and we could obtain
the latter, we might then have settled even the matter
of cure.

The second class includes diseases in which self-
limitation is absolute, but subsequent immunity is
slight, or wanting. Here we find such affections as
diphtheria, erysipelas and pneumonia. With these
the problem of cure would be the same as before. But

56 ESSAYS ON BACTERIOLOGY.

what of immunity? If the natural process does not
afford it, experiment along this line would not seem
promising.

Of the third class, in which both self-limitation and
immunity are slight or wanting, tuberculosis is a type.
And here the prospect in either direction seems dark.
With the facts of the natural history before us, what
can be expected from an imitation of that process?
And yet the suggestion hitherto made in regard to
tuberculosis may be true. It may be that there is an
agent of self-limitation which only waits to be found
and isolated, which, freed from the antagonism of
others, may furnish an unexpected escape from de-
feat. Or here, and elsewhere, where the outlook
seems very doubtful, the facts coming in other direc-
tions may give light, indicating that the way to suc-
cess is to be sought, not in initiating the natural course
of events, but in utilizing agents obtained from ani-
mals possessing a natural immunity; by pushing fur-
ther the investigations upon the antagonism between
different bacteria, or by some means yet to be discov-
ered. If it is possible to cure malaria by quinine; to
drown the yeast germ in its own secretion; to guard
against diphtheria or tetanus by the blood of protected
animals; to jugulate malignant anthrax by the harm-
less prodigiosus, why should it be thought impossible
to carry the work farther, to conquer even the great
destroyer, tuberculosis?

The contest is really but just begun, and we are, as

ESSAYS ON BACTERIOLOGY. 57

yet, too often at the mercy of the almost invisible foes
which prey upon and destroy the majority of our race.
But we are steadily advancing in knowledge, which is
power, and one day we shall conquer. It may be by
this means, it may be by that, but we shall conquer.
One day, we believe, we shall issue to the pestiferous
brood the authoritative command: Out upon you;
hence, begone!

V.
THE CONTEST AGAINST INFECTION.

it

[' has become evident that bacteriology is now pro-

gressing chiefly in the direction of discovering the
channels through which the self-limitation of and im-
munity from infectious diseases is brought about. As
stated heretofore, enough has been learned to estab-
lish the principle that the effects of bacteria are pro-
duced by chemical substances contained in their bodies
or resulting from the growth of these bacteria. Suffi-
cient also has been learned to show that self-limitation
and immunity are in some way the outcome of such
substances. The question, therefore, presents itself:
What is immunity, and through what channels and
by what agents is it brought about?

— At the outset we must recognize two forms of im-
munity: first, natural immunity, by which is meant a
natural insusceptibility of certain animals to certain
diseases; second, acquired immunity.

Acquired immunity may be brought about in three
ways: First, by an attack of the disease; second, by
inoculation with an allied disease or with the disease
modified by passing the virus through another animal;

58

ESSAYS ON RACTERIOLOGY. 59

third, by the virus modified by culture outside of the
body. How are these results brought about?
Among the various theories are two which have as-
sumed prominence. First, the phagocytosis theory
of Metschnikoff, which supposes that certain cells of
the body are active agents in the warfare against in-
fection. In following out this theory Metschnikoff
has displayed a remarkable degree of ingenuity, pa-
tience and skill, and has brought out some exceedingly
interesting and important facts. The other theory is
that the protective agents are to be found in the blood
and body juices. As the result of the work of the
last year or two it must be said that opinion tends
strongly in the direction of the second view. Von
Fodor finds, as the result of a series of experiments
and researches, that arterial blood has more anti-bac-
terial influence than venous; that fresh blood has more
influence than old; that the maximum anti-bacterial
power of the blood is at the temperature of 100° to
104° F.; that the individual susceptibility of an ani-'
mal to an infectious disease seems to be in direct rela-
tionship to the germicidal power of its blood; that
various chemical and other agents diminish while
others increase this power, the most marked increase
being brought about by carbonate of sodium and po-
tassium: He concluded that any agent which in-
creases the alkalinity of the blood increased the resist-
ing power of the organism against bacteria. A serics
of experiments made on this basis seems to prove the
correctness of the theory. .

60 ESSAYS ON BACTERIOLOGY.

Naturally, as the result of these discoveries, the at-
tempt has been made to find a bactericidal agent in
the blood. Hankin has been a leader in this special
work. He believes that he has established, for cer-
tain animals at least, that the blood contains a sub-
stance of a proteid nature which belongs to the globu-
lins and has certain bactericidal properties. Follow-
ing this supposition, he was able to neutralize inocula-
tions of anthrax by injection of a solution of this glob-
ulin. The tendency of investigation is unmistakably
in at least the general direction of Hankin’s view.

These albuminoid substances have been called de-
fensive proteids, and investigation seems to indicate
that they may act in one of three ways: first, by kill-
ing the bacteria, that is, microbicidal; second, by at-
tenuating or weakening the bacteria; third, by neu-
tralizing or destroying the toxines. In justice to the ~
work of Metschnikoff it must be said that this blood
serum theory does not necessarily disprove his phago-
cytosis theory, for it is still quite possible that self-
limitation or immunity, or both, may result from
these defensive proteids acting upon or through the
cells.

Behring and Kitasato found that the serum of rab-
bits vaccinated against tetanus had the property of de-
stroying the toxin of tetanus in guinea pigs, so that
guinea pigs might be cured of tetanus by injection of
rabbit serum taken from vaccinated rabbits. The
same authors proved a similar fact in regard to diph-

ESSAYS ON BACTERIOLOGY. 61

theria. Already it is reported that clinical use has
been made of this discovery in actually curing some
six or seven cases of tetanus in men. Tlie first ex-
periments in this direction were made by transfusion
of the whole blood. Subsequently it was found that
the protecting properties resided not in the corpuscles
but in the serum.

It is to be noted here that these defensive proteids
are not general in their action; that is, serum, or a de-
fensive proteid derived from it, which will protect
against one disease will not necessarily protect against
others. We cannot, therefore, at present entertain
the idea of discovering a universal bactericidal agent
of blood serum, sufficient at least for use as a general
protective. Hankin suggests a classification of these
defensive proteids into two groups: first, those exist-
ing naturally in animals, and these he calls sozins;
second, those existing in animals artificially made im-
mune, which he calls phyloxins. For sub-classes he
suggests the prefixes mico- and toxo- to indicate so-
zins or phyloxins which destroy bacteria or which de-
stroy toxins. Emmerich, in summing up his re-
searches, claims to have established two important
principles: first, that the cause of artificial immunity
is an anti-bacterial substance which is not injurious to
the body; and second, that the protective fluid for
one class of animals may be applied against that par-
ticular disease in other classes of animals. For in-
stance, that the fluid from protected rabbits could be

62 ESSAYS ON BACTERIOLOGY.

successfully used to cure infected swine. He claims,
says Ernst, that he has by these experiments entered
upon the first stage of a certain and rational treatment.
of infectious disease, and urges it to be the duty of all
to strive for the attainment of an ideal that must com-
plete the discovery and manufacture of the true anti-
bacterial material. The time is perhaps not far dis-
tant when such a material will be in the hands of all
who are called on to treat infectious diseases. Other
diseases besides swine fever are already under investi-
gation. It will be noted by the study of this whole
matter that the tendency now is to use the natural
laboratory, that is, the living body, rather than arti-
ficial cultures to secure these protective agents.

In summing up this matter, in order to indicate the
present status of the contest against infection, I make
the following brief statement as an indication of the
best present opinion:

First. The infectious diseases are due to living
agents.

Second. Bacteria injure the body and cause sick-
ness through the production of poisonous substances
called, loosely, ptomaines or toxins.

Third. Self-limitation and immunity are in some
way, directly or indirectly, brought about by the ac-
tion of such chemical substances, the protective
agents, however, not being necessarily the same as
those which cause the sickness.

Fourth. These protective agents may be found in
the blood serum and body juices.

ESSAYS ON BACTERIOLOGY. 63

Fifth. Their protective action may be a direct
one, or it may be exerted through certain cells called
phagocytes, the former seeming at present the most
probable.

Sixth. Natural or acquired immunity may be
transferred from one animal to another by the trans-
fer of blood serum.

Seventh. Following out the indications from these
facts, sufficient practical su¢cess has been achieved to
make the most conservative almost an enthusiast, and
to furnish ground for a rational hope and expectation
of further success.

The following prediction is made by Ernst: “In
spite of the great number of unknown points that still
surround this new theory of immunity by defensive
proteids, it can already be predicted that it will come
out victorious in the struggle in which it is engaged,
with the numberless hypotheses and the old prejudices
that surround and encumber this branch of general
pathology. It will be victorious, for it has already
given certain proofs of its importance by vaccinating
and curing animals by means of these defensive pro-
teids.”

A brief review now of work done with some of the
specific bacteria:

1. Cholera.—Nothing has really been done to
overthrow Koch’s previous work. Klein, of London,
has expressed skepticism in regard to the comma bacil-
lus of cholera as a specific organism, quoting the in-

64 ESSAYS ON BACTERIOLOGY.

vestigations of Cunningham, in India, who claims to
have recognized several different species of comma
bacilli in cholera. The value and meaning of these
claims remain as yet doubtful. It is interesting to
note the experiment of Pettenkofer, who voluntarily
swallowed pure cultures of comma bacilli brought
fresh from Hamburg. He did this to show his con-
tempt for these organisms as the active cause of chol-
era. The result of his self-inoculation was a moder-
ate sickness, which he asserted not to be cholera, but
which less prejudiced authorities believe to have been
simply a mild cholera, the discharges from the bowels
containing almost pure cultures of the comma bacilli.
Another experimenter, actuated by the same motive,
produced in himself similar results, except that the
sickness was more severe. It is of practical interest
also that, upon the approach of cholera to New York -
recently, the presence of the comma bacilli in the de-
jections was successfully used as a test of the exist-
ence of the disease in suspected cases.

2. Cancer.—Many observations have been made
of peculiar bodies in cancerous tissue. These have
mostly been placed in the class coccidia. Their in-
vestigation is so difficult, artificial cultivation so elu-
sive, and their relation to the tissue cells so peculiar,
that it is difficult to decide their biological position.
The question is, therefore, still unsettled. Domergue
is inclined to believe these coccidia to be simply cell
transformations. There are, however, those who take
a different view, who believe them to be true parasites.

ESSAYS ON BACTERIOLOGY. 65

3. Dysentery—Evidence upon the pathogenic
properties of the amceba coli has been accumulating.
Kartulis claims to have secured pure cultures of the
amoeba in decoctions of fresh straw. He claims also
to have made successful inoculations in cats. Owing
to the work of many foreign investigators and of
Councilman, Welsh, Osler and others in America, the
diagnostic value of the amceba coli seems to have been
well established, as also its causative relation to other
than dysenteric lesions, especially to hepatic abscesses.

4. Diphtheria—No important change has oc-
curred in the bacteriology of this disease. Previous
opinions have simply been strengthened. Recent in-
vestigations seem to show that the diphtheria bacilli
are secondarily diffused through the body more fre-
quently than has been heretofore supposed. The
most important work on diphtheria has been that al-
ready mentioned, namely, the successful protective
and curative experiments of Behring and Kitasato.

5. Erysipelas.—The uncertainty as to the identity
of the streptococcus of erysipelas and the streptococcus
pyrogenes remains. Frenkel, among others, has
done work which seems to give additional proof of the
identity of these organisms.

6. Gonorrhea.—I have only to repeat and em-
phasize a statement made in a former report, that
while the microscopic discovery of the gonococcus
may be looked upon as very strong evidence for patho-
logical and clinical purposes, its medico-legal value is-

5

66 ESSAYS ON BACTERIOLOGY.

doubtful. We are not in position as yet to make ab-
solute statements in court as to the diagnostic impor-
tance of the gonococcus, at least as found by the mi-
croscope alone.

7. Smallpox and Vaccination.—Renewed interest
has been taken and renewed activity shown. in investi-
gating the question of the identity of variola and vac-
cinia. Unmistakably the tendency of experiments is
to confirm the view that vaccinia is nothing but vari-
ola modified by passing through the cow. This
might and would seem strange were it not for the fact
that the last ten years has shown that the virus of
many other diseases may be much modified by pas-
sage through the body of certain animals. It is quite
possible that we shall soon have established the fact
that variola is inoculable upon the cow, if the inocula-
tion is properly made—that such inoculation becomes
changed after efficient repetition into vaccinia, and
that inoculation in this way affords an always con-
trollable means of obtaining animal vaccine.

8. Bacillus Pyocyaneus.—The microbe of green
pus has risen into prominence and importance, chiefly
because of its remarkable influence in arresting the
development of anthrax when inoculated at about the
same time as that virulent germ.

9. Malaria.—The diagnostic value of the malarial
plasmodia remains high; indeed, the best opinion
tends to make it absolute. The work of Osler, Welsh,
and Councilman in this country, and of Laveran,

ESSAYS ON BACTERIOLOGY. 67

Golgi, Rosenbach and others among foreigners, has
continued. Rosenbach has shown the interesting
fact that the malarial parasite can be kept alive for at
least forty-eight hours in the digestive canal of the
leech.

10. Purulent Pleurisy—The subject of purulent
pleurisy has continued to attract investigation. The
result is a tendency to include all, or nearly all, puru-
lent plurisies in three groups: First, those due to the
Sternberg-Frenkel pneumococcus; second, those ex-
cited by the pyogenic staphylococci; third, those due
to tubercle bacilli. Microscopic examination or culti-
vation or inoculation experiments will show the char-
acter of the case; and of this knowledge real, practical
clinical use may be made.

11. Tetanus.—The previously expressed views as
to the specific nature of the tetanus bacilli have been
confirmed. Every one now believes that the specific
bacterial origin of this disease has been established.
The most interesting outcome of recent work has been
the prevention and cure of tetanus by the use of blood
serum or defensive proteids. Mention has already
been made of the apparently successful practice of
such cure upon men.

12. Tuberculosis—Time only increases our ad-
miration of the marvelous piece of scientific work re-
vealed in Koch’s announcement of his discovery of the
specific cause of tuberculosis. Time also only adds
emphasis to the practical diagnostic value of this dis-

68 ESSAYS ON BACTERIOLOGY.

covery and the importance of its daily use. Some
improvements have been made in the methods of ex-
amining sputum which enable us to reach certainty in
otherwise doubtful cases. These are, first, liquefac-
tion of the sputum by the addition of a small quantity
of dilute sodium hydrate. Such liquefied sputum is
allowed to settle in a conical vessel, and the sediment
examined for bacilli by the ordinary means. Second,
the addition of liquid carbolic acid precipitates the
bacilli-containing masses in the sputum, which may
be examined with increased prospect of finding the
few bacilli present. Third, the centrifugal machine
has been applied for a similar purpose, just as it is ap-
plied to secure the rapid deposits of urinary casts.

I would, in this connection, emphasize the value
and simplicity of inoculations upon rabbits or guinea
pigs for diagnostic purposes in otherwise obscure
cases.

So far as we can now tell, the tuberculin experi-
ment of Koch to arrest tuberculosis has been a failure.
We now know more of the reason for expecting such
failure than we did when the treatment was promul-
gated. However, no one conversant with the prog-
ress of bacteriology supposes for a moment that this
failure will, or should, dishearten us or arrest further
experiment in this and other diseases. Through the
work of ITunter, Cheyne, Klebs and others it has been
shown that even Koch himself was ignorant of the
substance with which he was dealing, the two former

ESSAYS ON BACTERIOLOGY. 69

authors having thought to modify and improve Koch’s
tuberculin by excluding some of the harmful constit-
uents. Klebs has claimed to accomplish the same re-
sult, and considerable interest has been taken in his
modified tuberculin, the so-called tuberculo-cidin. In
spite of these claims, it is evident that the results
gained by following this particular line of experi-
ments has not been great. It evidently yet remains
to find an agent which approaches a specific for tuber-
culosis. Nevertheless, bearing in mind the remark-
able developments of the last few years, the great
progress made in clearing up the mystery of proteids,
and remembering the astonishing antagonism which
may exist between different bacteria, even between
harmless and virulent ones, there is certainly room for
hope. I believe that the day will come, it may come
soon, it may be long delayed, but the day will come
when tuberculosis will be as thoroughly at our mercy
as is smallpox to-day. It will have sunk to the insig-
nificance of a beaten and imprisoned enemy. I hope
and expect to see it before my hair has grown gray.

