ANNUAL ADDRESS. 
Modes of Infection. 
By william h. welch, m. d., 
Professor of Pathology, Johns Hopkins University, 
Baltimore. 
Reprint 
FROM TRANSACTIONS OF 
Medical and ffiftirnrgical yacttlft;, 
Of the State of Maryland. 
1887. [Reprint from “ Transactions of the Medical and Ghirurgical Faculty of 
Maryland ” for 1887.] * 
Annual Address. 
MODES OF INFECTION. 
By William H. Welch, M. D., 
Professor of Pathology, Johns Hopkins University, Baltimore. 
Mr. President and Gentlemen, Fellow-members of the Medico- Ohirur- 
gical Society: 
When honored by the invitation to deliver the Annual Address 
before this Society, it seemed to me appropriate to select a subject 
relating to that department of medicine in which the most important 
discoveries have been made in recent times. The far-reaching ad- 
vances in our knowledge of the causation of infectious diseases have 
opened up new fields of view in so many and in so various directions, 
that I have been somewhat in doubt as to what phase of the subject 
it would be most profitable for us to consider on the present occasion. 
The time has gone by when much profit is to be derived from the 
discussion of that very general and hackneyed theme, the germ 
theory of disease; for the doctrine thus expressed is no longer a 
theory, and there is, doubtless, no one competent to form an opinion 
on the subject who does not believe that certain infectious diseases 
are caused by micro-organisms, and that it is a logical inference that 
the other diseases of this class are produced by parasitic organisms— 
although there may be differences of opinion as to how far this 
doctrine has been proven for individual diseases. 
I have thought that it might be of interest to pass in review 
certain fundamental ideas concerning infectious diseases, and to 
note how far these ideas have been modified or expanded by recent 
discoveries. 
Many of these ideas are by no means of recent origin, for from 
the earliest times onward much attention has been devoted to the 
investigation of epidemic diseases, and particularly of their causa- 
tion. The conceptions of contagium and of miasm are almost as 2 
WILLIAM H. WELCH, M. D. 
old as the history of medicine itself. Ancient writers have recorded 
their belief in the existence of infected localities, and in the con- 
veyance of epidemic diseases by means of the drinking water and of 
the air. Individual predisposition to infection, as well as predis- 
position according to time and to place, are not modern ideas, as is 
shown by such historical terms as genius epidemicus, constitute pest- 
ilens. The science of epidemiology is much older than that of 
bacteriology, and has taught us much concerning the causation and 
development of infectious diseases. 
The question arises: Has our knowledge concerning the origin 
and spread of infectious diseases been widened and has it become 
more exact since the discovery of the living contagium of many of 
these diseases ? While granting the vast scientific importance of this 
discovery, it is in itself only the confirmation of the faith of far- 
seeing minds of past generations. The mere demonstration of that 
which was previously a reasonable supposition does not offer a new 
point of view. 
It is proper for us to inquire whether the investigation of the micro- 
organisms causing infectious diseases, and the study of the character- 
istics and life histories of these parasites, of the media and conditions 
of their growth and of the means of their destruction, have added 
materially to the knowledge which was already afforded us by the 
epidemiological study of these diseases. Have we thereby gained 
a clearer conception of such terms as miasm, contagium, and mias- 
matic contagium? Have we a deeper insight into the conditions 
under which a virus is transmitted from an infected to a healthy 
person, and of the conditions of infection through the air, the drink- 
ing water and other media ? Can we form any more definite ideas of 
what is meant by individual predisposition to an infectious disease 
and by such terms as predisposition in time and in place? 
Even if we were obliged to answer all of these questions in the 
negative, not one particle would be detracted from the importance of 
further pursuit of bacteriological studies, for experience has shown 
that nothing is more short-sighted than to estimate the value of 
scientific discoveries according to their immediate practical utility. 
And, moreover, the questions which I have raised relate to only a few 
out of many practical aspects of these studies; but if, as I believe to 
be true, it can be shown that light has been shed upon some of the 
most interesting and obscure problems concerning infectious diseases, 
by the studies of the living organisms causing these diseases, then it ANNUAL ADDRESS. 
3 
is apparent that the results of these studies are of more immediate 
interest and of interest to a much wider circle than would otherwise 
be the case. 
Our knowledge in the directions indicated is but fragmentary. 
The title “Modes of Infection” under which I wish to gather 
together some of these fragments has been selected as a convenient 
one to cover most of the thoughts which I desire to present to you. 
The intention, however, is not to consider exhaustively all possible 
modes of infection, but chiefly to dwell upon such points relating to 
the causation of infectious diseases as have been most illuminated by 
recent investigations, particularly in bacteriology. 
There is now tolerable unanimity of opinion as to tbe meaning 
attached to the terms infection and infectious diseases. Most recent 
authorities understand by infection the condition produced by the 
entrance and multiplication of pathogenic micro-organisms.within 
the body. An infectious disease is one which is caused by the 
invasion and reproduction within the body of pathogenic micro- 
organisms. To define an infectious agent as a specific poison capable 
of indefinite multiplication is only to express obscurely the idea just 
conveyed, for we know and can conceive of no poison capable of 
indefinite multiplication except a living organism. The analogies 
formerly drawn from the fermentation and the putrefaction of organic 
substances, and still preserved in the designation zymotic diseases, 
have lost all force as an opposing argument since it has been shown 
that these processes are produced by living organisms. In the 
absence of any other probable, I may say even conceivable, hypothesis, 
to refuse to accept the doctrine of a contagium vivurn as applicable 
to all infectious diseases because it has been demonstrated only 
for certain of these diseases, is about as reasonable as to reject the 
law omnis cellula e cellula because this has not been proven for 
every cell or every species of cell. 
