Adaptation in Pathological Processes. 
WILLIAM H. WELCH, M.D., 
BY 
t PROFESSOR OF PATHOLOGY, JOHNS HOPKINS UNIVERSITY. 
FROM 
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 
June, 1897. Extracted from The American Journal of the Medical Sciences, June, 1897. 
ADAPTATION IN PATHOLOGICAL PROCESSES.1 
By William H. Welch, M.D., 
PROFESSOR OF PATHOLOGY, JOHNS HOPKINS UNIVERSITY. 
Grateful as I am for the personal good-will manifested by my selec- 
tion as President of this Congress, I interpret this great and unexpected 
honor as an expression of your desire to give conspicuous recognition to 
those branches of medical science not directly concerned with profes- 
sional practice, and as such I acknowledge it with sincere thanks. 
All departments represented in this Congress are working together 
toward the solution of those great problems—the causes and the nature, 
the prevention and the cure, of disease—which have always been and 
must continue to be the ultimate objects of investigation in medicine. 
It is this unity of purpose which gives to the history of medicine, from 
its oldest records to the present time, a continuity of interest and of 
development not possessed in equal degree by any other department of 
knowledge. It is this same unity of purpose which joins together into 
a single, effective organism the component groups of this Congress, rep- 
resenting, as they do, that principle of specialization and subdivision of 
labor which, notwithstanding its perils, has been the great factor in 
medical progress in modern times. 
Medical science is advanced not only by those who labor at the bed- 
side, but also by those who in the laboratory devote themselves to the 
study of the structure and functions of the body in health and disease. 
It is one of the most gratifying results of the rapid advance in medical 
education in this country during the last few years that successful 
workers in the laboratory may now expect some of those substantial 
rewards which formerly were to be looked for almost exclusively in the 
fields of practical medicine and surgery. We already have abundant 
assurance that the steady improvement in opportunities and recompense 
and other material conditions essential for the prosecution of scientific 
work in medicine will enable this country to contribute to the progress 
of the medical sciences a share commensurate with its great resources 
and development in civilization. 
The subject of “Adaptation in Pathological Processes,” which I 
have selected for my address on this occasion, is one which possesses the 
1 Address of the President before the Fourth Congress of American Physicians and Sur- 
geons, held in Washington, May 4-6,1897. • r V; 2 
WELCH: ADAPTATION IN PATHOLOGY. 
broadest biological, as well as medical, interests. It is this breadth of 
scientific and practical interest that must justify my choice of a 
theme which involves many technical considerations and many prob- 
lems among the most obscure and unsettled in the whole range of biology 
and of medicine. 
I shall employ the epithet “ adaptive” to describe morbid processes 
which bring about some sort of adjustment to changed conditions due 
to injury or disease. In view of the more technical and restricted mean- 
ing sometimes attached to the term “ adaptation” in biology, objection 
may be made to this broad and general application of the word in pathol- 
ogy ; but no more suitable and convenient epithet than “ adaptive ” has 
occurred to me to designate the entire group of pathological processes 
whose results tend to the restoration or compensation of damaged struc- 
ture or function, or to the direct destruction or neutralization of injurious 
agents. Processes which may be described variously as compensatory, 
regenerative, self-regulatory, protective, healing, are thus included under 
adaptive pathological processes. These processes are, in general, more 
or less advantageous or useful to the individual; but for reasons which 
will be stated later the conception of pathological adaptation and that 
of advantage to the individual are not wholly coextensive. 
Within the limits of an address I cannot hope to do more than direct 
attention to some of those aspects of the subject which seem to me to be 
of special significance. Although most striking examples of adaptation 
are to be sought in comparative and vegetable pathology, what I shall 
have to say will relate mostly to human pathology. My purpose is not 
to point out the beauties or the extent of adaptations in pathological 
processes, but rather to say something concerning the general mechanism 
of their production and the proper attitude of mind regarding them, 
and to illustrate the general principles involved by a few representative 
examples. 