VI.

RETROSPECT AND PROSPECT OF
PROGRESS.

OUR years have passed since the paper upon

“Some Problems of Bacteriology’ was written.
Times change and we change with them, and such
change is no disgrace provided it consists in progress
toward truth. That during these four years modifi-
cations of views have come about, supposed facts have
been shown to be deceptive, new truths have come to
light and broader conceptions of matters bacteriolog-
ical have developed, goes without saying.

It may, therefore, not be out of place to review
some of the statements contained in former essays,
that we may see how far modifications are necessary
to adapt these statements to present knowledge, and
how much nearer we have come to established truth.
As we proceed in this review it will become evident
that in some directions there has been a simplification
which is to be expected as the field clears and we come
nearer to the great and fundamental truths.

In other directions progress has served but to show
into what an immense field we have entered. In
some directions final truth has been reached or is near
at hand; in others it is evidently as yet afar off. But

70

ESSAYS ON BACTERIOLOGY. 71

the prospect is inviting; progress brings a constant suc-
cession of fulfilled expectations, equally unexpected
disappointments, startling surprises, suddenly opening
avenues for the advance, and that the final results will
be great and good no one can doubt.

We are stil! confronted by the difficulty in making
satisfactory inoculation tests in several of the impor-
tant diseases, the specific bacteria of which are all but
demonstrated. This is still true of typhoid fever and
Asiatic cholera. So far as we know, animals are not
subject to these diseases, at least not in a definitely
recognizable form. While, therefore, there can be
little doubt that the Koch-Eberth bacillus and the
Koch spirillum are the genuine exciters of these dis-
eases, the final and absolute step in the demonstration
remains to be taken. Several bold experimenters
have swallowed fresh cultures of cholera spirilla, in
several instances inducing moderate attacks of a dis-
order similar to cholera, with swarms of the organ-
isms in the stools. Among these daring men was the
veteran Pettenkofer, whose object was to show that
other factors than the germs were at least active in
the production of the disease. In one instance, under
the observation of the well-known Metschnikoff,a man
in Paris induced a typical attack of cholera by swal-
lowing a pure culture, and that in the absence of chol-
era in Paris at the time. This is held by some to be
conclusive evidence; but we can hardly be satisfied
without a more thorough test.

72 ESSAYS ON BACTERIOLOGY.

Even though this obstacle to experiment remain,
there are other, though indirect, means of demon-
strating the specific relation of a given bacterium to a
disease. For instance, if it be shown that a certain
germ may be used to furnish a successful vaccine, a
defensive proteid, or immunizing blood-serum, against
the disease from which it was obtained, the fact goes
far toward proving that germ to be the specific exciter
of that disease. Thus the road, blocked in one direc-
tion, opens up in another.

As to the question whether each of the infectious
diseases has a single specific causative agent, the an-
swer may now be more satisfactory. There are some
maladies of which it seems to have been abundantly
shown that this is true; for instance, tuberculosis and
glanders. There are others, however, which have or-
dinarily been looked upon as specific diseases, of which
we now take a different view. Among these are the
septic and inflammatory affections “which do not pre-
sent such sharp and definite differential characters as
do those more specific infectious diseases which arc
caused by only a single species of micro-organism.
Some of these present clinical and pathological differ-
ences in accordance with their etiological differences,
whereas others do not. To this class belong acute ul-
cerative endocarditis, meningitis, broncho-pneumonia,
erysipelas, pyemia, septicemia, osteomyelitis, and pu-
erperal fever. Most of these names are simply col-
lective terms for different diseases which have already

ESSAYS ON BACTERIOLOGY. 73

received, or are likely still: further to receive, more
exact definition as the result of bacteriological studies”
(Welch).

Upon antisepsis and disinfection there is little new
to be said. They have been worked out, for all prac-
tical purposes, to fair satisfaction. ‘The methods of
testing disinfectants remain as, before; their practical
application is being constantly improved, but in de-
tails only. Every one knows that asepsis in surgery
has taken precedence over antisepsis as formerly ap-
plied, and every one understands the reasons for the
change. The reason is simply the old one that pre-
vention is better than cure. But, be it remembered,.
there is still and there will doubtless remain an im-
portant field for antisepsis, and for just the same rea-
sons that there remains and will remain the necessity
for curative as well as preventive measures in general
medical practice. The necessity for antisepsis and
for curative measures will remain just as long as in-
fecting and other pathogenic agents precede the ad-
vent of the surgeon or physician.

Investigators are still battling with the problem of
the hereditary transmission of the infectious diseases,
and the matter is by no means yet settled.

It is settled that offspring may come into the world
with the germs of disease in their bodies. But just
how frequent this is and how far it must be taken into
account in everyday practice and sanitary science, is,
with some diseases, still uncertain. Here, as always,

74 ESSAYS ON BACTERIOLOGY.

interest centers around tuberculosis. It is generally
conceded that family history plays an important role
in this disease; but whether this is to be laid chiefly to
the charge of some general or special predisposition,
of infection growing out of closer association or of
house contamination, or of actual hereditary trans-
mission of the disease germs, remains open to debate.
Baumgarten has steadfastly and earnestly advocated
the latter view, which is rendered more plausible by
the accumulating facts as to the possibility of tubercle
germs remaining long latent in the living body. Yet
there are many things to be explained before we can
accept Baumgarten’s view. In the meantime noth-
ing has been brought to light to in any way shake the
great truth that tuberculosis is to be included among
the specific infectious diseases, and that multitudes
are falling victims to this infection in the ordinary
way. The chronic character of the malady, the many
secondary factors influencing its inception and prog-
ress, and above all its long period of incubation, these
things alone prevent the general recognition of its in-
fectious character as clearly as that of measles, scarla-
tina or smallpox. Surely the time will not be long
before failure of such recognition and consequent ac-
tion will be properly held as evidence of criminal
neglect.

In a former paper I endeavored to summarize
briefly the status of our knowledge as to the relation-
ship ‘between particular disease and particular bac-

ESSAYS ON BACTERIOLOGY. 75

teria. Something additional may be acceptable in
this line to bring the subject up to date.

First, Tuberculosis—One of the most important
matters in the study of this disease has been the dem-
onstration that tubercle bacilli may long remain latent
or dormant in the body, to be called into. activity by
various exciting agencies. Thus the bronchial glands
have been repeatedly shown to contain living-tubercle

bacilli while the lungs and other organs were appar-
ently free both from the germs and the disease. This
fact doubtless explains many cases of acute tubercu-
losis following such diseases as measles, whooping
cough and typhoid fever, and slight wounds to bones
and joints. Furthermore, proof positive has been ac-
cumulating that actual congenital transmission of tu-
berculosis is more frequent than was a few years ago
supposed. To be sure, these demonstrations have
been comparatively few, but they seem to strengthen
the view of Baumgarten, to which reference has al-
ready been made.

A review of tuberculosis would be incomplete with-
out reference to the efforts which are being awakened
the world over to limit the spread of the disease by
limiting the distribution of the poison. Already a
number of foreign and American sanitary boards have
instituted formal measures in this direction. The
New York City Board of Health has here again dem-
onstrated its progressive efficiency. The question of
compulsory notification of tuberculosis has given rise

76 ESSAYS ON BACTERIOLOGY.

to sharp debate, for well-known reasons; but upon the
necessity of some measures to restrict the reckless
spread of this dread agent of destruction, there can be
no difference of opinion. The fact that the material
coming from tuberculous lesions contains a living
_ poison, capable, whether upor the clothing, the floors,
the walls, or in the dust of the air, of exciting the dis-
ease; this fact, IT say, is sufficient warrant for some
measures looking to the protection of the public
against the danger. But whatever is done must be
done carefully, wisely, and under the direction of
those who understand the facts and the conditions un-
der which the action must be carried out, and who can
take broad, well-balanced views of the situation.
Tetanus.—There seems to be no longer any ques-
tion that the tetanus bacillus of Nicolaier and Kita-
sato is the specific cause of that malady. This has
been confirmed not only by the cultivation and inocu-
lation experiments, but in the production of artificial
immunity through the agency of the same germ.
Reference will be made to this matter later.
_ Diphtheria—There is now an apparently unani-
mous opinion that the Klebs-Leeffler bacillus is the
specific cause of diphtheria; that the exudative sore
throats accompanying scarlatina, measles, and other
acute diseases, while sometimes diphtheria, are usu-
ally of different origin, though not rarely of no less
gravity. It seems further agreed that the examina-
tion for the Klebs-Lceffler bacillus may be made of

ESSAYS ON BACTERIOLOGY. 77

great practical value in diagnosis. Further, it has
been shown that, while the diphtheria bacilli are not
usually disseminated through the body, they may be
carried about and set up secondary infection, giving
rise to acute ulcerative endocarditis and other lesions.
Finally, we are apparently nearing a solution of the .
vexed question of the relationship between diphtheria
and membranous croup. The writer has reported some
investigations in this line. Of late several boards of
health, which are conducted upon scientific rather
than political lines, have been giving close study to
the problem, and with somewhat startling results.
The pathologists of the New York board have exam-
ined several hundred reported cases of membranous
croup, finding the diphtheria germs present in about
80 per cent. Corresponding results have been
reached in other’ cities. The New York board has
therefore recommended that membranous croup, so
called, should be included among the diseases to be
reported by the physician for the purpose of institut-
ing protective measures. Whether all cases of mem-
branous croup are simply laryngeal diphtheria re-
mains to be settled by further and more exhaustive
studies. In the meantime it may fairly be asked
whether the report of about a hundred deaths from
membranous croup in this city during the last three
years does not come near to being an example of gross
professional carelessness.

Something more might be said in regard to some of

78 ESSAYS ON BACTERIOLOGY.

the specific bacteria, but perhaps little of importance
in addition to what has already been said. I turn,
therefore, to a brief survey of that rising field of work
in which all are deeply interested, namely, the inves-
tigations upon immunity from and protection against
the infectious diseases.

An immense amount of work is being done in this
direction; hap-hazard experiments are becoming
fewer, and the whole matter is steadily being reduced
to a more scientific basis. We now recognize several
ways of securing a more or less lasting immunity
against many of these diseases, and there is opening up
a new field, already promising, in the way of cure for
those laboring under an attack. It would require a
long time to even briefly review this great mass of
work, and present its results. I can, therefore, only
note some interesting and leading points. As I have
said, there are several ways by which a more or less
lasting immunity may be secured.

First. By inoculation of such amounts of living
and virulent cultures of the microbe causing the dis-
ease as shall fall short of a fatal result. An example
of this was the practice of inoculation against small-
pox, which preceded the far safer and about as equally
successful vaccination worked out by Jenner.

Second. Inoculation of the specific microbe partly
or wholly attenuated in virulence, this attenuation be-
ing secured by: various means, such as culture under
peculiar conditions, or passing the germs through the

ESSAYS ON BACTERIOLOGY. 79

bodies of certain animals. Of this method the vac-
cination of Jenner is probably an example.

Third. The injection of products of the specific
bacteria, these products being obtained from cultures
or from the bodies of infected animals. They may be
used when still toxic, or, more frequently, after dimin-
ution or removal of their toxicity. :

The principal means of reducing toxicity and in-
creasing vaccinating values are heat and mixture with
certain animal juices, particularly thymus extract, or
with tri-chloride of iodine and some other agents in-
jurious to bacterial poisons.

The so-called chemical vaccines belong to this class.
They have a very wide field of application. In some
instances partial immunity -has followed the introduc-
tion of this class of substances into the stomach.

Fourth. Injection of blood-serum or other fluids
from animals artificially rendered immune from the
disease. As the blood-serum from immunized ani-
mals may possess not only prophylactic but curative
properties, it has been called curative or healing
serum.

Usually various methods can be successfully em-
ployed in producing artificial immunity from a given
disease.

It is a general rule that a given microbe and its
products are capable of conferring immunity only
from the disease which is caused by that microbe.

The conferred immunity may be increased in de-

80 ESSAYS ON BACTERIOLOGY.

gree and durability by the gradual use of vaccines of
increasing strength, followed by inoculations of the
virulent microbes or their products, until an astonish-
ingly high degree of insusceptibility may be reached;
such a degree, indeed, that immense quantities of the
most virulent microbes may be introduced without
harm.

Following some of these methods of immunization,
an animal may sometimes be protected against the
growth of the bacteria in the body, while it still re- .
mains susceptible to the toxic products of that bac-
terium; and vice versa.

Some of the so-called antitoxins obtained from the
blood serum may be obtained in far greater concentra-
tion than that in which they exist in the original
fluids. It is to be hoped that this work may be car-
ried still further.

It has been found that, once an animal has been
successfully immunized, the successive injection of in-
creasing quantities of the toxic substances may bring
about an enormous increase in the antitoxic or im-
munizing power of the body fluid of that animal. In
tetanus, for instance, the point may thus be reached
where 1 c. c. of serum is sufficient to immunize
500,000 mice weighing 20 gm. each, or 200 sheep of
ordinary weight.

The blood-serum therapy for the cure of disease al-
ready under way has been most thoroughly worked
out in diphtheria and tetanus. The curative value of

ESSAYS ON BACTERIOLOGY. 81

the serum is in direct proportion to the quantity intro-
duced and to the degree of immunity previously con-
ferred upon the animal from which the serum was
obtained.

The stage and intensity of the attack have much
influence upon the results obtained by this blood-
serum therapy. The longer the attack has lasted and
the more intense it is, the greater the quantity of
serum necessary to arrest its progress. This resist-
ance to the serum rises very rapidly, so rapidly, in-
deed, as to soon reach such a point as to require an
amount of serum impossible to introduce into the ani-
mal. Hence the desirability of progress in the direc-
tion of securing the immunizing or curative agent
from the serum in some more concentrated form. In
regard to the difficulty just referred to, it is less in
diphtheria than in tetanus.

There are still many difficulties in the application
of: this serum therapy to the larger animals and to
man. Already considerable success seems to have
been reached in its application to human tetanus and
diphtheria, but it is yet too early to predict what the
outcome may be. The conditions in the laboratory
are quite different from those at the bedside, and we
must be careful how we carry over inferences and ex-
periments from one to the other. At present we can
but maintain an attitude of hopeful expectation,
strong in the conviction that sooner or later every
gain in knowledge will result in practical good.

6

VII.

ANTITOXIC SERUM THERAPY.

N view of recent events, the consideration of serum
therapy in general and of the antitoxic serum
treatment of diphtheria in particular is of the greatest
interest. Reference has been made to the progress of
investigations in this direction, and to the fact that
already this new principle of treatment, prophylactic
and curative, had been brought to the point of a prac-
tical test. As every one knows, it has engaged the
intense interest and attention of the world. Having
thus established for itself a place in the history of
medical progress, it will be well to briefly survey its
origin and development.

I have already discussed the various methods, the
outgrowths of modern bacteriology, which have, with
more or less success, been tried in the attempt to imi-
tate or improve upon nature in securing an immunity
from or cure of infectious diseases. These experi-
ments have been based upon the discovery that, the
infectious diseases being due to germs, their phenom-
ena, including self-cure, and subsequent immunity,
were in some way the results of the presence of the

82

ale

ESSAYS ON BACTERIOLOGY. 83
«

chemical products of germs acting upon the living or-
ganism. In the endeavor to imitate or improve upon
nature in this direction the tendency has been unmis-
takably to make use of what may be called the natural
laboratory, that is, the animal body.