We should be by no means justified to substitute in the foregoing 
definition of infection instead of pathogenic micro-organisms, bacteria 
or fissure-fungi. It is true that most of the infectious agents with 
which we have become acquainted are bacteria, but the malarial 
parasite is a notable exception to this. There are grounds for 
believing that the specific organisms of some of the infectious 
diseases may belong to low forms of animal or vegetable life other 
than the bacteria. Our means for demonstrating the presence of 
bacteria are comparatively satisfactory, but this cannot be said of most 4 
WILLIAM H. WELCH, M. D. 
of the other protozoa, and it is perhaps in consequence of this imper- 
fection of our methods of investigation that so many infectious 
diseases have resisted successfully our efforts to discover their 
efficient causes. 
It is gratifying, after so much strife, to be able to record this 
agreement of opinion as to the definition of infection and of infectious 
diseases in general. It is customary to classify infectious diseases 
etiologically into contagious, miasmatic, and miasmatic contagious 
diseases. As to the significance of these terms, and particularly as 
to the real nature of the so-called miasmatic contagious diseases, 
there exists great confusion. As the epithets miasmatic, contagious, 
and miasmatic contagious meet us upon every hand in our investiga- 
tions of infectious diseases, as they relate to conceptions which lie 
at the very foundation of our knowledge of the subject, it is mani- 
festly of the utmost importance that their meaning should, if possible, 
be rendered clear and precise. I question, however, whether these 
terms any longer suffice for the classification of infectious diseases, 
although, as Pettenkofer has said, the ideas contagium and miasm 
are so bred into our flesh and blood that we Avould as soon think of 
parting with them as with one of our limbs even after it had become 
useless. 
Originally the distinction between contaginm and miasm was 
sharply defined. There are two attributes which essentially charac- 
terize the ordinary conception of contagium, viz. multiplication 
within the diseased body, and capability of transmission from the 
diseased to the healthy body. The latter attribute implies, of course, 
the elimination of the contagious principle in an active state from the 
diseased body. On the other hand a miasm is produced outside of 
the body. According to the belief of many waiters it does not 
multiply within the body, and all agree that it is not eliminated 
from the body in a condition capable of producing infection. 
Especial emphasis in framing these distinctions was laid, in the case 
of a contagious disease, upon the origin of the virus within the body 
(endogenous), and in the case of a miasmatic disease, outside of the 
body (exogenous). These ideas concerning contagium and miasm 
answered well enough for the typically contagious diseases such as 
syphilis and the exanthematous fevers, and for the typically miasmatic 
disease, malaria. But confusion began during the middle third of 
the present century when the origin and spread of Asiatic cholera 
were carefully studied. It was found impossible to classify this ANNUAL ADDRESS. 
5 
disease under either of the two existing divisions. It has in common 
with the contagious diseases the characteristic that persons affected 
with cholera may convey the disease to localities previously free from 
it, and may prove the starting points of wide-spread epidemics. Cases 
sometimes occur of which the only natural interpretation is that they 
have originated from contagion. On the other hand, in infected 
localities the disease often develops in those who have never seen a 
patient, much less come into contact with one, while those in 
attendance upon such patients as a rule are no more liable to the 
disease than others living in the same locality. Similar observations 
were made with reference to typhoid fever. 
There arose the contest, not yet ended, between the contagionists 
who held that these diseases are to be ranked as contagious, and the 
localists who regarded them as miasmatic in origin, and to explain 
certain peculiarities introduced the new conception of a portable 
miasm. The majority, however, sought refuge under a new cover. 
The class of miasmatic contagious diseases was formed, and in this 
amalgamated group were placed cholera, typhoid fever, yellow fever, 
and several other infectious diseases not conveniently classified 
elsewhere. 
Various meanings have been and still are attached to the term 
miasmatic contagious diseases. Some understand by a miasmatic 
contagious disease one which is propagated sometimes by a conta- 
gium and sometimes by a miasm—that is, sometimes by a virus 
produced within the diseased body, and sometimes by a virus pro- 
duced outside of the body. Others hold the opinion that for the 
production of cholera, typhoid fever, and other diseases of this class, 
two viruses or micro-organisms are necessary, one derived from a 
person affected with the disease, and the other derived from the soil, or 
at least from some external source. But the view which has gained 
the most adherents, and which is the prevalent one at the present 
time, is that a patient with typhoid fever or with cholera throws olf 
from his body a poison, a micro-organism, which at the time of its 
discharge is not capable of producing the disease, but which under 
favorable circumstances undergoes outside of the body some unknown 
metamorphosis by which it acquires this power. This last view is 
the one which is accepted in most of the text-books on medicine 
published within recent years in this country and in Europe, and 
I presume that it embodies the belief on the subject of most practi- 
tioners of medicine. 6 
WILLIAM H . W E L C If , M. D. 
One of my main objects in the present address is to direct your 
attention to what seem to me weak points in this hypothesis, and to 
endeavor to explain in a more natural and satisfactory manner the 
peculiarities of the so-called miasmatic contagious diseases, at least so 
far as the two leading representatives of this group, viz. cholera and 
typhoid fever, are concerned. The discovery of the micro-organisms 
which are in all probability to be regarded as the specific causes of 
cholera and of typhoid fever, and the investigation of their 
should have led, it might be supposed, to a general revision of the 
widely accepted doctrine of miasmatic contagious diseases; but this 
has not been the case—at least among clinical writers, who apparently 
see no reason why the actually discovered germs, as well as those pre- 
viously surmised, may not undergo the assumed metamorphosis 
outside of the body which renders them capable of infection. This is 
still the reasoning of Liebermeister in his work on “Infectious Dis- 
eases,” published in 1885, in which he accepts the cholera and the 
typhoid bacilli as the agents of infection. 