It has been contended that the conception of adaptation has no place 
in scientific inquiry ; that we are justified in asking only by what means 
a natural phenomenon is brought about, and not what is its meaning or 
purpose; in other words, that the only question open to scientific inves- 
tigation is How ? and never Why ? I hope to make clear by what fol- 
lows in what light I regard this question, and in this connection I shall 
simply quote Lotze, who, beginning as a pathologist, became a great 
philosopher : “ Every natural phenomenon may be investigated not only 
with reference to the mathematical grounds of its possibility and the 
causes of its occurrence, but also as regards the meaning or idea which 
it represents in the world of phenomena.” 
The most wonderful and characteristic attribute of living organisms is 
their active adaptation to external and internal conditions in such a way 
as tends to the welfare of the individual or of the species. Of the count- WELCH: ADAPTATION IN PATHOLOGY. 
3 
less physiological examples which might be cited to illustrate this prin- 
ciple, I select, almost at random, the preservation of the normal temper- 
ature of the body in warm-blooded animals under varying external 
temperatures and varying internal production of heat, the regulation of 
respiration according to the need of the tissues for oxygen, the influence 
of the load upon the work performed by muscles, the accommodation of 
the heart to the work demanded of it, the response of glands to increased 
functional stimulation, the adjustment of the iris to varying degrees of 
illumination, the influence of varying static conditions upon the internal 
architecture of bone. 
The most striking characteristic of these countless adaptations is their 
apparent purposefulness. Even if it be true, as has been said by Lange, 
that “ the formal purposefulness of the world is nothing else than its 
adaptation to our understanding,” it is none the less true that the human 
mind is so constituted as to desire and seek an explanation of the adap- 
tations which it finds everywhere in organic nature. From the days of 
Empedocles and of Aristotle up to the present time there have been 
two leading theories to explain the apparent purposefulness of organic 
nature—the one, the teleological, and the other, the mechanical theory. 
The teleological theory, in its traditional signification, implies something 
in the nature of an intelligence working for a predetermined end. So 
far as the existing order of nature is concerned, the mechanical theory 
is the only one open to scientific investigation, and it forms the working 
hypothesis of most biologists. This theory, in its modern form, seeks 
an explanation of the adaptations of living beings in factors concerned 
in organic evolution. AVhat these factors are we know only in part. 
Those which are most generally recognized as operative are variation, 
natural selection, and heredity. That additional factors, at present little 
understood, are concerned seems highly probable. The acceptance of 
the explanation of physiological adaptations furnished by the doctrine 
of organic evolution helps us, I believe, in the study of pathological 
adaptations. 
As the word “ teleology ” has come to have, in the minds of many, so 
bad a repute in the biological sciences, and as I desire, without entering 
into any elaborate discussion of the subtle questions here involved, to 
avoid misconceptions in discussing subjects whose ultimate explanation is 
at present beyond our ken, I shall here briefly state my opinion that all of 
those vital manifestations to which are applied such epithets as adaptive, 
regulatory, regenerative, compensatory, protective, are the necessary 
results of the action of forms of energy upon living matter. The final 
result, however useful and purposeful it may be, in no way directly influ- 
ences the chain of events which leads to its production, and, therefore, 
the character of the result affords no explanation whatever of the mech- 
anism by which the end, whether it appear purposeful or not, has been 4 
WELCH: ADAPTATION IN PATHOLOGY. 
accomplished. In every case the ultimate aim of inquiry is a mechan- 
ical explanation of the process in question. Notwithstanding valuable 
contributions, especially within recent years, toward such mechanical 
explanations, we are still far removed from the attainment of this aim. 