Several important discoveries have combined to
give us the new serum therapy.

1. It was found that the blood and other body
fluids had a certain amount of bactericidal power.
This may be said to have been the starting point of the
long line of investigations which have centered in the
blood.

2. It was found that, imitating nature, animals
could be rendered immune to certain diseases by in-
troducing into their bodies the germs or the toxic
products of the specific germs which caused the dis-
eases.

3. Carrying these experiments further, it was
found that by a process of progressive inoculations
from weaker to more virulent germs, or of injections
of smaller to larger quantities of toxins, a progressive
degree of resisting power to those germs or toxins
could be developed. The degree to which this rise of
resisting power can be carried is indeed astonishing.

4. When the agency of this artificially induced
resisting power came to be investigated, it was found
to apparently have its seat in the blood. |

5. And now the surprising and epoch-making dis-
covery was added that this resisting power, thus arti-

84 ESSAYS ON BACTERIOLOGY.

ficially developed in one animal, could, by the trans-
fer of the blood, be transferred to another animal
which was previously susceptible. Bacteriology hav-
ing reached the stage of advancement that it had, it
did not take long to settle the fact that this series of
investigations had culminated in a most important
practical discovery. It was fully demonstrated that
a method, comparatively simple and apparently free
from harm, had been found, by which animals could
be protected against certain diseases, notably tetanus
and diphtheria, and could with equal certainty be
cured when those diseases had already entered the
body.

The experiments upon human beings were then be-
gun, at first upon a small scale, then more extensively,
and with the results now known to all. This work
has been done by scientists in a scientific spirit, and, to
the credit of scientific medicine be it said, there is no
secrecy and no degrading proprietorship in it.

Speaking now more particularly of diphtheria, the
antitoxic serum is prepared as follows: Cultures of
the most virulent diphtheria germs are allowed to

grow in a fluid medium for several weeks. The fluid
is now found to contain the diphtheria toxin, an in-

tensely powerful poison. Small, non-fatal quantities
of this toxin are injected into an animal, usually a
horse. At intervals, of some days, progressively in-
creasing quantities are injected, the result being the
development of a correspondingly progressive resist-

ESSAYS ON BACTERIOLOGY. 85

ing power in the animal. Finally, a condition is
reached in which the animal is able to resist enormous
quantities of the poison. The blood is now drawn,
allowed to clot, the serum removed, and, after filtra-
tion and the addition of a small per cent. of antiseptic,
is ready for use. This serum it is which seems to con-

tain the antitoxic agent, and whose injection into a
susceptible animal confers wpon that animal, for a

variable and limited time, the resisting power of the
animal from which it was taken. This serum it is,
also, which is injected into human beings exposed to
or already sick with diphtheria. .

I shall not now array the statistics which have been
presented for and against this new treatment, which
we owe chiefly to the labors of Behring and Kitasato
in Germany, and Roux in France. Perhaps the
most significant .and most influential are those
published by Virchow, summarizing the experi-
ence in the Emperor and Empress Frederic Hos-
pital in Berlin. During a given period between five
and six hundred cases of proven diphtheria were in
the hospital. Of these over three hundred were
treated with the serum, with a mortality of about 13
per cent. Over two hundred, treated without the
serum, gave a mortality of about 47 per cent. Equally
significant was the fact that when, at times, the serum
treatment was suspended the mortality at once rose, to
fall again promptly with the resumption of the anti-
toxin therapy. The known conservatism of Virchow

86. ESSAYS ON BACTERIOLOGY.

in such matters, together with his equally known
shrewdness as an observer, have therefore given much
weight to his favorable judgment of the treatment.
Theorizing, he says, must give way to the brute force
of these facts.

All of the experiments upon animals show that the
prophylactic powers of antitoxic serums is their great-
est; that here their power is practically absolute; that
their curative power, also practically absolute in te-
tanus and diphtheria, is only absolute when applied
early in the course of the infection; that the quantity
of antitoxin necessary for prophylaxis or cure corre-
sponds to the quantity of toxin to be antagonized, and
finally, clinically considered, the longer the infection
has run and the more pronounced its character, the
larger is the dose of antitoxin necessary for cure.

Many questions have, of course, been raised as to
the limitations of the serum treatment and its possible
immediate or-remote dangers. These questions will
require for their solution painstaking, accurate and
unprejudiced study, and we may be sure that the in-
exorable logic of time will give us the answer.

We have now passed through the period of acute, .
intense interest: A world-wide experience with the
treatment has furnished the foundation for the neces-
sary debate over the meaning and plan and value and
limitations of the therapeutic revolution which seems
upon us. We are now ready to settle down to a ju-
dicial frame of mind, to watch calmly the develop-

ESSAYS ON BACTERIOLOGY. 87

ment of events, and to do our part in the coming work.
To this end two or three things are necessary:

First. Remembering that this new principle will
doubtless be brought forward and is being brought
forward in the treatment of other diseases, we must
guard against hasty enthusiasms based upon insuffi-
cient scientific experiment, and we shall certainly
have to guard against its commercial exploitation.
Already, unless the signs are misleading, the latter
evil is beginning to show itself. Plausible discover-
ers, with proprietary medicine schemes behind them,
may create some stir among the unwary, for the nos-
trum business is at present flourishing even in the
profession. But surely there ought not to be much
difficulty in distinguishing science from mercenary
trickery.

Second. We must expect and welcome and aid
scientific investigation and experiment along these
lines so clearly indicated as lines of progress.

Third. We must, while this whole matter is, as it
is, in the experimental stage, keep a clear view of the
facts, discriminating between things which are theo-
retical, uncertain and experimental, and those which
are demonstrated beyond question. Speaking again
of diphtheria only, the following seem to be the dem-
onstrated facts which we must accept: That there
is in this disease a germ which, being inoculated into
animals, will kill them. That this germ, being arti-
ficially cultivated, gives rise to a toxic substance or

88 ESSAYS ON BACTERIOLOGY.

substances, which also will kill. That this germ or
this toxin, being introduced according to a certain
method and in progressive quantities into certain ani-
mals, there is developed in those animals a progres-
sive resisting power to the germ or toxin, reaching an
astonishingly high degree, and lasting for a varying
but usually limited time. That the transfer of the
blood-serum of such animals to those previously sus-
ceptible to diphtheria does afford them almost at once
a practically absolute, though temporary, immunity
against or cure of diphtheria. ‘That, in a word, it is
thus possible to absolutely control otherwise fatal ex-
perimental diphtheria intoxication and diphtheria in-
fection in animals, and that without apparent harm.
That the longer the infection has run, the less certain
are the results, a point finally being reached when the
treatment may become impracticable and of little
avail. Experience with this treatment, applied to ac-
cidental human diphtheria, seems to indicate that hu-
man beings and the lower animals react in the same
way to the antitoxin serum therapy. But the truth
of this proposition is still to be fully and finally dem-
onstrated. We must wait for the verdict of time be-
fore we can say of men as of animals: We know that
a specific for diphtheria has been found. While we
wait for and help to hasten the solution of the ques-
tions, let us hopefully keep in mind a clear view of
the established facts.

VIII.

SERUM THERAPY IN DIPHTHERIA
‘AND OTHER DISEASES.

HE passing year has been prolific of investigations
and progress in the broadening field of bacteriol-
ogy. More and more we see the study of the disease
germs resulting in additions to our knowledge of diag-
nosis, treatment and prevention of the infectious proc-
esses. It is becoming more reliable and relied upon,
in clinical as well as pathological diagnosis. It is be-
coming a more and more important part of sanitary
science and preventive medicine. In the field of
therapeutics it is opening up lines of investigation and
experiment which are full of promise. No intelli-
gent person any longer looks upon bacteriology as a
fad or fashion. It has become in a hundred ways too
well established and of too much practical value for
any such view.

A year ago the subject of the antitoxin treatment
and serum therapy was attracting universal attention
and interest. Every one was watching it and eagerly
asking what was to come of it. This interest, though
quieter, is none the less intense, and current medical
literature has fairly overflowed with discussions upon

89

90 ESSAYS ON BACTERIOLOGY.

the new treatment as applied to several diseases,
chiefly to diphtheria. It may be helpful to sum-
marize briefly the best present views upon this subject.

First, then, it appears to be generally agreed that
diphtheria is a specific disease, due to a specific and
recognizable microbe. The methods of recognizing
and identifying this microbe have been well worked
out, and it has therefore come to be relied upon as the
most valuable because most positive means of diag-
nosis. The germ of diphtheria is one easily culti-
vated, and growing rapidly as it does, under proper
conditions, its recognition may be made the basis of
diagnosis for practical purposes. Diphtheria being a
dangerous disease in a community, and its identifica-
tion being of so much importance, health boards have
in increasing numbers equipped themselves for doing
this work in the interest and for the protection of the
public health. Already at least two cities in Indiana
have well-established departments in which the bac-
teriological diagnosis of diphtheria is made, and their
results agree with those in other cities in testifying to
its value and accuracy. No practicing physician who
has once had within his reach and has made use of
these aids to aceuracy in his work will fail to appre-
ciate the comforting assurance of their presence. No
physician who has a few times experienced the relief
of anxiety and uncertainty in doubtful cases will fail
to acknowledge himself and his patients debtors to the
science of bacteriology. -

ESSAYS ON BACTERIOLOGY. 91

Second, the ‘long-debated question of the relation-
ship of diphtheria and membranous croup has been
approaching a solution upon a basis which appears to
be reliable. It does seem as though we should soon
have a definite and positive answer to this vexed ques:
tion. Extensive and accurate investigations have
clearly proven that a large proportion—about 80 per
cent.—of the cases ordinarily reported as membran-
ous croup are membranous laryngitis,’ due to the
poison of diphtheria. Acting, as they must, upon
this demonstration, health boards are now coming to
be almost unanimous in requiring a report of such
cases, and in dealing with them as diphtheria. The
presumption must be that at least the great majority
of them are diphtheria. Clinical features, which
still seem to sustain the doctrine of duality, there may
be in some cases; but when from many of even such
cases the microbes of diphtheria are obtained and be-
ing cultivated and inoculated, show their infectious
quality, then, in the language of Virchow, as applied
to antitoxin, theories must give way to the brute force
of facts. Physicians, therefore, whatever their indi-
vidual views as to membranous croup, should recog-
nize the force of the facts, and should cheerfully sup-
port the health boards in following the course which
is evidently the one of wisdom and safety.

At the same time it is to be said that, just as there
are now known to be cases of membranous pharyn-
gitis resembling diphtheria, but not due to the diph-

92 ESSAYS ON BACTERIOLOGY.

theria germ, so there may be, and probably are, cases
of membranous laryngitis non-diphtheritic in charac-
ter. And so the old question is not yet fully settled.
The immediate future, we can hardly doubt, will
bring the full and satisfactory solution.

As to the antitoxin treatment of diphtheria, the
writer feels disposed to give it a large place, since it
belongs now to both bacteriology and clinical medi-
cine, though entirely an outgrowth of bacteriology.

In a former address emphasis was laid upon the im-
portance of getting a clear view of the established
facts as distinguished from the theories, and of keep-
ing these facts in mind as a guide to right-thinking
and acting. At that time the things which we seemed
warranted in accepting as demonstrated were these:
that there is a germ in diphtheria, which, being inocu-
lated in pure cultures, will kill; that this germ, being
artificially cultivated, produces an intense poison
which will kill; that, by the injection of gradually in-
creasing quantities of this toxin into certain animals,
they may acquire an enormous resisting power to it
and to the germs; and that by the transfer of their
blood serum this resisting power might be transferred
for a limited time to other animals, and be for them
an almost specific preventative of diphtheria and al-
most equally specific cure of the disease in its earlier
stages. These, which seemed worthy of acceptation
as demonstrated facts, remain as they were, though
their explanation still eludes us.

ESSAYS ON BACTERIOLOGY. 93

The chief theories in explanation of these facts are
two: first, that there is in the antitoxin serum a sub-
stance which directly antagonizes the growth of the
germs or neutralizes the toxin, or both; second, that
its action is biological, rather than chemical, stimu-
lating the body to an increased resistance. There are
strong arguments in favor of each view, but we are
not yet in a position to decide the question.

Meantime, the treatment has been applied in many
thousands of cases, and what of the results? Statis-
tics from many sources have been and are constantly
being published, and of their value and significance
others are as capable of judging as the writer. It
must.be said that the weight of opinion is in favor of
the treatment. Certainly the majority of those who
have used it extensively believe it to have given re-
sults surpassing those of anything heretofore known.
Perhaps the-best summary of the whole matter is that
published by Welch, of Johns Hopkins University,
and widely quoted. His conclusions are that the anti-
toxin is of great value, is comparatively harmless, and
that it is our duty to use it. As a matter of record
the following extract from Dr. Welch’s paper is here
given place:

In Dr. Welch’s contribution, an analysis of 7,166
cases of antitoxin-treated diphtheria is reported from
the hospitals of Germany, France, Austria and Amer-
ica. From a careful study of these cases, and from a
thorough sifting of all the evidence, the figures show
a mortality of 17.3 per cent.

94 ESSAYS ON BACTERIOLOGY.

Alongside of these cases, and in the same hospitals,
with the same favorable surroundings, 5,706 cases of
diphtheria were treated by the old method, with a
death-rate of 42.1 per cent.

“There was, therefore,” says Dr. Welch, “an appar-
ent reduction of case mortality by the use of antitoxin
of 55.8 per cent.” ,

Statistics, according to the age of the patient, both
with and without the serum treatment, afford very in-
teresting reading.

From a summary of this table, Welch says: “Of
1,729 cases of diphtheria with a fatality of 14.9 per
cent., 1,115 cases treated with antitoxin during the
first three days of the disease yielded a fatality of 8.5
per cent., whereas 546 cases.in which antitoxin was
first injected after the third day of the disease yielded
a fatality of 27.8 per cent.

“Of 232 in which treatment was begun on the first
day five died, or 2.15 per cent. Of 492 cases in
which treatment was begun on the second day 30
died, 7.7 per cent. Of 331 cases in which treatment
was begun on the third day 43 died, 13 per cent.; on
the fourth day 19 per cent., on the fifth day 29.3 per
cent., on the sixth day 34.1 per cent.”

In closing his report Dr. Welch makes this state-
ment: “The principal conclusion which I would
draw from this paper is that our study of the results
of the treatment of over 7,000 cases of diphtheria by
the antitoxin demonstrates beyond all doubt that anti-

-ESSAYS ON BACTERIOLOGY. 95

diphtheritic serum is a specific curative agent for
diphtheria, surpassing in its efficacy all other known
methods of treatment for this disease.”

There are occasional unpleasant effects in the form
of more or less intense erythema, sometimes with
fever, severe pains, glandular swellings, and even
effusions into joints or serous cavities. A few serious
accidents and even deaths have followed the antitoxin,
and apparently due to the injections. Just what these
accidents mean, and whether they are inseparable
from the antitoxic serum, we do not know, but they
serve to make us properly cautious, and warn us not
to accept too readily the assurance that, even under
the most extreme precautions of preparation, such an
agent is always and wholly free from danger. The
good appears to overbalance any evil, but we are not
yet sure that.there is no possibility of harm.

Diphtheria is not the only disease in which anti-
toxic serum therapy has been applied. The princi-
ples of production and use being established, the en-
deavor is constantly being made to extend its sphere.
Indeed, the tetanus antitoxin preceded that of diph-
theria, and in animals experimented upon in the lab-
oratory seems to have been equally successful. For
obvious reasons, however, its clinical application has
not been as extensive nor apparently of as much value.
A tetanus antitoxin is now within the reach of phy-
sicians and is certainly worthy of trial, at least in the
early stages of lockjaw. According to all who have

96 ESSAYS ON BACTERIOLOGY.

had experience with it, it must be given in large doses
and as early as possible in the disease. If possible, it
should be used as a preventive after a suspicious
injury.