Let us now examine in detail the arguments which are brought 
forward in support of the miasmatic contagious doctrine as previously 
defined. 
In the first place, it is urged that a metamorphosis such as is 
assumed to occur in the agents of infection after their elimination 
from the body of a cholera or a typhoid fever patient, has its analogy 
in the well-known instances of alternation of generation; and usually 
the ordinary tape-worm is cited, the ova of which, as is well known, 
first develop into cysticeri, and only these, when swallowed, are capable 
of giving rise to mature tape-worms. 
The argument by analogy, however, instead of supporting the 
miasmatic contagious hypothesis, is directly opposed to it. In the 
class of organisms to which the typhoid and the cholera germs be- 
long, no instance is known of any organism after its discharge from 
the body acquiring infectious properties which it did not previously 
possess, or of its undergoing any transformation at all resembling 
that assumed to occur. On the other hand, we know of some patho- 
genic organisms which are rendered more virulent by their passage 
through the body of an animal susceptible of the disease; and, in 
general, bacteriologists are inclined to regard as especially potent 
bacteria which are fresh from the bodies of infected animals. Where 
it is aimed to produce intoxication by means of ptomaines, as can be 
done by cultures of the typhoid and of the cholera bacilli, then it is A NNtr AL ADDRESS. 
true that old cultures, as would naturally he supposed, are the most 
effective; but there is no reason to believe that ptomaine intoxication 
plays any role in the primary infection with the typhoid or the cholera 
germs; or, if it did, where are the ptomaines likely to be more abun- 
dant than in fresh typhoid and cholera stools ? 
Before we knew as much as we now do about the properties of 
bacteria, the transformation hypothesis now under criticism could be 
advanced with some show of reason; but at present our information 
upon this and similar points is by no means scanty, and in the absence 
of any pertinent analogy for such an occurrence, the assumption 
seems entirely unwarrantable that the specific organisms of cholera 
or of typhoid fever acquire new or increased virulence after their 
removal from the body. Inoculation experiments upon animals with 
the cholera bacilli lend no support to this assumption. 
In the second place, it is urged in support of the miasmatic con- 
tagious theory that the specific germs of these diseases cannot be 
eliminated from the body in a condition capable of causing infec- 
tion; otherwise those who are in proximity to the patients must 
frequently become infected, as in cases of small-pox or of typhus fever. 
This is, evidently, the argument which has the greatest weight. It 
is to explain the absence, or at least the infrequency of any direct 
communication of cholera and of typhoid fever from one person to 
another, that the hypothesis under consideration was constructed. 
It is, of course, apparent that the specific germs of cholera and of 
typhoid fever must be discharged from the body in a very different 
way and must have very different properties from those of the con- 
tagium of small-pox and similar diseases. It is because our ideas of 
what characterizes a contagium are derived from our observations of 
such highly contagious diseases as small-pox or scarlet fever that we 
are loath to admit that cholera or typhoid fever patients emit any- 
thing which can be called an active contagium. I believe, also, that 
not a little of the difficulty of this admission comes from the popular 
notion that a source of active contagion must necessarily infect the 
surrounding atmosphere, as is the case with a small-pox patient. 
It is, however, possible to reconcile the fact that the discharges of 
cholera and of typhoid fever patients contain a contagium, and that, 
too, in an active form, with the infrequency with which these dis- 
eases are communicated in a manner which is ordinarily understood 
as contagious. 
Let us take for example cholera, and consider in the light of 8 
WILLIAM H. WELCH, M. D. 
recently ascertained facts what conditions must be fulfilled in order 
that the disease may be contracted directly from a patient. It is to 
be borne in mind that the cholera germ is discharged from the body 
only in the fgeces, and very exceptionally in the vomit. It is not 
present in the urine, nor in the breath, nor in the sputum, nor is it 
thrown off from the surface of the body. These are well established 
facts, so that we can conclude that the only danger of direct infec- 
tion from a cholera patient is by means of the stools. It is necessary, 
however, to come into actual contact with the stools in order to 
become thus infected. It has been proven by exact and very interest- 
ing experiments of Naegeli and Buchner that bacteria are never 
lifted by currents of air from the surface of fluids or from moist 
surfaces in general. One could remain in a room containing any 
quantity of cholera stools swarming with the cholera bacilli and 
there would be no danger of infection with cholera through the air. 
Bacteria are conveyed into the air only when they are in a dry con- 
dition, and the cholera organism is quickly destroyed by drying. So 
far as cholera is concerned, there is therefore no basis for the preva- 
lent belief that the atmosphere becomes infected for a certain dis- 
tance around substances containing an active contagium, although 
this belief is justified as regards certain other species of contagia. 
But it does not suffice for infection merely to have come into 
contact with the cholera stools; portions of the stools must actually 
be swallowed. There is every reason to believe that infection with 
cholera takes place only through the reception of the virus directly 
into the alimentary canal, and not through subcutaneous inoculation 
or through the respiratory organs. 