The knowledge of the fact that the living body is possessed of means 
calculated to counteract the effects of injurious agencies which threaten 
or actually damage its integrity must have existed as long as the knowl- 
edge of injury and disease, for the most casual observation teaches that 
wounds are repaired and diseases are recovered from. It is no part of 
my present purpose to trace the history of the numerous speculations or 
even of the development of our exact knowledge concerning the subjects 
here under consideration. I cannot refrain, however, from merely re- 
ferring to the important role which the conception of disease as in some 
way conservative or combative in the presence of harmful influences has 
played from ancient times to the present in the history of medical doc- 
trines. Whole systems of medicine have been founded upon this concep- 
tion, clothed in varying garb. There is nothing new even in the image, 
so popular nowadays, representing certain morbid processes as a struggle 
on the part of forces within the body against the attacks of harmful 
agents from the outer world. Indeed, Stahl’s whole conception of disease 
was that it represented such a struggle between the anima and noxious 
agents. What lends especial interest to these theories is that then, as 
now, they profoundly influenced medical practice and were the origin of 
such well-known expressions as vis medicatrix naturae and medicus est min- 
ister naturae. 
It is needless to say that there could be no exact knowledge of the 
extent of operation or of the nature of processes which restore or com- 
pensate damaged structures and functions of the body or combat injuri- 
ous agents, before accurate information was gained of the organization 
and workings of the body in health and in disease. Although the way 
was opened by Harvey’s discovery of the circulation of the blood, most 
of our precise knowledge of these subjects has been obtained during the 
present century, through clinical observations and pathological and 
biological studies. In the domain of infectious diseases wonderful and 
hitherto undreamed of protective agencies have been revealed by modern 
bacteriological discoveries. Here, as elsewhere in medicine, the experi- 
mental method has been an indispensable instrument for discoveries of 
the highest importance and for the comprehension of otherwise inexpli- 
cable facts. Very interesting and suggestive results, shedding light 
upon many of the deeper problems concerning the nature and power of 
response of living organisms to changed conditions have been obtained 
in those new fields of experimental research called by Roux the mechanics 
of development of organisms, and also in part designated physiological 
or experimental morphology. Although we seem to be as far removed 5 
WELCH: ADAPTATION IN PATHOLOGY. 
as ever from the solution of the most fundamental problem in biology, 
the origin of the power of living beings to adjust themselves actively to 
internal and external relations, we have learned something from these 
investigations as to the parts played respectively by the inherited organ- 
ization of cells and by changes of internal and external environment in 
the processes of development, growth, and regeneration. 
In physiological adaptations, such as those which have been mentioned, 
the cells respond to changed conditions to meet which they are especially 
fitted by innate properties, determined, we must believe, in large part by 
evolutionary factors. In considering pathological adaptations the ques- 
tion at once suggests itself whether the cells possess any similar peculiar 
fitness to meet the morbid changes concerned; whether, in other words, 
we may suppose that evolutionary factors have operated in any direct 
way to secure for the cells of the body properties especially suited to meet 
pathological emergencies. Can we recognize in adaptive pathological 
processes any manifestations of cellular properties which we may not 
suppose the cells to possess for physiological uses ? This question appears 
to me to be of considerable interest. I believe that it can be shown that 
most pathological adaptations have their foundation in physiological 
processes or mechanisms. In the case of some of these adaptations, 
however, we have not sufficiently clear insight into the real nature of 
the pathological process nor into all of the physiological properties of 
the cells concerned to enable us to give a positive answer to the question. 
While we must believe that variation and natural selection combined 
with heredity have been important factors in the development and main- 
tenance of adjustments to normal conditions of environment, it is diffi- 
cult to see how they could have intervened in any direct way in behalf 
of most pathological adaptations. 
An illustration will make clear the points here involved. Suppose 
the human race, or any species of animal, to lack the power to compen- 
sate the disturbance of the circulation caused by a damaged heart-valve, 
and that an individual should happen to be born with the exclusive 
capacity of such compensation. The chances are that there would arise 
no opportunity for the display of this new capacity, and it is inconceiv- 
able that the variety would be perpetuated through the operation of the 
law of survival of the fittest by natural selection, unless leaky or clogged 
heart-valves became a common character of the species. When, how- 
ever, we learn that the disturbance of circulation resulting from disease 
of the heart-valves is compensated by the performance of increased work 
on the part of the heart, and that it is a general law that such prolonged 
extra work leads to growth of muscle, we see at once that this compen- 
sation is only an individual instance of the operation of a capacity which 
has abundant opportunities for exercise in normal life where the influ- 
ence of natural selection and other factors of evolution can exert their 
full power. 6 
welch: adaptation in pathology. 