For pneumonia, typhoid fever and tuberculosis,
antitoxic serums have been prepared and have been
used in a considerable number of cases, and in several
other diseases they have been and are being tried to a
limited extent. It is too early to form any reliable
opinion as to the value of the treatment in these dis-
eases. The serum treatment of tuberculosis has been
given a sufficient trial to indicate that, as at present
prepared, not much can be expected from it.

As to tuberculosis, the greatest of the serious dis-
eases with which we have to deal, each passing year is
bringing out in bolder lines the proof of its infectious
character. Personally, the writer grows more and
more convinced of the truth of this view, and of the
importance of action based thereupon. Of this he
has something to say elsewhere. _

Cholera has been the subject of a large amount of
investigation, the result of which has been to empha-
size its water-born character in many if not most in-
stances, and to make easier and more reliable the bac-
teriological diagnosis. The preventive inoculations
against cholera have been carried out upon a larger
scale by Haffkine in India. His recent report is a
model of scientific spirit and work, and appears to

ESSAYS ON BACTERIOLOGY. 97

justify a hopeful view of the measure. His investi-
‘gations will be continued under government aid, and
we shall look with interest for the publication of re-
sults from time to time.

The injection of the erysipelas toxin in malignant
disease has been continued by many observers in this
country and in Europe. It still appears from this
experience that the treatment does have considerable
retarding or curative effect in sarcoma, but little if
any in carcinoma. In general, however, there seems
to be less promise in the measure than a year ago.

The influenza bacillus seems to have established it-
self in the opinion of most bacteriologists as the true
germ of la grippe, and several observers have ex-
pressed a high opinion of its diagnostic value.

- The subject of cancer and its possible microbic ori-
gin has engaged the attention of many investigators,
and various claims to a discovery of the specific caus-
ative agent have been made. But most of the so-
called cancer germs have been shown to be only bodies
appearing during and resulting from the normal or
abnormal cellular changes which occur in or about
the growth. The germ of cancer, if such exist, has
not yet found an established place in bacteriology.
From the far west, from the rising empire of Japan,
comes the news confirming that announced before,
that Kitasato had discovered, cultivated and proven
the specific character of the microbe of the bubonic

98 ESSAYS ON BACTERIOLOGY.

plague, which has raged in China during the last two
years. And thus another mark of honor has been
won by the already famous Japanese, who a few years
ago was a favorite pupil and assistant of Koch in Ber-
lin. And thus, too, peace and science have their vic-
tories there as well as war.

TX.

THE POSITION OF VACCINATION IN
PATHOLOGY AND BACTERIOLOGY.

T is not the chief purpose of this paper to enter into
a direct argument upon the protective influence of
vaccination against smallpox, nor to array the statis-
tics in its favor. Such an effort would surely be su-
perfluous. He who in this day, with the light of the
last decade’s revelations before him, issues broad de-
nials of the efficacy of vaccination, seriously compro-
mises his reputation for professional and scientific
sanity. It were useless to argue with him. But in
view of the recent advances in our knowledge of the
infectious diseases, and the efforts being made to ex-
tend the range of preventive and curative inocula-
tions, it may be of interest and profit to survey the
field and see just where vaccination against smallpox
stands in pathology, what it means, its extent and lim-
itations, and what its promise for success in other dis-
eases.
Two theories have always existed, and do, to some
extent, still exist, as to the nature of cowpox. The
one, that it is a peculiar, distinct disease, whose antag-

99

100 ESSAYS ON BACTERIOLOGY.

onism to smallpox is likewise a peculiar, isolated fact,
an exotic in the field of pathology. The other, that
it is simply smallpox in the cow, and vaccination sim-
ply the induction of a modified form of smallpox.
Either of these theories might be true and yet the pro-
tective influence of vaccination not excite, in this day,
great incredulity among scientific men. For, sup-
posing the former theory correct, it has been shown
that there is an antagonism between certain distinct
bacteria, an antagonism so pronounced as to be inhib-
itory or destructive. ‘Thus the intensely malignant
anthrax is prevented or arrested by simultaneous inoc-
ulation with the comparatively harmless bacillus pro-
digiosus. There are other antagonisms of a similar
character, though perhaps none equally striking. It
is, therefore, quite within reason, and within the
sphere of analogy, to suppose that cowpox, being a dis-
tinct disease, might protect from smallpox.

But credible though it may be, and quite within
the range of possibility, there seems really little now
left in support of this theory of cowpox. The facts
of nature, i. e., the natural history of cowpox, the in-
creased knowledge of recent years in the whole field
of bacterial pathology, and direct experiment, com-
bine to strengthen the view that cowpox is simply
bovine smallpox.

If this is true, the whole matter becomes a simple
one.

Discovered accidentally, but worked out by the

ESSAYS ON BACTERIOLOGY. 101

painstaking and lifetime devotion of Jenner, and to
his immortal renown, vaccination was for a long time
thought to oceupy a peculiar and isolated place in
pathology. The mystery about it, and that which
strengthened incredulity as to the identity of cow-
pox and smallpox, was this:—how can such a virulent
disease as smallpox be so modified and mollified by
passing throngh the body of the cow? For such a
thing there was no analogy.

But the investigations of the last ten years have
put an entirely new face upon this idol of unbelief.
The modification of a disease by passing it through
the body of certain animals has become a common-
place matter in pathology. We no longer wonder at
such a claim nor doubt its possibility.

It is unnecessary to enter into the details of these
new facts, they are so generally known. It is suffi-
cient to refer to the modification of the virus of ra-
bies, of the pnenmococcus and of others, brought
about by this means, or by other methods of altering
the culture soil or the conditions of growth.

Acting upon the view that cowpox was modified
smallpox, the attempt has been repeatedly made to
imitate the whole process artificially; that is, to secure
vaccine virus by inoculating the cow with smallpox.
The first to do this is supposed to have been Gassner
of Gunzburg (1807). It was done on a large scale by
Thiele of Kasan and Ceely of England (1838). They
carried their vaccine virus, thus obtained, through

102 ESSAYS ON BACTERIOLOGY.

sixty to seventy generations in several thousand per-
sons, and subsequently proved its efficiency by re-
peated inoculations with genuine variola humana.
(Whittaker.) Similar experiments were made by
Badcock and Senfft. The committees of Lyons (1865)
and Turin (1874) opposed these conclusions, but they
failed to explain the facts. The whole subject has re-
cently been gone over by an English experimenter,
who shows how these committees: were misled, and
claims to have finally settled the matter.

We have doubtless something still to learn about
the methods of securing vaccine matter by the inocu-
lation of animals with human variola. Perhaps the
best results will only be got by using other animals
as well as the cow; perhaps we shall have to wait for
the discovery of the smallpox germ and the more ex-
act experiments which would follow. In the mean-
time we must admit the strength of the evidence that
cowpox is a modification of smallpox, and that vac-
cination is simply variolation in mild and modified
form; that it is inoculation stripped of its virulence
and dangers. .

Vaccination, in the light of modern knowledge,
takes its proper place, falling naturally and easily un-
der the sway of those principles which rule in the field
of pathology in which it belongs.

What are some of these principles revealed by a
study of that great group of diseases, one attack of
which affords immunity?

.

ESSAYS ON BACTERIOLOGY. 108

First. The immunity or protection afforded by
one attack of a disease is not necessarily absolute.

Illustrations of this rule are met with in our daily
practice. Thus, we see those who have unquestion-
ably had cholera, typhoid fever or scarlatina, suffer-
ing from second or even third attacks. This is true
also of smallpox. Such experiences are exceptions,
rare exceptions with some diseases, but they occur
with sufficient frequency to warn us against too rad-
ical views of the value of acquired immunity, while
they in no way disprove the fact of such immunity.

Second. The protection afforded by one attack of
a disease is not necessarily permanent.

That the protective influence of the primary attack
fades with the lapse of time is, with some diseases, a
matter of common observation. The duration of the
immunity varies within wide limits. With some
maladies it is practically life-long; with others so short
as to be, to ordinary experience, hardly discernible.
The difficulty of defining these limits is increased by
the necessity of including in the calculation that pe-
culiar insusceptibility to certain diseases which seems
to be gradually and naturally acquired with advanc-
ing years. In this connection we must, however, not
forget the havoc wrought, even among the adult pop-
ulation, with the advent of a new disease. The Sand-
wich Islands were swept, as by a hurricane, by the
fatal breath of measles in 1848, while the Fiji Island-
ers fled in terror from its deadly presence.

104 ESSAYS ON BACTERIOLOGY.

Modern bacteriological experiment has stepped in
at this point to enlarge our knowledge, revealing the
fact that some diseases are followed by a period of
immunity, distinet, but so short-lived as to have es-
caped observation or demonstration. This seems to
be true of cholera. From such short periods we rise,
step by step, to reach diseases like measles, scarlatina,
typhoid and variola, the protection of which usually
extends over such a time as spans the ordinary dura-
tion of human life. Fortunate it is that immunity
is so often long-continued. Yet the fact remains that,
as a general rule, with passing years its energy declines.

When we come to apply this rule to vaccination, we
shall see how the recognition but misunderstanding of
it at one time threatened to wreck that life-saving -
agency.

Third. Quantity and quality of the virus, or vigor
of the attack, is an important factor in the immunity
which shall follow.

It is a common opinion, both professional and pop-
ular, that those who have experienced mild attacks of
a disease are more liable to recurrence than those in
whom the attack has been pronounced. Laboratory
experiment has again stepped in here with a contribu-
tion of more exact knowledge. It has been abun-
dantly shown in the laboratory, where the conditions
can be so thoroughly controlled, that the quantity
and activity of the virus or other protective agent
stand usually in direct ratio to the immunity which

ESSAYS ON BACTERIOLOGY. 105

such treatment affords. Thus Pasteur’s first vaccine
affords but feeble protection, the second vaccine in-
creases the security; and so advancing, step by step,
from weaker to stronger virus, practically absolute
protection against rabies is secured to animals.

Fourth. The protection afforded by one attack of
a disease is a positive, an active thing; it is an endow-
ment with a new power.

He who has not had measles, scarlatina nor variola
is susceptible to those diseases. In no other known
way can he obtain an immunity. If this statement
seems trite and unworthy of the prominence here
given it, the justification will be found in its impor-
tant bearing upon the practical application of vaccina-
tion.

If now these principles are correct, they ought to be
applicable to vaccination.

First, we should not expect the protection thus af-
forded to be absolute. Experience alone could decide
the matter. And experience leaves us with a trifle of
uncertainty, because the immunity approaches so near
to completeness that we can but suspect that the few
exceptions are only apparent and due to some defect
in the vaccination. Those few persons who have had
variola ‘within a few years of vaccination may and
probably have not had a genuine inoculation with
cowpox. But, it need hardly be said, the departure
from complete protection is so slight as to be of small
practical moment.

106 ESSAYS ON BACTERIOLOGY.

Second, we should not expect the protection of vac-
cination to be permanent; certainly not in view of the
fact that unmodified smallpox itself does not always
afford permanent safety. Jenner himself erred at

‘this point, believing that cowpoxing protected for life,
and we can easily understand how he made this mis-
take. With the light of modern knowledge, still
more with the light of a century’s experience before
us, we can easily pardon an error into which he fell
simply from lack of experience which could only come
with the lapse of years. He did not live long enough
to get a final view of the matter. When, with pass-
ing years, some of those who had been vaccinated be-
gan to show a susceptibility to smallpox, and the truth
which is so clear to us began to force itself upon the
world, it came with such a shock as almost to threaten,
as I have said, the ruin of vaccination. The suspicion
arose and was industriously fostered that the whole
thing was a gigantic and astounding delusion. For-
tunately, calmer minds saw the true state of the mat-
ter, with the result that the necessity for and the prac-
tice of re-vaccination became established.

While it is evidently impossible to fix upon a time
at which the efficacy of vaccination has declined to the
danger point, there is a substantial agreement among
all authorities which, being acted upon, leads to al-
most assured safety. The German statistics thor-
oughly and accurately collected seem to show that no
case of smallpox has occurred in that country within

ESSAYS ON BACTERIOLOGY. 107

ten years of a successful vaccination. This is com-
ing to be accepted throughout the world as the basis
for the regulation of re-vaccination. If all children
were vaccinated within the first and at the tenth year
of life, smallpox would be practically abolished, as in-
deed it has been from those communities in which this
rule is followed.

Third, we should expect the thoroughness of the
vaccination to stand in something like a direct ratio to
the degree of protection. And this we certainly find
to be true. The experience in every outbreak of
smallpox confirms this rule. And the lesson of it is
obvious: we should vaccinate thoroughly, knowing
that the result will be a proportionate thoroughness of
protection. We wrong those who commit this mat-
ter to our care, and wrong the public, by failure to
appreciate and act upon this too much neglected
truth.

Fourth, the protection afforded by vaccination is a
positive, an active thing; it is an endowment with a
new power, conferred upon the individual and to be
obtained, so far as we know, only in this way. He
who has not had variola is susceptible to that disease
unless properly vaccinated. And that vaccination
should be genuine.

The protection comes, not by the scarification and
its resulting lesion, not by the scarification and the
application of vaccine lymph; but by the successful
induction of the specific lesions of vaccinia, and the

108 ESSAYS ON BACTERIOLOGY.
& i

vaccinator should see to it that this is secured or the
procedure repeated. Many of those said to have been
vaccinated have doubtless not been really vaccinated
at all. Thus, in the presence of smallpox, discredit
is thrown upon vaccination and danger upon the com-
munity.

The public should be made to understand this: that
the vaccinator should have full opportunity to insure
genuine vaccinations, and that the security arising out
of the now comparative rarity of smallpox may be a
false security unless reinforced by genuine, general,
and repeated endowment with that active power of re-
sistance which can come only in one way.

In a word, the public should distinctly understand’
that the immunity through vaccination, though prac-
tically complete, is temporary and must be reinforced
by repetition; that the process must be genuine, and
that, somewhat unpleasant though it may be, it should
be thorough. With these injunctions may happily be
joined the assurance of safety by their observance.

In conclusion, something ought to be said, from a
pathological standpoint, about the supposed dangers
of vaccination. Whatever ground there may have
been for fear in its earlier history, when the human
lymph was indiscriminately used, vaccination as at
present practiced is attended by but trifling danger.
Outeries to the contrary, with the wild ‘statements
which sometimes accompany them, are but the wan-
derings of distorted vision and disordered minds.

ESSAYS ON BACTERIOLOGY. 109

The dangers of vaccination, such as there are, arise
from four sources:

1. The induction of a very mild infectious disease.

2. The transfer of human disease by the use of
human lymph. Of these syphilis is the most to be
feared. There are others, but of much less impor-
tance. This is avoided by the use of animal virus.

3. The possible transfer of diseases to which the
animal is subject. Among these, theory, or more fre-
quently perhaps imagination, suggests many; facts
point to but few, such as erysipelas and suppuration.
This danger is reduced to almost nothing by proper
care in the management of the vaccine stables.

4, The vaccination wound may become infected,
as may any other trifling abrasion. Suppuration or
erysipelas may supervene and cause trouble, but the
avoidance of these complications is so plain and sim-
ple, in this day of surgical cleanliness, as to hardly
need mention.

There remains, perhaps, after all, a minute but real
danger, which, though not for a moment to be placed
in the balance over against the incalculable good,
cannot be finally ruled out till the discovery of the
specific bacteria of vaccination enables us to handle
and apply the virus with the exactness of a chemical
experiment. In the meantime we may rest assured,
and may assure the public in whose interests alone we
are working, that the dangers of vaccination are to-
day almost entirely imaginary and hardly worth more

110 ESSAYS ON BACTERIOLOGY.

than a passing thought, and are chiefly of historical
interest. For the distorted and extreme statements
which are sometimes issued, there is, in the face of the
plain facts of experience and of science, no excuse.
It is hardly too much to.say that they are a criminal
abuse of privilege.