If this last condition be fulfilled and portions of cholera stools be 
actually swallowed, even then in any given case the chances are 
probably at leqst three to one that no infection would follow; for the 
cholera bacilli are destroyed by the acid of the gastric juice, and it 
is a matter of experience that only a minority of those exposed to 
the specific cause actually contract the disease. These considerations 
show how worthless are the isolated experiments of those foolhardy 
individuals who have voluntarily swallowed cholera dejecta and 
cultures of the cholera bacillus. Whatever had been the outcome 
of these few experiments, no positive conclusions could be drawn 
from them. A negative result, for reasons already given, was to be 
expected; a positive result would prove nothing, for the experiments 
were all made in districts already infected with cholera, and it would ANNUAL ADDRESS. 
9 
have been impossible to decide whether infection had taken place in 
a natural way or as the result of the experiment. The conditions 
were of course entirely different in the instance of the doctor in 
Koch’s laboratory who contracted cholera as a result of careless 
handling of cultures of the cholera bacilli, for there was at the time 
no cholera in Germany and no other possible source of infection than 
the cultures. 
Enough has been said to show what difficulties attend the direct 
communication of the disease by a cholera patient. It is perfectly 
explicable why direct contagion is so infrequent notwithstanding the 
fact that cholera stools contain the contagium in an active form, 
indeed sometimes almost as a pure culture. There is no necessity 
to resort to any such artificial, complicated and unsupported 
hypothesis as the miasmatic contagious doctrine in the sense at 
present under consideration. 
But any satisfactory explanation concerning the specific cause of 
cholera must account for occasional instances of transmission of the 
disease by contagion. I do not propose to discuss here in detail that 
most vexed question, Is cholera contagious ? but I believe that he 
who denies absolutely the contagiousness of the disease must shut his 
eyes to plain facts. There are instances, and of course they are to be 
sought not in regions where cholera is epidemic but where sporadic 
cases occur, where the only natural interpretation is in favor of direct 
contagion. 
Now the miasmatic contagious hypothesis has no room for these 
contagious cases, whereas there is no difficulty in accounting for 
occasional instances of contagion according to the view, which I 
believe to be an established fact, that the cholera stools contain 
the active cholera virus. Indeed, such instances of contagion are 
to be expected, although least frequently of course among doctors 
and nurses, whose comparative immunity is usually cited to prove 
the non-existence of any active contagium eliminated by a cholera 
patient. Doctors and nurses are the most likely to see that the cholera 
stools are properly disinfected, and also to disinfect their hands or 
other parts of their persons which may have become soiled by the 
dejecta. On the other hand, among ignorant persons living in 
cramped and unclean quarters the chances of direct contagion are 
much more favorable. It is probable that the statements in books 
relating to the frequency of cases of cholera caused by contagion 
are misleading, for such cases are least likely to come under the 10 
WILLIAM H. WELCH, M. D. 
observation of those who contribute most largely to medical literature, 
namely, physicians with practice in hospitals and among the well-to-do 
classes living under good hygienic surroundings. 
There is general agreement upon the point that the epidemic 
spread of cholera cannot be accounted for by direct contagion. It 
is generally admitted that the specific agent of infection, derived 
from the dejecta of a cholera patient, may under favorable conditions 
multiply outside of the body, in the ground, upon vegetables and 
elsewhere. We are to seek the chief sources of infection in cholera 
epidemics in the drinking water, the food, the ground, in actual 
contact with substances containing the specific germs. A discussion 
of these various external sources of infection, notwithstanding the 
great interest and importance of the subject, is not pertinent to 
my present argument, which is to show not only that it is not necessary 
to deny the existence of an active contagium in the fresh cholera 
stools, but that there is every reason to believe that such contagium 
is actually present. 
I have selected cholera for the purpose of showing the falseness of 
the miasmatic contagious theory as expounded by Liebermeister and 
others, partly because our knowledge concerning its etiology has 
become much more exact since Koch’s discovery of its specific germ, 
and partly because this disease has been generally regarded as the main 
support of this theory. Indeed, the hypothesis of the transformation 
or ripening of germs after they leave the body was constructed 
especially to account for the phenomena of Asiatic cholera. The 
arguments which I have presented apply equally to typhoid fever, 
another important member of the miasmatic contagious group of 
diseases. Here, too, the specific virus is eliminated from the body, as 
a rule, only in the feces. There exist the same reasons in the one as 
in the other disease why infection is likely to take place only 
exceptionally in the form of direct contagion. It is not necessary to 
go over the same ground with typhoid fever which we have already 
traversed with cholera, for as regards the points now under considera- 
tion the evidence is of the same character for both diseases. 
Our information is at present wholly insufficient to enable us to 
form any positive opinion as to the mode of elimination of the specific 
virus of yellow fever. 
I have attempted, gentlemen, to make it probable that a patient 
with cholera or with typhoid fever emits a contagium in just as 
active a state as a patient with small-pox or with scarlet fever. We ANNUAL ADDRESS. 
11 
cannot explain the difference in frequency with which the two sets 
of diseases are propagated by direct contagion by assuming that only 
in the latter diseases is the virus eliminated in a condition capable 
of producing infection. The relative frequency with which infectious 
diseases are communicated by direct contagion depends, I believe, 
first of all, upon the channels through wThich the virus is eliminated 
from the body. 
It may be stated as a broad proposition that every infectious dis- 
ease can by artificial means be transmitted from an individual affected 
with the disease to another individual susceptible of the disease. 
This is only the natural inference from the fact that each infectious 
disease has its specific virus in the shape of a micro-organism which 
is present and multiplies in the bodies of those affected with the 
disease. Although there is no evidence that under natural condi- 
tions malaria is ever transmitted from one person to another, still it 
is possible to accomplish this artificially, as has been proven by the 
experiments of such trustworthy observers as Gerhardt and Marchia- 
fava and Celli, who inoculated successfully, with blood from malarious 
patients, persons who were entirely free from malaria. 