In this day the public has not the fear of smallpox
before its eyes as formerly. It forgets too easily.
We have no realizing sense of its horrors. Therefore
we see growing a false sense of security and a growing
carelessness in regard to the necessity and the means
of insuring safety. If we will only follow the plain
teachings of that which has now become an integral
part of biological science, availing ourselves of the
equally plain lessons of experience in its application,
we need have no fears of the “stinking pestilence”
which struck terror to the hearts of our forefathers.
The truth is before us, and the truth will make us
safe. If we grow too careless, indifferent and neg-
lectful, history may repeat itself in giving another
and a different lesson from experience.

From such a lesson we may well pray, in the name
of Jenner, to be delivered.

XK.

BACTERIA, AND BACTERIOLOGICAL
METHODS AND DIAGNOSIS.

ACTERIA are minute cells, classified biolog-

ically far down the line in the vegetable king-
dom.” They vary much in size, but all are so small as
to be beyond the range of unaided vision. An or-
dinary-sized bacterium would be one ten-thousandth
to one twenty-thousandth of an inch in diameter or
length. When seen singly, they are practically color-
less, but many bacteria, when growing in masses or
colonies, present distinct and even brilliant colors.
Such colonies often resemble, in gross appearance, the
ordinary moulds.

While bacteria are so numerous and widespread as
to be commonly said to be ubiquitous, it is not true,
as many believe, that the air is swarming with them.
Like all bodies of greater specific gravity than air,
they tend to settle, so that the quiet atmosphere in
many places is comparatively free from microbes.
Exposed waters, the surface and the upper layers of
the soil, and the surfaces of solid bodies generally,
harbor bacteria in large numbers; but the deeper

111

112 ESSAYS ON BACTERIOLOGY.

layers of the soil, the waters from clean springs, and
deep wells free from surface drainage, are compara-
tively or quite sterile. The unexposed tissues of
healthy bodies are also normally free from germs.

Though it is now known that many diseases are
caused by bacteria, it must not be supposed that all
the bacteria are enemies of the higher forms of life.
On the contrary, many of them play a beneficent role
in promoting the disintegration of dead organic ma-
terial, which would otherwise, by accumulation, make
the world one vast graveyard; in preparing, by such
changes, the food for other living beings, and in ren-
dering the soil suitable for the growth of higher
plants. We fear the microbes which produce disease,
yet life would soon be impossible to higher organisms
without the helpful work of others. In all our study
of bacteria let us not forget that they may be the
friends as well as the enemies of mankind. It is, how-
ever, the disease-producing micro-organisms which en-
gage the chief study of the physician, for these it is
with which he has to contend. These it is of whose
presence he must learn, in the field of diagnosis, to be
forewarned.

The bacteria, like other living things, perform the
ordinary functions of life. They breathe; they eat,
taking in food substances, changing, digesting and ap-
propriating them to their needs, excreting the waste
products. They multiply and reproduce their kind.
Like other living beings, also, their existence, and

ESSAYS ON BACTERIOLOGY. 113

especially their growth and multiplication, is chiefly
under the control of four factors, namely, food, tem-
perature, moisture, and the presence or absence of air.
And again like most other living beings, the evidence
of their activity is not chiefly mechanical, but is found
in the field of biological chemistry.

Many bacteria grow at the ordinary temperature
of the house or the surrounding air, while some re-
quire for their multiplication temperatures approxi-
mating that of the bodies of warm-blooded animals.
They do not multiply in the dried state, being in this
respect again like other seeds. Some require while
some reject a free access of air. Some welcome while
some quickly die under direct sunlight. Indeed, the
more we study them the more clearly do we see that
they are under the laws which prevail throughout the
organic world.

The attempt to classify the bacteria on a strictly _
scientific, that is, a botanical basis, has thus far been
unsatisfactory. They are therefore classified accord-
ing to certain of their more conspicuous characteris-
tics. Of these groupings the most common, and the
one generally used, is that based upon their form.
According to this. system we describe most bacteria as
belonging to one or the other of three great groups.
These are: the round organisms or micrococci, the rod-
shaped organisms or bacilli, and those having a spiral
or corkscrew shape, called spirilla. Thus we speak of
the micrococci of erysipelas, the bacilli of diphtheria,

8

114 ESSAYS ON BACTERIOLOGY.

and the spirilla of cholera. The term bacterium,
though originally given to the rod or staff-like forms,
has now come to be applied to micro-organisms or
germs in general.

Another important classification of bacteria is based
upon some marked biological property or activity.
Thus are described the color-producing or .chromo-
genic organisms; the saprophytes, or those which live
upon dead organic material; the saprogenic or putre-
faction-producing bacteria; the zymogenic or ferment
producers, and hence the old term zymotic or ferment
diseases; and finally, to the physician the most im-
portant of all, the pathogenic or disease-producing
microbes. Flourescent and phosphorescent bacteria
are also described. ‘These terms and groups are not
mutually exclusive, since, for example, bacteria may
be pathogenic and at the same time chromogenic or
color-producing. According to their ability to grow
with or without free oxygen, micro-organisms are also
said to be aerobic or anaerobic, a classification of great
practical as well as scientific importance.

Many, perhaps most, bacteria are motionless, save
for a fine vibratory activity, the molecular or so-called
Brownian movement. Others have the power of true
locomotion, due to vigorous contractions and’ expan-
sions of their bodies, or to the possession of minute
appendages called flagella. At best, however, the
sphere of such locomotion is limited, and does not con-
fer the power of passing over great distances. Any

ESSAYS ON BACTERIOLOGY. 115

considerable niigration of bacteria within the body is
brought about only by transport through the various
body fluids.

Bacteria multiply by the process of fission or split-
ting, one cell, by this simple process, giving rise to
two, four or more daughter cells, which have or soon
assume all of the properties of the parent. In addi-
tion to this process of splitting, they reproduce them-
selves by spore or seed formation, one cell giving rise
to one spore, the latter proceeding at once to develop
into a mature bacterium, or lying dormant until the
conditions for its full development are present. Asa
rule, these spores are much more tenacious of life than
the mature bacteria, are much more resistant to hos-
tile influences, and therefore more independent of
their environment. For these reasons spores will
often resist drying, and degrees of cold and heat, even
to freezing, or boiling for a time, such as would rap-
idly destroy the fully developed organisms. In this
spore stage, bacteria, like other seeds, may frequently
retain their life, while not growing nor mutiplying,
for long periods. Such facts often explain the in-
sidious persistence of infectious material even under
apparently adverse conditions. The seeds of various
grains lie dry and ‘cold in the'bin during the winter,
ready to sprout with the advent of spring. And. so
with the seeds of disease.

Various theories have been proposed to explain the
disease-producing activity of micro-organisms. Most

116 ESSAYS ON BACTERIOLOGY.

of these theories have some measure of truth, but all
have failed, until recently, to explain the facts. The
problem has now been worked out to a fairly satis-
factory conclusion in the establishment of the toxin
theory. We now know that most of the results ‘of
bacterial action are explained by the production in
the course of their growth of certain new substances.
If these substances are injurious or poisonous to the
living body, the bacteria producing them are said to
be toxic; if they are produced during the growth of
the microbes within the living body, such microbes
are said to he infectious. If the toxin-forming organ-
isms are regularly associated as causative agents with
a peculiar or specific disease, they are called specific
bacteria. Thus the definition and classification of
many diseases has become more accurate, more ra-
tional, because built more nearly upon the basis of
causation. Infectious diseases are those which are
caused by the presence and growth, within the body,
of living producers of poisons. Specific infectious
diseases are those each of which is caused by a par-
ticular living toxin-producer, a particular or specific
bacterium. For example, the condition commonly
known as blood-poisoning may be due to any of a
number of bacteria, while the peculiar and specific dis-
ease diphtheria, with its peculiar poisoning of the
blood, is believed to be caused by the specific diph-
theria bacillus alone. An important corollary to such
a doctrine is found in this: that if, for example, the

ESSAYS ON BACTERIOLOGY. 117

latter statement is true, we have in the detection of
the diphtheria bacillus a positive means of recogniz-
ing or diagnosing diphtheria, and we at once begin to
see how the science of bacteriology becomes a part of
everyday practical medicine.

Bacteriology has entered into and become a work-
ing part of practical medicine in several ways. It
suggests and directs general preventive measures
against the infectious diseases. It suggests and
guides preventive and curative measures in individual
cases; and it is affording us more accurate and more
rapid means of diagnosis in an increasing number of
diseases. It is therefore becoming of importance to
every practicing physician, and of interest to every in-
telligent person, to know something of the methods of
bacteriological work, especially of that part of it
which is applicable in the working laboratory—that
is, in the consulting room of the doctor. The more
this work is studied the more will it appear that it
follows in many respects the principles and methods
of ordinary agriculture. Keeping this fact in mind,
many otherwise strange things become clear and
simple.

The cultivation of bacteria has, mainly through the
efforts of a few great men like Pasteur and Koch, be-
come a comparatively simple matter, now taught in
every well-equipped medical school. In the earlier
days it was customary to cultivate bacteria in fluids,
such as beef broth. But with this method it is diffi-

118 ESSAYS ON BACTERIOLOGY.

cult to separate the different varieties which grow in
confusion in the liquid. The invention by Koch of
the solid culture soil has made the separation of micro-
organisms rapid and, as a rule, easy. The substances
used for this purpose have been many, but experience
has singled out a few which answer all ordinary pur-
poses. The simplest of these is the surface of a
cooked potato, upon which many bacteria may be sat-
isfactorily grown. But the potato has been largely
superseded by culture soils or media having an al-
buminous basis, such as that derived from meat. In
order to solidify this meat extract or bouillon, about
10 per cent. of gelatin is added, giving a clear, firm
product, the beef-gelatin soil. But since gelatin soft-
ens at the body or incubator temperature, it has in
recent years been improved upon by the use of an
Asiatic sea-weed called agar-agar. "This substance, of
which about 2 per cent. is added to the bouillon, gives
us the now widely used beef-agar culture medium,
having the great advantage of remaining solid at the
heat of the body and of the incubator. It therefore
serves for the cultivation of bacteria which require
such temperatures for their successful growth. In
order to retain as much as possible of the albuminous
constituents of the beef after the repeated heating
necessary in its preparation, it is either peptonized or
artificially digested, or pre-digested albumen in the
form of peptone is added. IE to this peptonized beef-
agar 4 or 5 per cent. of glycerin be added, its field of

ESSAYS ON BACTERIOLOGY. 119

usefulness is widened, since upon this medium will
grow well certain bacteria which grow but indiffer-
ently or not at all wpon the simpler soils.

In his researches upon the tubercle bacillus Koch
brought forward solidified blood-serum, which has
proven the most valuable culture medium for some of
the sensitive or the strongly parasitic microbes. Ii
was upon this substance that he was first able to grow
the germ of tuberculosis, and, as a result, to work out
the perplexing problem of the cause of this disease.

Certain fluids obtained from the living body are
sometimes used alone or in combination as culture
media. Such are the liquid exudates in cases of
pleurisy, peritonitis, or other inflammations of serous
membranes. Finally, the living body is itself made
to do service as a laboratory for the growth of bac-
teria, thus imitating exactly the natural process.

Of all of these substances, those most frequently
used are the glycerin-agar, and the solidified blood-
serum, either pure or variously modified. The blood-
serum and agar are often combined with happy results.

In all culture work absolute sterilization of ma-
terials and instruments is necessary, lest slight con-
tamination at the beginning grow into gross and mis-
leading contamination at the end. If we are to in-
terpret correctly the final findings, we must know with
certainty the beginning. There must be in our final
cultures no bacteria except those placed. there at the
start.

120 ESSAYS ON BACTERIOLOGY.

The sterilization of culture materials and apparatus
is accomplished by heat, either dry or moist, accord-
ing to the character of the substance to be sterilized.
For this purpose two pieces of apparatus have come
into use: the steam sterilizer, similar to an ordinary
steam cooker, and the dry sterilizer, a simple portable
sheet-iron oven. The culture medium is placed in
sterilized vessels, usually ordinary chemists’ glass test
tubes, the mouths of which are tightly filled with
cotton, the latter having been previously subjected to
heat in the oven. Access of air is thus allowed, while
bacteria are effectually excluded. Open vessels,
which cannot be plugged with cotton, are placed un-
der a belljar inverted over a plate of glass, the whole
constituting what is called a moist chamber, in which
the growing cultures may be inspected. Other ves-
sels of special construction are used for special pur-
poses, but the test-tube method of culture is the one
followed in all ordinary work. If the tubes are to be
kept for some time either in the open air or in the in-
cubator, drying of their contents is prevented by rub-
ber caps placed over the cotton plug. The whole
process is indeed similar to that of cooking, sealing,
and thus preserving fruit. For the cultivation of
bacteria at the body temperature an incubating or
breeding oven is used, similar to, though more ac-
curately constructed than, the ordinary egg hatcher.
This apparatus is a double-walled, felt-jacketed oven,
the space between the walls being filled with water to

ESSAYS ON BACTERIOLOGY. 121

insure against rapid fluctuations of temperature. It
is heated by a self-regulating gas burner, so that the
temperature is maintained for days or weeks at the de-
sired point. Many bacteria which grow best and most
rapidly in the incubator may also be successfully
though more slowly and somewhat imperfectly grown
without, any special incubating apparatus, provided
the temperature be kept fairly near that of the body.

Inoculation of bacteria-containing material onto the
culture medium is usually made with a platinum or
other wire, sterilized before and immediately after
use by heating in a clean flame. In rapidity of
growth bacteria vary, like other seeds, and under sim-
ilar conditions. If the conditions are favorable, most
bacteria present visible cultures in from one to three
or four days. A few of the known varieties require
from one to three weeks for their development.

To illustrate the method of bacteriological investi-
gation in its simplest form, let us suppose that we wish
to discover the germ of diphtheria. Having prepared
the culture material and been assured, by protracted
observation, of its freedom from bacterial growth, we
take upon a sterilized wire from the throat a little of
the membrane presumed to contain the specific germ.
Removing for a moment the cotton plug from a tube,
this material is deposited in the previously warmed
and liquefied agar-glycerin. The contents of this
tube, or of another into which a portion has been
transferred from the first for the purpose of dilution,

122 “ESSAYS ON BACTERIOLOGY.

is now poured upon a sterilized plate of glass, where it
quickly hardens into a transparent film resembling
gelatin. Placing this plate in the moist chamber,
and enclosing the whole in the incubator, we await
the resulting culture. After some days we find the
plate studded with bacterial colonies of various ap-
pearance. Ocular and microscopic examination of
these colonies reveals the fact that several varieties of
microbes were present in the throat and are growing
on the plate. Repeating the procedure, we make
plate cultures from the different colonies, each suc-
ceeding experiment affording more nearly a pure cul-
ture of one variety. Finally, we reach, upon differ-
ent plates, pure cultures of each variety of micro-or-
ganism which grew upon the first plate. One of
these we presume to be the germ of diphtheria. We
now proceed to test the presumption. Animals are
inoculated with each variety of bacterium, the one
which produces diphtheria in the animal being now,
' with stronger conviction, believed to be the one sought
for. Carefully studying this germ and recording the
results of the study, we go back and repeat a number
of times the whole procedure. We examine many
cases of diphtheria and identify this germ in all. We
thus prove its constant presence in the disease. We
re-cultivate it and repeat many times the successful
inoculations, finding it always present in the artifi-
cially-produced disease; and thus we complete the
chain of proof and the identification of the germ of

ESSAYS ON BACTERIOLOGY. 123

diphtheria. Having done this, we are able to iden-
tify it at any time or placc, and, by recognizing it, to
diagnose the disease to which it belongs.

Were the attempt to identify the germ of each
specific infectious disease so easily carried to a suc-
cessful issue, little would now remain to be done in
this direction. Unfortunately, the task is not usually
so simple. Difficulties or temporary defeats are likely
to be met with at every step. To begin with, the ma-
terial taken from the throat, though containing vari-
ous bacteria, might not include the germ of diph-
theria. The final inoculation experiments would
therefore be negative. Or the culture soil might not
be suitable for this particular microbe, and again the
results would be negative. Unfavorable conditions,
such as the presence or absence of air, might defeat
the experiment; or the growth of one or more of the
other bacteria might obscure, retard or prevent the
growth of those sought for. Finally, though the de-
sired germ might be obtained in pure culture, the ani-
mals experimented upon might not be susceptible to
the disease in question, and again a negative or neu-
tral result would be reached. Here, therefore, as
in agriculture, though the general principles and
methods be simple, a reliable conclusion is to be
reached only by a successful management of details.
But having once identified a germ and demonstrated
its specific causative relation to a disease, its identifi-
cation and manipulation thereafter usually becomes

124 ESSAYS ON BACTERIOLOGY.

comparatively easy, and the way opens for experi-
ments with it in the direction of diagnosis, prevention
and cure.

It has already been pointed out that the explana-
tion of the disease-producing action of bacteria is to
be sought chiefly in their poisonous contents and
products. For the purpose of obtaining these poison-
ous products or toxins for experimental work, the bac-
teria, once obtained in pure cultures, are usually
grown in liquids. The bacteria are then filtered out
by porcelain filters, leaving a fluid containing the
toxin, which, representing the active principles of the
bacteria, may, for experimental purposes, be used in
exact dosage. Or, to more fully imitate nature, the
bacteria themselves, washed free from all extraneous
substances, may be pulverized and dissolved to ob-
tain their constituents. Here again, while general
principles and methods are simple, the details of suc-
cessful work are often many and perplexing. But
such difficult procedures belong chiefly in the experi-
mental laboratory; the culture work available and
useful to the practicing physician, following, as it
does, the paths laid out by the investigators, once
learned, is uncomplicated and easy.

The microscopic study of bacteria is an eeeednely
attractive subject to the physician, revealing a world
of curious and interesting things, and opening up a
most valuable field of diagnosis. Improvements in
the construction and manipulation of the microscope

ESSAYS ON BACTERIOLOGY. 125

have brought the bacteria within the reach of our
vision. A brief description of this part of bacterio-
logical work will therefore not be amiss, especially
since it has become of everyday utility.

In preparing for the microscopic examination
of bacteria the following steps are taken with
all fluid or semi-fluid specimens. A minute por-
tion of an artificial culture or of the microbe-
containing material is spread in a very thin layer
upon a slide or cover glass. This is allowed to
dry in the air, or is dried by gentle heating.
When dry, it is passed, prepared-side upward, three or
four times through the clean flame of a spirit lamp or
Bunsen burner. This coagulates uniformly the al-
bumen and cements the specimen to the glass, and it
is now ready for the important process of staining.
If the bacteria are to be inspected in their natural con-
dition, unstained, they are placed in a drop of distilled
water and immediately examined. Thus seen, the
germs are almost or quite colorless. It is therefore
customary to give to them an artificial coloring in
order to render them more visible and their outlines,
and to some extent their structure, more distinct.
For this purpose solutions of the basic anilin dyes are
generally used. Among these are two which have
been settled upon as answering all ordinary demands.
These are a red and a blue dye, named respectively
fuchsin and methyl blue. Solutions of these colors
are made in water or alcohol, or in both, and to these

126 ESSAYS ON BACTERIOLOGY.

solutions are sometimes added certain substances
which increase their power of staining. Most of the
known bacteria may be stained by exposure for a few
seconds or minutes to a simple watery solution of one
of these anilin dyes. The process may be hastened
or intensified or made applicable to otherwise resist-
ent organisms by heating the solution. If the bac-
teria still resist the dye, it may be made to “‘bite” into
them by the addition of mordants, such as anilin oil,
carbolic acid, or caustic potash, following the methods
used in the dyeing of cloth. The most vigorous
staining effects are secured by hot solutions contain-
ing such mordants, and thus only are certain bacteria
successfully colored. Spores are, as a rule, more re-
sistant to staining than the mature bacteria. A spe-
cial method of staining is that of Gram, in which
iodine dissolved in potassium iodide solution is used to
protect from decolorization certain bacteria which
have once been stained. The reaction of bacteria to
this method of staining having been determined, it
subsequently serves as an aid in identifying them.
Decolorizing agents, water, alcohol, and mineral acids,
are used when desirable, to remove an excess or all of
the dye from stained bacteria. All stained specimens
are washed in water before examining them. The
behavior of microbes under the influence of the
stronger decolorizing solutions is sometimes of much
significance in distinguishing them from others sim-
ilar in appearance. This is an essential feature of the

ESSAYS ON BACTERIOLOGY. 127

process by which the tubercle bacilli are recognized
for diagnostic purposes. Spores usually require the
application of the more energetic staining processes,
and resist the action of decolorizing agents more than
mature bacteria.. The staining of bacteria in thin
sections of tissue is accomplished by the method just
described, but requires nore time, more care in the
use of decolorizing agents, and often contrast colors
for the tissue. For the latter purpose we use one of
the acid anilin dyes, such as eosin, or a tissue stain like
carmine or hematoxylin. Double staining is the
process of giving one color to one variety of bacteria
and another contrast color to the others or to the sur-
rounding field. It is often of aid to the eye in locat-
ing and distinguishing a particular variety under the
microscope.

To illustrate these processes we prepare a number
of specimens upon thin cover glasses, spreading, dry-
ing and heating them so that all are ready for stain-
ing. We now test upon them the dyes prepared as
described above, a few drops of staining solution be-
" ing placed upon each glass. After a few minutes the
glasses are washed in water, the clean faces are wiped
dry, and they are ready for inspection. The first
specimens have been subjected to a cold watery solu-
tion of the dye. Examination shows most of the bac-
teria to have taken up the color. Several varieties re-
main colorless. A repetition of the process, except
that the glasses are held in forceps, prepared-side up-

128 ESSAYS ON BACTERIOLOGY.

ward, over a flame till the solution steams, reveals but
few varieties unstained. Again we stain a similar
series, using a cold solution containing 5 per cent. of
carbolic acid, repeating the procedure with the same
solution heated, and with solutions, cold and hot, con-
taining a minute quantity of potassium hydrate. In
the last specimens, stained with the mordants, we shall
probably find all the different varietis to have taken
up the dye.

If now we subject all of these specimens for a few
seconds to a 25 per cent. solution of nitric acid, the
color, as seen by the unaided eye, fades from all.
Microscopic examination shows that almost all of the
bacteria have been decolorized by the acid. One or
two varieties only retain the stain, standing out con-
spicuously colored upon a colorless background.
Upon close study these will probably be found to be
just the ones which resisted the simpler staining, re-
quiring the most energetic dyes. The tubercle bacil-
lus, for instance, stains with difficulty, but, once col-
ored, it resists the decolorizing agent to which most
others succumb. Selecting such a specimen, we stain
it again, after thorough washing to remove the acid,
with a watery solution of a contrast color. The re-
sistant bacteria do not take the dye, while other bac-
teria, mucus, and debris, making up the field, do.
The former present the one color, the latter the other.
And thus we see illustrated the selective action of the
dyes, and the staining and decolorizing reaction of

ESSAYS ON BACTERIOLOGY. 129

bacteria. In a score of ways these reactions may be
used in the staining and identification of disease
germs. It is fortunate that this is true, for thus only
is made easy and of everyday value the identification
of certain microbes the.recognition of which would
otherwise require the more difficult and tedious proc-
esses of culture and inoculation.

For the examination of bacterial specimens rather
‘high powers of the microscope, and therefore also
good illumination, are necessary. The latter is se-
cured chiefly by condensing lenses placed between the
mirror and the object. Immersion objectives have,
over dry objectives, the double advantage of increas-
ing illumination and diminishing the evils of refrac-
tion. Clearness and distinctness of the picture is as
important as magnification. That microscope is of
little value which shows “men as trees walking.”
Medium-power lenses may usually suffice for ordinary
purposes, provided their definition be good. But for
the highest class of work homogeneous immersion ob-
jectives, with strong and adjustable illuminating ap-
paratus, are necessary.

Inoculation experiments upon animals serve several
purposes. It is by this means that the truth of the
germ theory of disease has been finally and fully
proven. Inoculation experiments are the final steps
in deciding for or against the specific causative agency
of a particular germ. They afford, in otherwise
doubtful or difficult cases, most valuable diagnostic in-

9

130 ESSAYS ON BACTERIOLOGY.

formation. They settle the questions of duration and
degree of virulence in germs of varying activity.
They are the crucial tests of specific preventive and
curative methods and agents, such as the antitoxin and
antitoxie treatment of diphtheria. ‘Finally, they are
used to determine, with each infectious disease, the
various possible channels of infection.

Bacteria are inoculated on the skin, into and under
the skin, into the solid tissues and the body cavities.
They are introduced by feeding, by inhalation, and
even directly into the blood current. Thus, if the
supposed germs of erysipelas be under investigation,
they would be tested upon superficial wounds. Those
of cholera and typhoid fever would naturally be tried
by feeding; those of tuberculosis and suppuration by
all the methods. If we suspect that general miliary
tuberculosis is the result of an irruption of tubercular
material into a blood vessel, we may test the suspicion
by inoculations of tubercular cultures into the blood.
If we suspect the importance of a combination of non-
bacterial and bacterial factors in the production of a
disease, we may settle the question by experiments
with the former agents, then with the bacteria, and
then with both together. Such considerations reveal
the significance and value of inoculation experiments
in bacteriology, and their necessity in promoting its
beneficent work.

The history of bacteriology in its relation to prac-
tical medicine is similar to that of many other con-

ESSAYS ON BACTERIOLOGY. 131

tributions of science. Though. its importance and
value are now universally recognized, it is not many
‘years since it was looked upon with some suspicion
and even derision by many practitioners. Its place
was thought to be in the experimental laboratory
rather than in the consulting room. It was for the
student of science, not for the student of disease. The
same thing was said of the chemical and microscopic
examination of the urine. A physician of this city
has told the writer of hearing an eminent medical
teacher of the last generation say that he could learn
all that he wished to know about the urine by a study
of the case and an appeal to his unaided senses. To-
day the most unpretending doctor understands and
constantly practices examinations for albumen, sugar,
casts, and other abnormal urinary contents. There
are many physicians still living and working who re-
member the advent of the clinical thermometer and
the smile of incredulity with which it was generally
received. ‘The little instrument of thermometric ac-
curacy was a pretty scientific toy, but of no practical
value. Who could not detect the presence and judge
sufficiently of the degree of fever by the seuse of
touch alone? To-day every physician carries the in-
strument in his pocket and uses it in almost every case.
So it is proving of bacteriology. Those who, recog-
nizing or being taught early its meaning, began to use
it in everyday diagnosis, braving the harmless stigma.
of being theorists and unpractical, have now the pleas-.

132 ESSAYS ON BACTERIOLOGY.

ant satisfaction of recognition as pioneers not only of
science, but of everyday practical medicine. That
which often enables us to diagnose earlier, more ac-
enrately, and with more certainty than by any other
means, such common diseases as tuberculosis, malaria
and diphtheria, needs now no justification by him who
applies it. He knows, and it is now gladly acknowl-
edged, that he is exhibiting more than the interest and
zeal of the scientist: he is applying the helpful art of
the physician.

The number of diseases in which bacterial diagnosis
is applicable in everyday work is not yet large, but
fortunately it includes several of great practical im-
portance. The details of procedure are now so fully
set forth in the books on bacteriology, diagnosis and
practice that an extensive discussion of them here
would be out of place. A brief description of some
of them may, however, be appropriate.

Acute specific urethritis usually declares itself so
clearly in its symptoms and clinical history that bac-
terial diagnosis is seldom a necessity, though, being so
simple and rapid, it may properly be applied in every
suspected case. But in the presence of special cir-
cumstances or difficulties, clinical, medico-legal or so-
cial, it is of great value. The procedure is as follows:
Having prepared the specimen upon the cover glass
by the usual method of spreading, drying and heating,
it is floated upon or covered with a cold watery solu-
tion of methyl blue. After one-half minute to two

ESSAYS ON BACTERIOLOGY. 183

minutes, according to the strength of the solution, it is
washed thoroughly in water, the clean side wiped dry,
and it is ready to examine. Under the microscope
the diplococci of gonorrhea will be seen, in appear-
ance much like two coffee beans, lying upon or in the
pus cells. They will be stained deep blue, while the
nuclei of the pus and epithelial cells are light blue.
The bacteria occur singly or in swarms, usually within
“the cells, this being one of their striking character-
istics. The protoplasm of the cells may be counter-
stained with an acid anilin dye, an alcoholic solution
of eosin, thus making the picture more striking and
the bacteria more conspicuous; but this is of no great
importance. As thus carried out, the procedure is
sufficient for all ordinary clinical purposes. But
since there are other bacteria, more or less closely re-
sembling the gonococci, which may be found in the
same localities, examinations requiring medicolegal
accuracy must be carried further. The gonococci are
decolorized under the Gram method of staining.
They occur characteristically in groups within the
cells. They do not grow upon the ordinary culture
media, such as potato, beef gelatin, or beef-agar:
These tests having been applied the diagnosis be-
comes as nearly absolute as can be without culture
upon human blood serum and inoculations upon hu-
man beings.
The bacteriological diagnosis of diphtheria has a
special importance as a measure for the protection of

134 ESSAYS ON BACTERIOLOGY.

the public health and in view of the specific antitoxin
treatment. So true is this that in many cities, in-
cluding our own, laboratories and trained examiners
‘are provided, at’public expense, for doing this and
similar work. Many progressive practitioners also in
smaller communities are becoming skillful in thus
making the diagnosis. The microscope alone, while
often affording a high degree of probability to the ex-
pert diagnostician, is not thoroughly reliable, since
other bacilli, similar in appearance to those of diph-
theria, may be found in the throat, or the specific mi-
crobes may be few and escape detection. Cultiva-
tions are therefore necessary, and, fortunately, are not
difficult.

The bacilli of diphtheria stain fairly well with sim-
ple watery solutions of the basic anilin dyes. They
are most perfectly colored with the Leefiler alcoholic
solution of methyl blue containing a very small per
cent. of potassium hydrate. As thus stained, they
appear as straight or slightly curved rods, the ends
usually more strongly colored than the center, and
often staining in segments somewhat resembling a
chain of micrococci. A striking feature of these ba-
cilli is their variability of form, especially on different
culture media and in cultures or membranes of differ-
ent ages.

Diphtheria bacilli grow most rapidly upon Leefiler’s
culture medium, composed of three parts blood serum
and one part glucose-houillon. In the incubator the

ESSAYS ON BACTERIOLOGY. 185

growth precedes that of other bacteria which may be
present, often being recognizable in eight to twelve
hours. A particle of this growth, removed from the
tube and stained, reveals under the microscope the
characteristic picture of the diphtheria bacilli.
Scraping off with a sterilized wire or cotton swab a
small amount of the membrane from the throat or
other seat of disease, rubbing’ it onto the culture ma-
terial, and placing the latter in the incubator, the di-
agnosis can usually be settled in twleve or at most
twenty-four hours. Such cultures may also be made,
thotigh more slowly, by keeping the tubes in any
warm place, as near a stove or furnace register, and
upon any of the ordinary culture media. But for
rapid diagnosis blood serum is necessary. Should
questions arise as to the accuracy of such diagnosis or
the virulence of the microbes, they may be settled by
inoculations upon animals. The discovery of the spe-
cific diphtheria germ, and of methods of ready recog-
nition, has resulted in establishing the fact that what
has been called membranous croup is usually laryn-
geal diphtheria, and that there are many cases of. ex-
udative sore throat resembling diphtheria, some here-
tofore tentatively distinguished and some not, which
are due to other causes. It therefore affords a wel-
come means of eliminating hitherto unavoidable un-
certainty or error from reputable. practice, and impo-
sition from respectable charlatanism.