Strictly speaking, therefore, in every infectious disease there is a 
contagium, but we should fall into grave errors if we drew our con- 
clusions as to the natural modes of infection from the results of 
artificial inoculations, as is illustrated by the example of malaria. 
To explain why, under natural conditions, some diseases, such as 
the exanthematous fevers, are usually transmitted by contagion; 
other diseases, such as typhoid fever and cholera, only infrequently, 
and other diseases, such as malaria, never by contagion, it is neces- 
sary, I repeat, to consider the channels by which the virus is elimin- 
ated, if at all, from the body. 
If, as in the case of malaria, the virus is not discharged at all from 
the body, then of course there is no possibility, under the conditions 
of nature, of the communication of the disease from one person to 
another. If, as in the case of cholera and of typhoid fever, the virus 
is discharged only by way of the faeces, then contagion is possible, but 
it is not likely to occur with ordinary care and with ordinary clean- 
liness. If, as in the case of scarlet fever, measles and small-pox, the 
virus is eliminated from the skin and adheres to thin scales of 
epidermis which can be readily transported through the air, then 
contagion is likely to be a common occurrence. 
I do not wish to he understood as implying that the mode of 12 
WILLIAM H. WELCH, M. D. 
elimination of a virus is the sole factor in determining the degree 
of contagion of a disease. There are, of course, other important 
factors, such as the degree of resistance offered by the virus to dry- 
ing, the chances of its being conveyed into the air, its quantity, etc., 
as well as the degree of susceptibility which exists on the part of 
those exposed and the portal through which the virus must enter in 
order to cause infection. 
I trust, gentlemen, that this will be found a more rational, fruitful 
and satisfactory way of regarding the infectious diseases than to 
wander among the mazes of miasmatic, contagious, and miasmatic 
contagious diseases, and to imagine that in some diseases the virus 
is eliminated in a potent state, and in other diseases in a state 
requiring some subsequent transformation to make it potent. 
It is unfortunate that our positive knowledge concerning the mode 
of elimination from the body of the specific poisons of the various 
infectious diseases is still very incomplete. Only for those diseases 
whose special agents of infection have been discovered is our infor- 
mation exact upon this point. For some other diseases we have good 
grounds for forming an opinion, while in the case of several infec- 
tious diseases, such as relapsing fever, we are quite in the dark on the 
subject. 
It may not be out of place to call your attention to certain points 
which bear upon this question. The experiments of Wyssokowitsch, 
made in the Hygienic Laboratory of Gottingen, and published not 
quite a year ago, have shown that non-pathogenic bacteria injected 
into the blood of animals in a few hours disappear from the blood 
and are deposited in certain organs, especially the liver, the spleen, 
and the marrow of the bones, whence they also disappear, as a rule, 
in a short time. They are not eliminated by the urine or by any 
other excretion. He found that micro-organisms in general are dis- 
charged by the urine only when they form some local lesion in the 
kidney or some part of the urinary tract. He found, likewise, that 
organisms injected into the blood are not discharged by the intestine 
unless they first cause some lesion of the alimentary canal. Similar 
facts were determined regarding secretions from other mucous mem- 
branes. The experiments of Wyssokowitsch warrant the following 
statements: 
The specific germs of infectious diseases can be and, in cases of 
recovery, doubtless often are, destroyed within the body. 
Contrary to what many have believed, the kidneys and the intes- ANNUAL ADDRESS. 
13 
tines cannot be regarded as important means of freeing the body 
from micro-organisms which have gained access to the blood. 
When the specific micro-organisms of an infectious disease are 
found in the urine or in the faeces, it may be inferred that the genito- 
urinary apparatus and the alimentary tract respectively are the seat 
of some lesion produced by these organisms. 
These experiments justify also the inference, in itself probable 
enough, that the specific viruses of infectious diseases are discharged 
from those free surfaces which are themselves the seats of the charac- 
teristic lesions of the disease, as for instance from the respiratory 
tract in pulmonary tuberculosis, lobar pneumonia, whooping cough, 
diphtheria; from the skin, in scarlet fever, measles, small-pox, 
typhus fever, erysipelas; from the intestines, in typhoid fever, cholera; 
from the urethra or vagina in gonorrhcea, syphilis. For several 
diseases, however, we have no satisfactory data for determining in 
what manner the special poison is eliminated. This is true, for 
instance, of cerebro-spinal fever and relapsing fever.4 
We are ignorant as to whether micro-organisms may be eliminated 
by the breath, although it is a common notion that this occurs. In 
view of the experiments already cited, which show the difficulty with 
which micro-organisms are detached from moist surfaces by currents 
of air, it seems improbable that organisms can be conveyed from the 
body by the breath. Of course, if the organisms were momentarily 
set free by acts of coughing, then they might be carried on by the 
respiratory current, but it is at least very questionable whether in 
ordinary breathing particulate substances can be thus transmitted. 
We have up to this point, gentlemen, considered only the diseased 
body and its fresh excreta as the source of infection, and we have 
reached the conclusion that in every infectious disease there is a 
contagium, but that whether or not the disease is likely to be propa- 
gated as a contagious one depends upon various circumstances, among 
which the mode of elimination of the contagium from the body is of 
the utmost importance. 
A question of great interest, as well as of practical importance, is 
whether or not any given infectious agent finds conditions outside of 
the body favorable for its prolonged existence. This question is not 
identical with that of the reproduction of the special virus outside 
of the body. The importance of the latter point has been somewhat 
exaggerated in discussions relating to the etiology of infectious 
diseases. Special agents of infection may be widely distributed 14 
WILLIAM H. WELCH, M. D. 
without their finding conditions favorable to reproduction outside of 
the animal body. Thus the bacillus of tuberculosis appears to be 
almost as widely spread throughout nature as the organisms which 
cause suppuration, and yet the tubercle bacillus can find only 
exceptionally the conditions of temperature and of nutriment which 
permit its multiplication outside of the body, whereas the pus organ- 
isms doubtless find abundant opportunities for their development on 
various substances outside of the body. 
The mere facts of the wide distribution of certain infectious 
micro-organisms and of frequent infection from external sources do 
not justify us in drawing conclusions as to the capability of growth 
of the organisms as saprophytes. This is a point which can be 
positively decided only by a knowledge of the life history and 
properties of the different infectious organisms. 
So far as our present knowledge reaches, it is only such infectious 
micro-organisms as form spores which are capable, under natural 
conditions, of p*olonged existence outside of the body without repro- 
duction. These spores can resist high temperatures, drying, and 
various other agencies which are destructive to the ordinary vegetative 
cells. Thus we can explain why, for instance, infection Avith the 
tubercle bacillus can take place from external sources, while infection 
with gonorrhoea always requires contact with fresh gonorrhoeal secre- 
tion, although in neither instance does the special virus reproduce itself 
outside of the animal body, except under such artificial conditions as 
we can produce in our laboratories. 
The question as to the reproduction of infectious micro-organisms 
outside of the body, although it has not all of the significance some- 
times attached to it, is nevertheless one of much interest. It is from 
this point of view that infectious micro-organisms are often classified 
by bacteriologists. Thus there are micro-organisms which find only 
within the animal body the conditions suitable for their growth 
and development. Such organisms are called obligatory parasites. 
Examples are the parasitic organisms of syphilis, gonorrhoea, tuber- 
culosis, and doubtless of small-pox, measles, scarlet fever, etc. Other 
infectious micro-organisms are capable of growing under natural 
conditions both within the body and outside of the body, as in the 
soil. Such infectious agents are called by bacteriologists potential 
parasites. In the case of some of the potential parasites their natural 
home seems to be the animal body, as appears to be true, at least in 
most localities, of cholera and typhoid fever bacilli; -while in other ANNUAL ADDRESS. 
15 
cases the natural habitat of the organism is the soil, whence it makes 
occasional excursions into the animal body. The malarial parasite 
conforms to the latter type. The growth of micro-organisms outside 
of the body is spoken of as saprophytic. 
In the case of typhoid fever there is no a prion objection to sup- 
posing that its parasite may grow in situations where it has not been 
introduced by any human being. The weight of evidence seems 
certainly opposed to such a supposition; still Murchison and other 
authorities have contended for the so-called spontaneous origin of 
typhoid fever in some cases, and the question can be settled only by 
a careful analysis of epidemiological facts, in the interpretation of 
which there inhere, as is well known, important sources of error. 
Of the utmost importance in the elucidation of the spread of many 
of the infectious diseases, particularly of cholera and of typhoid 
fever, is the investigation of the conditions favorable to the exist- 
ence and growth of parasitic micro-organisms in the soil, the drink- 
ing water, upon vegetables and other substances outside of the body, 
as well as of the means by which infection occurs from these external 
sources. These subjects, which pertain to public hygiene, can be 
touched upon only very briefly upon this occasion. 
More attention has been paid to the influence of the soil and of 
the drinking water in the propagation of epidemic diseases than to 
any other of the factors named. Under the brilliant leadership of 
Pettenkofer a school of hygienists has developed who lay emphasis 
almost exclusively upon the soil in this matter, and are unwilling 
to admit that epidemic infection takes place through the drinking 
water. 
We owe to this school valuable researches as to the physical con- 
ditions of the soil which favor the development into an epidemic of 
such diseases as cholera and typhoid fever, as well as to conditions 
hostile to such development. Among the conditions favorable to an 
epidemic may be mentioned a certain degree of porosity of the soil, 
a certain amount of moisture, and some impregnation with decom- 
posing animal and vegetable material. But notwithstanding these 
painstaking investigations, which are much more extensive than this 
brief notice would indicate, it must be admitted that they have left 
us considerably in the dark as to how we are to regard the soil as 
concerned in the propagation of infectious diseases. There has been 
no actual demonstration of the infectious micro-organisms of cholera 
and of typhoid fever in the soil, or of their multiplication there, 16 
WILLIAM H . WELCH, M. D. 
and, above all, no satisfactory explanation as to the means by which 
infectious agents are transported from the soil to the animal body. 
To the medical profession in this country and in England it is not 
comprehensible how there can still be distinguished authorities who 
deny that epidemics of typhoid fever or of cholera are ever attribu- 
table to the drinking water. Yet in Germany there are hygienists 
who are not only quite positively, but even somewhat violently 
opposed to what they call the drinking water hypothesis. It is doubt- 
less true that we are often too ready to accuse the drinking water 
in an outbreak of typhoid fever; but if medical evidence is worth 
anything, there can be no reasonable doubt that many epidemics of 
typhoid fever have been due to contamination of the drinking water 
with the typhoid virus. 
The experiments of Meade Bolton have revealed the important fact 
that most pathogenic micro-organisms do not multiply in water 
sufficiently pure ever to be used for drinking purposes. Not only 
do the pathogenic bacteria not multiply in drinking water, but, if 
they do not contain spores, most of them are destroyed in drinking 
water in a short time, varying from a few hours to several days, 
according to the species and the quantity of bacteria. These experi- 
ments have been hailed by the Munich school of hygienists as opposed 
to the view that epidemic infection can take place through the drink- 
ing water, but they need not be so interpreted, nor are they so inter- 
preted by Bolton. 