While the peculiar bodies found in the blood, and

136 ESSAYS ON BACTERIOLOGY.

commonly held to be the probable cause of malaria,
are not classified among the bacteria, yet their study is
so closely associated with bacteriology that reference
may properly be made to them here as in all recent
works on this subject. The malarial plasmodia are
protoplasmic bodies, varying in size and shape, often
pigmented, and to be found, most frequently during
or near the time of a paroxysm, in the blood of one
suffering from ague. They have not been success-
fully cultivated outside the body; final demonstration
of their character and specific causative agency is
therefore still lacking. Nevertheless they are so con-
stantly associated with the disease, and in such a sig-
nificant way, that their presence is now generally held
to afford ground for positive diagnosis, and therefore
for a clinical distinction between this and other dis-
eases. Bedside experience is constantly confirming
this belief. In obscure cases the examination of the
blood has come to be relied upon by the highest clin-
ical authorities. This examination, though at times
tedious, is not at all difficult. Puncture of the lobe
of the ear, or the finger, yields the droplet of blood,
which is transferred to the cover glass and immedi-
ately examined unstained. The blood specimen may
also be examined after staining with methyl blue, hav-
ing first been simply mixed with the dye or dried and
heated by the ordinary method; or, much better, fixed
by prolonged heating or by immersion in equal parts
of alcohol and ether. Counter-staining may be done

ESSAYS ON BACTERIOLOGY. 137

with alcoholic eosin. Following the latter method,
the blood cells are seen to be red, the bodies of the
parasites blue, their nuclei colorless, and the nucleolus
dark blue. Probably the most satisfactory plan is to
examine the blood unstained.

Different varieties of plasmodia have been described
as associated with the different types of malaria, but
this question, as well as many others concerning the sup-
posed malarial parasite, is still unsettled. Only the diag-
nostic value of the organism is generally agreed upon.

A number of diseases occurring only occasionally in
man, the microbes of which are known, may be posi-
tively identified by bacteriological methods. Such
are glanders, anthrax, and the ray-fungus disease,
actinomycosis. In a larger number of disorders, of _
which pneumonia, cholera, erysipelas and tetanus are ~
types, the identification of the bacteria is occasionally
of diagnostic value, though usually such procedures
are not called for. It is, however, possible, and with
increasing frequency and value, where a_ well-
equipped laboratory is available, to’ call bacteriology
into service in the diagnosis of infectious or suppos-
edly infectious diseases.

The character of several disorders, chiefly of the
skin, caused by microscopic fungi belonging to the
moulds or yeasts, may be established by the micro-
scope or by artificial cultivation of the parasites. To
this group belong ringworm, favus, and the brownish
scaly skin disease, tinea versicolor.

138 ESSAYS ON BACTERIOLOGY.

The bacteria generally believed to be the cause of
typhoid fever are so constantly associated in the ex-
cretions with others resembling them that they can-
not be identified by microscopic examination nor by
ordinary methods of cultivation. Bacteriology there-
fore does not, unfortunately, offer to the physician
any direct means of diagnosis in this disease. But of
late a procedure has come forward illustrating the in-
direct application of bacteriological diagnosis. Tt has
been observed that if typhoid bacilli are brought into
contact with the blood. serum of one suffering from
typhoid fever, they lose their motility and gather into
swarms. This Widal test is applied as follows: A
pure culture of typhoid bacilli being at hand, and
having been examined to make certain that the ba-
cilli show the normal motility, a particle of the cul-
ture is thoroughly mixed with distilled water, or, still
better, a fresh culture is made in bouillon, and from
this a few drops are taken. A drop of frésh blood or
of dried blood moistened with distilled water is now
added. From this mixture of typhoid bacilli and sus-
pected blood a portion is transferred to a cover glass,
the latter being immediately inverted over a concavity
in a glass slide. The microscope now soon shows the
bacilli gathering into swarms or clumps, and at the
same time losing their motility. Should both of
these phenomena occur, the reaction is said to be typ-
ical, and the inference is made that the blood came
from one suffering from typhoid fever. The time re-

ESSAYS ON BACTERIOLOGY. 139

quired varies from a few minutes to half an hour or
more, the bacteria-containing fluid being meantime
protected against drying by vaselin or other adhesive
applied to the margin of the cover glass.

The specific character of this Widal reaction is still
under debate. Should it prove to be such, it will be
of great clinical value in this disease, and may open
the way to a similar diagnosis of other diseases whose
bacteria are known but are difficult of identification by
ordinary means.

A method of diagnosis closely associated with,
though neither originating from nor entirely depend-
ent upon bacteriology, is that by inoculation. Inocu-
lation is frequently practiced as the final step in an
otherwise incomplete bacteriological demonstration,
but is sometimes sufficient of itself, and directly, to
establish a diagnosis. If in a suspicious case the dis-
covery or identification of the bacteria be difficult or
impossible, inoculation of animals with material from
the suspected body may result in such an unmistak-
able attack of the disease as to remove all doubt. Or
such inoculation, with its resulting disease in the ani-
mal, may afford an easy opportunity for the discovery
and identification of the bacteria. Thus glanders,
rabies and tetanus in animals or human beings may
usually be certainly identified by inoculation of sus-
ceptible animals. By this method obscure cases of
tuberculosis, in which the bacilli are not easily found,

, , such as those involving the skin, glands, bones, joints,

140 ESSAYS ON BACTERIOLOGY.

intestinal canal and genito-urinary organs, may be
cleared up.

It is probably in tuberculosis that bacteriological
diagnosis has won its most striking and complete tri-
umph. The frequency and seriousness of the disease,
and the importance of its early recognition, combine
to render this triumph the more noteworthy. It may
fairly be said that, by the skillful use of the means
now available, the diagnosis of tuberculosis, even in
its early and obscure forms, is almost completely com-
passed.

The microscopic identification of the tubercle ba-
cillus is made possible by its almost peculiar staining
reaction. It stains only with difficulty, but, being
stained, resists decolorizing agents more than other
bacteria. To this rule there are but few exceptions,
and those, with care, readily recognized in ordinary
work. Many methods, differing in details, and all
based upon the rule just stated, have been devised for
staining the tubercle bacilli. But few of them are in
common use. In the original Koch-Ehrlich method
anilin oil was used as a mordant. Carbolic acid has
been found to answer a similar purpose. The stain-
ing solution now generally used is called Ziehl’s car-
bol-fuchsin, being made as follows: To distilled wa-
ter is added 5 per cent. of crystallized carbolic acid, 10
per cent. of alcohol, and 1 per cent. of dry fuchsin.
After complete solution of the solids, and filtration, it
is ready for use. Decolorization is accomplished by

ESSAYS ON BACTERIOLOGY. 141

20 to 30 per cent. solutions of nitric acid. As con-
trast color, methyl blue is used in watery solution.
To hasten the process in everyday work the carbol-
fuchsin solution is applied hot, and to further save
time the decolorizing and counter-staining are accom-
plished in one operation by combining the methyl
blue and 25 per cent. sulphuric acid. In detail the
process is as follows: Having spread the suspicious
material upon cover glasses, dried and heated them,
by the method already described, the dye is dropped
upon the glass and the latter held by forceps over a
clean flame until steam rises. If evaporation occur
to dryness, more of the dye is added. A better
method, though more wasteful of staining solution, is
to heat the dye in a dish, floating the cover glasses
upon the liquid. After two or three minutes’ ex-
posure to the dye, the glasses are rinsed in water,
washed in the acid solution till the color fades out,
then in alcohol for a few seconds to wash out the al-
tered dye, and then thoroughly rinsed in water to re-
move the acid and aleohol. If examined at this stage
the tubercle bacilli will be seen stained red, other bac-
teria being colorless. To counter-stain the specimen
it is subjected for fifteen to thirty seconds to a watery
solution of methyl blue, after which it is again rinsed
in water. Inverted over a drop of distilled water and
examined, the tubercle bacilli will be found still red,
while other bacteria are blue. The whole process re-
quires from three to five minutes. By this method

142 ESSAYS ON BACTERIOLOGY.

the bacilli are somewhat altered in shape, and perhaps
do not resist strong decolorizing agents as well as those
colored by a slower process. The best results are got
by allowing the specimens to lie in the cold carbol-
fuchsin for twelve hours or more. If the bacilli are
few and therefore difficdlt to find, several methods are
available for concentrating them. Pure liquid car-
bolic acid added to sputum coagulates the parts most
likely to contain the bacilli, thus rendering the selec-
tion easier. If sputum be diluted with five or ten
times its volume of water containing a small per cent.
of potassium or sodium hydrate, and boiled, it be-
comes liquefied and may be set aside for a day or two
to settle in a conical glass. The sediment may now
be examined with more certainty of finding the bacilli.
Or the sputum, thus liquefied or simply shaken with
water, may be rapidly precipitated with the centrifu-
gal machine. The microscopic examination of the
specimen thus prepared may. at once reveal the tuber-
cle bacilli, or may require great care and painstaking,
involving considerable time and the study of a num-
ber of specimens obtained at different times. Only
positive results are of definite significance. The find-
ing of tubercle bacilli stamps the case as tuberculosis.
A negative result is only of relative significance, its
value depending upon circumstances and upon the
thoroughness and skill of the examination. It does
not absolutely exclude tuberculosis, since the bacilli
may not have been present in the material examined

ESSAYS ON BACTERIOLOGY. 148

or may have been overlooked. Sections of tissue to
be examined for tubercle bacilli are treated as follows:
They are stained for about thirty minutes in carbol-
fuchsin solution, washed for about one minute in 5
per cent. sulphuric acid, then for the same time in al-
cohol; they are then counter-stained for three or four
minutes in weak methyl blue, again quickly washed
in alcohol, immersed till clear in oil of cloves, and are
ready to examine in Canada balsam.

It is to be remembered that the successful identifi-
cation of the tubercle bacilli requires that the material
shall come from the seat of disease, shall contain the
bacteria, and that the examination shall have been
properly made. Failure of any of these requirements
will necessarily yield but negative results. Fortu-
nately, there remain two other available tests, the one
the inoculation of susceptible animals, already re-
ferred to, the other the diagnostic injection of tuber-
culin.

The tuberculin injection is, like the Widal test
for typhoid fever and the Mallein injection for the
detection of glanders, an illustration of indirect bac-
-teriological diagnosis. In 1890 Koch announced the
discovery, in the culture-products of tubercle bacilli,
of a substance which, being injected into animals or
men suffering from tuberculosis, would produce cer-
tain local and constitutional reactions and, as he then
thought, curative effects. Hopes thus raised in the
latter direction have not been fulfilled, for reasons

144 ESSAYS ON BACTERIOLOGY.

which Koch himself has recently admitted and ex-
plained. But the diagnostic significance of the tu-
berculin injection remains. Until recently this
method has, except in the hands of a few experiment-
ers, been restricted to the diagnosis of the disease in
animals. Here its value and reliability are now gen-
erally recognized by veterinarians. It is hardly too
much to say that to-day the efforts for the eradication
of tuberculosis among cattle and for the protection of
the public against tuberculous meat and milk center
about the tuberculin diagnosis. Of late the profes-
sion has been recovering from the fear of harm by this
procedure, and on good grounds. The dangers have
certainly been much exaggerated. The hypodermic
injection of from one-half to three milligrams of tu-
berculin will usually produce, in a person having any
form of tuberculosis, a recognizable reaction sufficient
to establish the diagnosis. The pulse quickens, the
temperature rises, and there is more or less accom-
panying local and general disturbance, all of which
subside within a few hours or days. In order that
the results may be correctly interpreted and possible
dangers avoided, certain precautions and preparations
are necessary. The tuberculin must be genuine and
not too old. It must have been proven free from con-
tamination, and should, if possible, have been pre-
viously’ tested upon a known case of tuberculosis.
The patient’s pulse and temperature should have been
recorded at regular intervals for several days, and a

ESSAYS ON BACTERIOLOGY. 145

careful physical examination should have been made.
Evidence of cerebral or renal tuberculosis should ex-
clude this method of diagnosis, and in all cases violent
reactions are unnecessary and should be avoided.
With these preeautions the tuberculin injection prom-
ises to become a valuable aid in the definite recogni-
tion of the disease in those early or obscure cases in
which the other means of diagnosis are not available.
The immediate future will doubtless bring the solu-
tion of some questions as yet unsettled concerning
this method. If it shall be settled that the tuberculin
reaction, properly induced, is a specific one, and lim-
ited to tuberculosis, and that the supposed dangers
may, by its skillful use, be practically eliminated, we
shall indeed be in a position to reaffirm the statement
heretofore ventured: that the diagnostic problem of
tuberculosis has been solved, and another contribution
made by bacteriology to practical medicine.

XI.

NON-BACTERIAL FACTORS IN INFEC-
TIOUS DISEASES.

HE writer has for some years past had much to
say upon the subject of bacteriology and the
germ theory of disease. He has also, largely by rea-
son of circumstances, often been called upon to act as
its special sponsor and defender. In so doing he has
always recognized, and as opportunity offered has em-
phasized, the danger of a one-sided view which would
overlook the other factors in the causation of the in-
fectious diseases.

This danger, however, does not chiefly threaten
those whose interest in bacteriology and opportunities
for its study have led to a somewhat thorough knowl-
edge, but rather the contrary. It might, I think,
_ fairly be said that those whose interest in and study of
bacteriology have led to something of a reputation as
‘bacteriologists, are, for example, not as much troubled
over the influence of a debauch in causing the drunk-
ard’s pneumonia as are many others over the question
of the role of bacteria in this disease.

The writer has, therefore, for some time had in
mind to prepare a paper upon the subject announced,

146

ESSAYS ON BACTERIOLOGY. 147

whose purpose should be, standing upon the double
ground of bacteriologist and clinician, to consider
somé of the non-bacterial factors in diseases caused by
bacteria. Such a paper may serve, and is intended to
serve, in some sense as a culmination of the series pre-
pared for the State Medical Society. By such a pa-
per, too, he hopes to aid in reconciling bacteriology
and clinical medicine by showing that a beautiful har-
mony exists between them. ;

There are two classes of physicians to whom an ad-
dress of this nature might be directed as a special plea:

First, there are some, ‘a diminishing company, who,
by reason of grossly defective knowledge and equally
gross misunderstanding of bacteriologists, have con-
ceived a pronounced and outspoken antagonism, even
amounting to scoffing, against the germ explanation
of disease. They love to hurl such epithets as bac-
teria-maniac, but they never dare to allow themselves
to be inoculated with cultures of anthrax or tubercle
bacilli. From such men emanate the furious anti-
microbic articles which occasionally appear in medical
publications, the best answer to which is the fact that
no well-informed man answers them at all.

Second, there are those who, being intelligent and
competent physicians, are yet perplexed with many
doubts in regard to the germ theory of disease because
they cannot reconcile it with the facts of clinical med-
icine. They recognize the meaning of the general
acceptance of the theory, and feel the force of its sim-

148 ESSAYS ON BACTERIOLOGY.

ple logic. They fall in with the advancing current of
opinion and conviction, and conscientiously obey its
impulses. But they cannot just tell why they are
where they are, or whither they and we are drifting.
Possibly some of us who have had much to say to
them about bacteriology have so frightened and con-
fused them that they are unable to see that, though
sometimes in the midst of foaming billows, they are
nevertheless floating on a clear and beautiful stream
of truth, and thercfore need have no fear of their
destiny. They will in time see that ancient land-
marks are only for the time being somewhat obscured,
somewhat changed, by the new view. To such I
hope to say a helpful word, by showing the fact and
method of a harmony between bacteriology and clin-
ical medicine.

And first a few words toward a mutual under-
standing:

I am to deal with the non-bacterial factors in the
infectious diseases; yet I shall have something to say
about such things as numbers and virulence of bac-
teria as influencing infection. By the words ‘“non-
bacterial factors” is therefore meant agencies other
than the mere presence of bacteria which influence
the development of the infectious diseases.