These experiments make it necessary to suppose that a single 
infection of the drinking water with infectious organisms would not 
suffice for an epidemic lasting more than a few days. To keep up a 
long-continued epidemic by means of contaminated drinking water, 
there must be some communication between the water and some focus 
in which the disease-producing organisms are present in large 
number or are multiplying. This is in harmony with the fact that 
repeatedly in epidemics traceable to the water, communications have 
been proven to exist between the water and cess-pools, drains, privies, 
or other possible foci of infection. In considering water as a source 
of infection, one must remember that this can occur not only by 
drinking, but also by the use of the water in cooking, and in washing 
dishes subsequently used to contain food. 
As is well known, there have been several epidemics of typhoid 
fever in which the source of infection has been traced to the milk. 
Although in these instances it was believed that the milk was itself ANNUAL ADDRESS. 
17 
infected by the addition of contaminated water, nevertheless it is 
well to note that in one important particular milk differs from water 
in its behavior toward pathogenic micro-organisms. Milk is an 
excellent nutritive medium for nearly all of these organisms. The 
typhoid and the cholera bacilli grow in milk rapidly and abundantly, 
without producing any alteration in the external appearance of the 
milk. Inasmuch as certainty of infection depends, in the case of 
many diseases, upon the number of organisms which enter the body, 
it is apparent that this property imparts a particularly dangerous 
character to infected milk. 
As regards the. means of transportation by which the agents of 
infection are conveyed from external objects to the body, the most 
important is believed to be the air by those who lay the most stress 
upon the influence of the soil in the spread of epidemic diseases. 
It seems probable, however, that too big a role has hitherto been 
assigned to the air as a carrier of contagion. The fact has already 
been mentioned that currents of air are incapable of lifting bacteria 
from moist surfaces; and Naegeli has shown, also, that if bacteria be 
dried with their natural gelatinous envelopes or from albuminous 
substances, they are in much the same physical condition as insects 
attached to a surface by mucilage, and cannot be carried away by the 
air unless they are first converted into a dust-like powder. If it be 
furthermore considered that some bacteria are destroyed by complete 
desiccation, it is evident that these facts compel us to restrict within 
much narrower limits than most writers have done, the importance 
of the air in the transportation of agents of infection. Still there 
remains evidence enough that the virus of some diseases, notably of 
malaria, and probably of yellow fever, may be, and often is, con- 
veyed through the atmosphere. As infection through the air is 
something which we have no means of combating, it is encouraging 
to learn that this resistless fate has a narrower sway than we had 
been led to believe. 
There are many grounds for supposing that the chief means of 
infection are by actual contact, in one way or another, with the agents 
of infection. The conviction of the truth of this statement is borne 
in almost irresistibly upon one who has engaged extensively in the 
cultivation of micro-organisms. I have kept for weeks at a time, 
side by side in a sterilized dish to which filtered air had free access, 
two watch-glasses, one containing a culture of the typhoid bacilli in 
beef tea, the other containing simply sterilized beef tea. During 18 
WILLIAM H. WELCH, M. D. 
this time, notwithstanding its close proximity to the typhoid culture, 
the beef tea in the second glass remained perfectly pure, without a 
trace of contamination from its neighbor. Many illustrations of the 
same principle might be drawn from the work of a bacteriological 
laboratory. We study the exposed cultures of such pathogenic 
organisms as the anthrax bacilli, the cholera bacilli, the glanders 
bacilli, and run no risk of infection from these so long as we do not 
come into contact with the cultures. 
There is one observation which we sometimes make in our labora- 
tories in summer—to our discomfiture—which, although it may 
seem trivial, is not without its practical bearings. This is the readi- 
ness with which micro-organisms may be disseminated by flies and 
other insects. Upon the so-called plate cultures we can sometimes 
trace the devious wanderings of an insect by the colonies of micro- 
organisms which it has planted in its course. The application of 
this experience to a possible means of transportation of the special 
organisms of infectious disease is too apparent to need further eluci- 
dation. 
I shall not weary you by attempting to elaborate in all of its 
details the doctrine that one of the chief means of infection is by 
contact. There are thousands of ways in which we can inadvertently 
come into contact with sources of infection. This teaches us that 
it is an error to construct exclusive theories of infection, such as 
are expressed by the terms “ soil hypothesis,” “ drinking water hy- 
pothesis,” etc. 
There is one lesson, however, which has come from the epidemi- 
ological study of the relations of the soil and of the drinking water 
to infections diseases, and that is the immense importance of the 
proper disposal of the refuse matter around human habitations and 
the supply of pure drinking water. The efficacy of a good system 
of drainage or of sewerage in preventing the development of many 
epidemic diseases is probably to be sought, not in the purifying of 
the ground so that pathogenic organisms cannot grow there, but in 
affording means by which these organisms, contained in human 
excreta and other substances, are readily carried away. The discussion 
of these points relates to sanitary science, and does not belong to my 
theme, but I cannot refrain from a brief allusion to the subject on 
account of its great practical importance. 
What can be more instructive, as well as more encouraging, than 
to witness the manner in which Asiatic cholera, during its present ANNUAL ADDRESS. 
19 
journey, has failed to secure any foothold in those European cities 
which are characterized by cleanliness and proper sanitary arrange- 
ments, although it has been repeatedly introduced into such cities ? 
These cities have secured their immunity, not by spasmodic pre- 
cautionary efforts after the entrance of the disease, but at the price 
of systematic, vigilant, and intelligent exertions during what may be 
termed the time of peace. Without wishing to pose as an alarmist, 
I believe that with the announcement of the appearance of Asiatic 
cholera upon this continent, the time has come to emphasize the 
fact that the only enlightened and civilized public policy is to be 
prepared at all times and in all places to meet the enemy. 
Of the various factors entering into the causation of infectious 
diseases none is more obscure than that designated predisposition, 
and yet this is a factor with which we must undoubtedly reckon. 
This mysterious predisposition to certain infectious diseases plays, 
perhaps, even a greater role with us, at the present time, than it did 
with our forefathers in medicine, who wrote so much concerning con- 
st itutio epiclemica. 
It cannot be said that the increase in our knowledge concerning 
the specific causes of infectious diseases has illuminated to any great 
extent what is meant by predisposition, and still a few glimmers of 
light,have been sent into this dark corner by recent bacteriological 
investigations. 
Mention has already been made of the fact that the cholera bacilli 
are destroyed by the acid gastric juice, so that we are warranted in 
regarding all conditions which neutralize the acidity of the gastric 
juice as affording predisposition to this disease. 
Perhaps the most positive addition to our knowledge in this 
direction has been the demonstration of the importance of pre-exist- 
ing diseases or lesions of structure in affording ready means of ingress 
and suitable conditions for the lodgment and growth of pathogenic 
micro-organisms within the body. In this connection attention may 
be called to the experiments of Wyssokowitsch and of Prudden, 
which show the necessity of previous alterations of structure in the 
cardiac valves before they are adapted for the lodgment and develop- 
ment of the micro-organisms which cause ulcerative endocarditis. 
Grawitz has shown that the bacteria of suppuration may be injected 
in large quantity into the healthy peritoneal cavity without doing 
any damage, but that they set up suppurative peritonitis if they 
meet there wounded tissues, stagnating fluids, or so-called dead spaces 
from which they are not readily absorbed. 20 
WILLIAM H . WELCH, M. D. 
Especially instructive in this light is the study of the manifold 
complications which attend scarlet fever, typhoid fever, and other 
diseases which are accompanied by necroses and ulcerations of the 
mucous membranes of the throat, intestine, and other parts with 
which micro-organisms are normally in contact. While it has been 
shown that most of these micro-organisms are harmless, there are 
not infrequently among them some which are pathogenic, such as 
the cosmopolitan bacteria of suppuration. The superficial necroses 
and ulcerations of the mucous membranes in scarlet fever and typhoid 
fever afford means of ingress for these bacteria, which often find 
within the body foci of least resistance resulting from the existing 
diseases. We are therefore not surprised to learn that many of the 
complications of these diseases are produced by the staphylococci and 
streptococci of suppuration, or that there are frequently found in 
these diseases in the tissues and fluids bacteria, particularly micrococci, 
which have nothing to do with the specific cause of the primary 
disease, although often enough mistaken for it by hasty observers. 
Time will not permit me to elaborate the ideas here touched upon. 
Enough has been said to show that we need not despair of gaining 
some definite conception as to the nature of predisposition and 
immunity to disease, but we must not forget that our positive 
knowledge at present touches only the outlying boundaries of the 
subject. We do not even know why different species of animals 
behave differently toward infectious agents—why, for instance, house 
mice resist the deadly glanders bacilli, while the more hardy field 
mice readily succumb—still less can we account for differences in 
susceptibility of individuals of the same species. 
It is easy enough to construct plausible theories of predisposition 
and of immunity, and such theories have their scientific uses ; but we 
must remember that we have gained no explanation of the facts 
when we base our theories upon such popular phrases as struggle for 
existence between cells and bacteria, or fitness of the soil for the 
growth of bacteria, etc. Even the more tangible phagocytic doctrine 
of Metschnikoff cannot be said to have materially advanced our 
knowledge as yet, or to have met with much support in facts. 
Before leaving this subject it may be well to say that possibly we 
are at present in the habit of assigning too great importance to 
predisposition as a factor in the causation of infectious diseases. It 
is such a convenient refuge that we are tempted to bury in its 
obscurity many etiological facts which we cannot readily explain. ANNUAL ADDRESS. 
21 
While I would not by any means ignore the importance of heredit- 
ary predisposition to tuberculosis, is it not probable that cases are 
often included in this category which do not belong there? When 
we think of the especial dangers of infection to which -the offspring 
of tuberculous parents are exposed from their youth upward, of the 
likelihood that a child will follow an occupation which has favored 
the development of phthisis in a parent, and of the frequency with 
which the concurrence of the disease in ancestor and descendant is 
mere coincidence, it is apparent that we are in danger of assigning 
to heredity a larger part in the causation of tuberculosis than it 
deserves. 
It must be admitted that the instances in which we have been 
able by experiments upon animals of the same species to demonstrate 
different degrees of predisposition toward infectious agents are not 
very striking or very numerous. 
And now, gentlemen, I bring to conclusion this imperfect survey 
of some points relating to the etiology of infectious diseases. We are 
only upon the threshold of a deeper insight into the nature of a 
class of diseases which have been more devastating to the human 
race than any upheavals of nature or any wars. They have left 
their imprint upon the political, the social and the intellectual 
history of the world. One need not be of a very sanguine tempera- 
ment to hope that our steadily increasing knowledge will bear fruit, 
not only, as in the past, in the prevention of these diseases, but also 
in a rational system of causal therapeutics.