As to the degree to which such factors influence
particular infections, and the degree of importance to
be attached to them in clinical medicine, I have not

ESSAYS ON BACTERIOLOGY. 149

now much to say. The subject is of the greatest
moment, but is out of place here, since this is a study
of pathology, not of practice.

I shall assume two propositions to be true. First,
that the infectious diseases, have, as their prime and
essential cause, living poisons, commonly called germs,
bacteria, microbes, and that without them these dis-
eases do not exist. Second, that many agencies other
than the mere presence and growth of bacteria influ-
ence the development of the infectious diseases, even
to the extent of assuming the role at times of control-
ling factors. Can these two propositions be harmon-
ized? It is the chief purpose of this address to show
that they can, by showing that the non-bacterial fac-
tors influence the development of the infectious dis-
eases because they influence the growth of bacteria in
the body. And so the whole matter comes down to a
proposition which may be expressed in the simple
analogy from agriculture, thus: Crops of grain are
the products primarily and essentially of certain seeds;
all other factors influence the production of. grain
crops by contribution to the growth of those seeds.
So infectious diseases are primarily and essentially the
products of the growth of disease seeds or germs; all
other factors influence their development by contri-

g bution to the growth of these germs in the body. But,
, let me repeat, and be it remembered, this is the state-
ment for pathological, not necessarily for clinical

150 ESSAYS ON BACTERIOLOGY,

guidance. The agriculturist would not misinterpret
his part of the analogy; neither need the physician
misinterpret his.

We all recognize that there have been many fanci-
ful explanations of the infectious diseases, many
things fancifully invoked as factors in their causation.
But we all also recognize that even long before the
identification of disease germs various agencies, non-
bacterial in character, were shown to be closely asso-
ciated with and even to play a part in the production
of these maladies. The importance of these agencies
has been seen to vary in aifferent diseases and under
differing conditions, being sometimes but slight, some-
times seeming to stand in the foreground as exciting
or predisposing causes. But the fact of their impor-
tance and influence has been and is unquestioned and
unquestionable.

For example, no one asserts or believes that other
factors than the peculiar poison, except possibly age,
play an important role either as exciting or predis-
posing. causes of measles. But it is commonly and
strongly believed that the tubercle bacilli by no means
stand alone in the development of tuberculosis.
Every one recognizes, after the experience of recent
years, that the disease called la grippe, in its epidemic
form, attacks many without the aid of recognizable
predisposing causes. But every one also knows that
acute pneumonia seldom comes by infection alone.

Granting that the infectious diseases are, in the last

ESSAYS ON BACTERIOLOGY. 151

analysis, due to the growth of bacteria in the body,
the questions arise: What other agencies enter into
their production, and what role do such other factors
play? Can the facts of clinical experience and the
facts of laboratory work be harmonized?

I believe that in large measure they may. And,
further, if one will but observe closely, it will be
found that laboratory experiment in this direction has
confirmed many of the facts of clinical experience, has
furnished a more correct interpretation of others, and
has thrown light upon almost all. When we come to
study the factors other than the mere presence of bac-
teria which enter into infection, we find that they fall
into two groups, one relating to the persons infected,
the other to the bacteria. What now are some of
these factors, and to what extent has bacteriology in-
creased our knowledge of their importance and
meaning ?

First, race. It has long been observed that certain
races of men seem less susceptible to certain infections
than others. For instance, the negro is believed to
be less susceptible to yellow fever than the white.
Can we find confirmation of such a principle in the
bacteriological laboratory? We do find many. Thus
the rat is comparatively unsusceptible to anthrax,
while the guinea pig readily succumbs to small dosage.
Algerian sheep resist anthrax strongly, while ordinary
sheep easily fall a prey to this serious disease. Hens
and frogs have a natural immunity against anthrax,

152 ESSAYS ON BACTERIOLOGY.

and white mice against glanders. Dosage and other
conditions being the same, white rats yield to infec-
tion with anthrax most readily, gray rats next, and
black rats least. Many more examples might be
given illustrating the principle that the growth of dis-
ease germs may be more or less influenced by the race
or species of animal infected.

Second, just as race seems to play a part in the in-
fectious diseases, so does age. For instance, very
young infants seem to possess a relative insuscepti-
bility to measles and scarlatina; later their vulnera-
bility increases, and again seems to decline with ad-
vancing years.

The same thing may be demonstrated in the labor-
atory. It is a general rule, well known to bacterio-
logical experimenters, that young animals are more
readily infected with cultures of bacteria than are the
old. Certain animals, which at a mature age show a
strong degree of immunity against a disease, may be
comparatively easily inoculated in early life. In this
respect also, therefore, experiments with bacteria cou-
firm the observations at the bedside.

‘Third. Into the production of individual suscep-
tibility-many and various factors enter, some of which
we understand, while others are still mysteries. Some
are general, others local in action. Thus it has long
been observed that persons suffering from diabetes
mellitus are specially prone to the development of sup-
puration and tuberculosis; that erysipelas commonly

ESSAYS ON BACTERIOLOGY. 153

follows a wound, and that distinct traumatism is al-
most invariably the antecedent of non-tubercular sub-
cutaneous abscess. 2

Many experiments, some of them of a most ingeni-
‘ous character, have been made to solve the problems
of individual susceptibility, general and local. A few
of these may be cited:

The facts quoted in regard to diabetes being so con-
spicuous, suggested lines of experiment which have
proven most interesting and significant. Thus if
white mice are rendered artificially diabetic by feed-
ing with phioridzine, they at once become susceptible
to glanders bacilli, which, naturally, they strongly re-
sist. The ordinary pus microbes are, in small quan-
tities, ordinarily without much effect when introduced
under the skin of rats; but if associated with a solution
of sugar, suppuration is much more likely to occur.
Animals not susceptible to the disease called symp-
tomatic anthrax (black leg) may be successfully inoc-
ulated with these bacilli provided the animals are at
the same time injected with lactic acid.

Clinical experience indicates that many agencies
having a more or less general effect upon the body
predispose to infection, and there are definite bacterio-
logical experiments confirming the belief. Certain
animals fed on certain kinds of food are more suscep-
tible to anthrax than when otherwise nourished.
Starvation renders pigeons much more easily infected
with the same bacilli. Anthrax and some other bac-

154 ESSAYS ON BACTERIOLOGY.

teria have been shown to develop more certainly in
animals after great fatigue. Pus microbes, anthrax
bacilli, and other microbes, have been found to infect
with more certainty and violence certain animals in
which an artificial anemia has been produced by
bleeding. One of Pasteur’s classical experiments con-
sisted in rendering hens, ordinarily unsusceptible, sus-
ceptible to anthrax by artificial cooling of their
bodies; and conversely, artificial elevation of the tem-
perature of frogs has changed their natural immunity
into susceptibility to anthrax. A similar result has
been shown to follow in animals deprived of water.
Thus many of the things included under the general
term bad hygiene have been definitely shown to ren-
der animals more susceptible to the growth of bacteria.

Previous disease, as shown by clinical experience
and by definite bacteriological experiment, may pre-
dispose to subsequent infection, though this agency is
most often seen to act as a local rather than a general
predisposing factor.

Local, like general predisposition, may be brought
about by an indefinite number and variety of things
which temporarily or permanently injure the tissues.
Here belong traumatisms, local inflammations, ante-
cedent local or general diseases which produce distinct
local injury, and serious alterations in the local cireu-
lation of the blood.

The result of all such agencies is a locus minoris
resistentiae, a point of lessened resistance to the en-

ESSAYS ON BACTERIOLOGY. 155

trance and growth of bacteria. The broken skin not
only more readily admits bacteria, but the injured tis-
sue less easily resists their growth.

The poison of measles does not produce either
whooping cough or tuberculosis, but the respiratory
mucous membranes, altered and damaged by measles,
fall a more ready prey to the next invaders.

The inhalation of metallic or other dust cannot of
itself produce more than a simple inflammation with
resulting fibrosis. But it may open the way for the
entrance and growth of tubercle bacilli.

Some of the most beautiful of bacteriological ex-
periments have been made to test this matter of local
lessened resistance. It may be interesting to quote a’
few of these experiments.

Bacteria injected into the circulation do not often
attach themselves to the heart valves, neither does a
direct aseptic injury of the valves, as by a clean
needle, produce ulcerative endocarditis. In other
words, simple injury, or the mere presence of bacteria,
do not necessarily result in ulcerative endocarditis.
But let the valves be deliberately injured, and about
the same time let suppurative bacteria be introduced
into the blood current, and these bacteria will be
found lodged and growing at the point of lessened
resistance. A blow over the tibia without break of
the skin does not result in subcutaneous or subperios-
teal abscess. But experiment has repeatedly shown
that such simple injuries, which, if not infected, re-

Pose

156 ESSAYS ON BACTERIOLOGY.

main non-suppurative, are very likely to suppurate or
show other infection if the simultaneous presence of
bacteria be assured. Wandering bacteria are likely
to lodge at such a spot, just as vultures are to alight
upon carrion.

Other interesting experiments have been made
showing that the introduction of aseptic irritants to-
gether with bacteria into the tissues or directly into
the circulation is much more likely to be followed by
the lodgment and growth of the bacteria than when
the latter are introduced alone. And thus in all di-
rections the old doctrine of local and general suscep-
tibility to infection is confirmed and illuminated,
while at the same time the specific causative agency of
the bacteria remains unquestioned.

But not only do agencies affecting the body influ-
ence infection. Certain considerations concerning
the bacteria themselves are of great importance.
Here, too, clinical experience and laboratory experi-
ment agree.

Two children being exposed to apparently the same
degree to measles, one takes the disease while the
other does not. One child has virulent scarlatina or
diphtheria, while others in the same community have
but mild attacks. At one time a mild type of scarla-
tina prevails, as in this community during recent
years; at another we have to confront what a vener-
able practitioner among us has described as the dying
kind.

ESSAYS ON BACTERIOLOGY. 157

Let us see, now, leaving out of consideration ques-
tions of susceptibility affecting the body, how far bac-
teriology has thrown light upon these problems.

We expose, in an ordinary room, a series of culture
plates; after a time they are placed in an incubator,
and some are found to be infected with the microbes
of erysipelas, suppuration, tuberculosis, or diphtheria,
while others remain sterile or show only ordinary non-
pathogenic bacteria. The microbes have, in the terse
phrase of Welch, hit some and missed others. Imag-
ine now these plates to be living persons, and we at
once see one reason why, among a number seemingly
similarly exposed, some are attacked while others
escape.

Again examining our plates, we shall see another
significant fact: Some have developed but few col-
onies, while others show many. In a word, some have
been hit by many microbes, others by but few; hence
upon some a more pronounced growth than others.
Here, too, therefore, we see, in the number of bacteria
which fall upon the soil, a second possible explanation
of our problems. More direct experiment has abun-
dantly shown that the inference just suggested is cor-
rect. Let a series of similar lesions be infected with
bacteria taken from the same culture, but in varying
numbers, and, other things being equal, it will be
found that those lesions entertaining the larger num-
ber of microbes are more likely to be successfully in-
fected, and in a ratio of probability increasing with

158 ESSAYS ON BACTERIOLOGY.

the number of bacteria. This is more readily clinic-
ally recognized with those diseases, and experiment-
ally with those bacteria, susceptibility to which in the
animals experimented with is not great.

And thus we have established the bacteriological
doctrine that the number of bacteria in an important
way influences infection, confirming the clinical doc-
trine that quantity of poison and great exposure have
much to do in determining the development of an in-
fectious disease.

Examining our culture plates again, we may dis-
cover a third phenomenon: Upon some of these
plates the germs of diphtheria have fallen. We make
inoculation experiments and find that some of these
diphtheria bacilli are of great virulence, others pro-
duce but mild results, while others cannot be made to
produce either typical lesions or general symptoms of
diphtheria. Inoculating animals with these various
types of diphtheria bacilli, we find that some produce
pronounced local lesions with equally pronounced
constitutional symptoms. Evidently these germs pos-
sess their full biological characteristics. Others pro-
duce fairly typical local lesions, but little or no consti-
tutional disturbance, while others cause but slight
local disturbance. Yet these are all genuine diph-
theria bacilli. Evidently they differ biologically in
this, that some are possessed of their full powers, oth-
ers are weakened, while some have lost all or almosi
all pathogenic property. And this is the reason for
the different effects upon the inoculated animals.

ESSAYS ON BACTERIOLOGY. 159

And thus we’ become impressed with a third truth:
that the virulence of the microbes plays an important
role, not only in the typical development of an infec-
tious disease, but in the violence of the local and gen-
eral disturbance.

That personal immunity or susceptibility and vari-
ations in number and virulence of bacteria are often,
indeed usually, intricately combined is evident. So
true is this that the clinical evidence of the non-bac-
terial factors in infectious diseases is often difficult to
sift. We must turn to experiment upon animals for
a solution of many of the problems. The answer
which bacteriology has to give has, it is hoped, been
partly set forth. More might be said, but surely
enough has been brought out to show that clinical.
medicine and medern bacteriology are not and need
not be out of harzx my. And he who has a clear view
of both will be in no danger of being either a bacteria-
maniac or a bacteria-phobic.

A word in conclusion, and a simple illustration and
analogy. The more closely these things are studied
the more clear does it become that we have in bac-
teriology but another example of some very old
truths.

There is an ancient parable which tells us that a
sower went forth to sow, and as he sowed some seed
fell by the wayside, some upon ‘stony ground, and
some upon good soil, with’the result that some failed
entirely, some grew but faintly, while some flourished.

In the simple and stately scriptural phrase is set forth

160 ESSAYS ON BACTERIOLOGY.

the universally recognized truth of agriculture, that
other factors than the seeds have to do with the gath-
ering of a harvest.. The sun must. shine, the rain
must fall, and the soil must be suitable, or the harvest
will not come. Yet what agriculturist so simple-
minded as not to know that for a harvest of corn or
wheat he must plant the seeds of corn or wheat?

Does one imagine that catching cold causes pneu-
monia? Then let him also assert that sunshine pro-
duces wheat. Does he assert that bad water causes
typhoid fever? Then let him also assert that rain
causes oats. Does he believe that weak lungs degen-
erate and develop tuberculosis? Then let him also
assert that the soil of the earth produces corn.

Ts anyone perplexed when told that the germs of
diphtheria and pneumonia may sometimes be found
in the throats of healthy persons, and in the absence of
active disease? And does he therefore doubt the
specific causative agency of these bacteria or of all
bacteria? Let him, in the words of the poet, go out
to commune with nature. She will indeed speak to
him a varied language. Let him study the ground in
the winter, observing the various seeds scattered in
and upon the soil, yet producing no plants. Then let
him watch and see what occurs with the advent of
spring, with its sunshine and warmth. The seeds
sprout and grow, and the plant springs up; not be-
cause of the moisture and heat, but because these pre-
pared the way for the one thing essential, the seed.

ESSAYS ON BACTERIOLOGY. 161

Without the proper seed, the most fertile soil under
the most favorable conditions produces no corn, no
wheat. Without the specific germs the body suffers
from no typhoid, no diphtheria, no tuberculosis.

This simple, illuminating analogy between agricul-
ture and bacteriology I would leave as the last thought
with him who reads these pages. If he will bear it in
mind, he will seldom be at loss to understand the
germ theory of disease and many of the problems aris-
ing out of it. It will make him a better and a clearer
thinker about disease. And, being a clearer thinker,
he will be a more efficient actor as a physician.

When once he has seen, what every agriculturist
sees, that sunshine and rain and soil and seed must
work together to produce the harvest, then he will see
how germs may be the direct exciting cause of the in-
fectious diseases, into whose production, however,
many other factors enter, and often play an important
part. And then he will see the beautiful harmony
between clinical medicine and bacteriology, one truth
only aiding another.

RENN

AX

WY

A