In a similar light we can regard other compensatory and functional 
pathological hypertrophies—indeed, I believe, also to a considerable 
extent the pathological regenerations, inflammation, and immunity, 
although here the underlying factors are, of course, different. 
We may, however, reasonably suppose that natural selection may be 
operative in securing protective adjustments, such as racial immunity, 
against morbific influences to which living beings are frequently exposed 
for long periods of time and through many generations. 
These considerations help us to explain the marked imperfections of 
most pathological adaptations as contrasted with the perfection of physi- 
ological adjustments, although I would not be understood to imply that 
the absence of the direct intervention of natural selection in the former 
is the sole explanation of this difference. The cells are endowed with 
innate properties especially fitted to secure physiological adaptations. No 
other weapons than these same cells does the body possess to meet 
assaults from without, to compensate lesions, to restore damaged and lost 
parts. But these weapons were not forged to meet the special emergen- 
cies of pathological conditions. Evolutionary factors have not in gen- 
eral intervened with any direct reference to their adaptation to these 
emergencies. Such fitness as these weapons possess for these purposes 
comes primarily from properties pertaining to their physiological uses. 
They may be admirably fitted to meet certain pathological conditions, 
but often they are inadequate. Especially do we miss in pathological 
adjustments that co-ordinated fitness so characteristic of physiological 
adaptations. So true is this that the propriety of using such terms as 
compensation and adaptation for any results of pathological processes 
has been questioned. 
A heart hypertrophied in consequence of valvular lesion does not 
completely restore the normal condition of the circulation. Experience 
has shown that a kidney hypertrophied in consequence of deficiency of 
the other kidney is more susceptible to disease than the normal organ. 
What an incomplete repair of defects is the formation of scar-tissue, 
and with what inconveniences and even dangers may it be attended in 
some situations! If we look upon inflammation as an attempt to repair 
injury, and, therefore, as an adaptive process, with what imperfections 
and excesses and disorders and failures is it often associated! How 
often in some complex pathological process, such as Bright’s disease or 
cirrhosis of the liver, can we detect some adaptive features, attempts at 
repair or compensation, but these overshadowed by disorganizing and 
harmful changes. 
It is often difficult to disentangle in the complicated processes of dis- 
ease those elements which we may appropriately regard as adaptive from 
those which are wholly disorderly and injurious. There are usually two 
sides to the shield, and one observer from his point of view may see only WELCH: ADAPTATION IN PATHOLOGY. 
the side of disorder, and another from a different point of view, only 
that of adaptation. 
The conception of adaptation in a pathological process is not wholly 
covered by that of benefit to the individual. I understand, as has 
already been said, by an adaptive pathological process one which in its 
results brings about some sort of adjustment to changed conditions. 
This adjustment is usually, wholly or in part, advantageous to the indi- 
vidual ; but it is not necessarily so, and it may be harmful. The closure 
of pathological defects by new growths of tissue is a process which must 
be regarded as adaptive. But one would hardly describe as advantageous 
the scar in the brain which causes epilepsy. A new growth of bone to 
fill in defects is often highly beneficial; but what grave consequences 
may result from thickening of the skull to help fill the space left by 
partial arrest in development of the braiu in embryonic life or infancy! 
We see here, as everywhere, that “ Nature is neither kind nor cruel, 
but simply obedient to law, and, therefore, consistent.” 
In turning now to the more special, but necessarily fragmentary, con- 
sideration of a few of the pathological processes in which adaptation, in 
the sense defined, is more or less apparent, I shall have in view the 
answers to those two questions, What is the meaning of the process? 
and How is it caused? which confront us in our investigation of all 
natural phenomena. At the outset it must be admitted that our insight 
into the nature of many of these processes is very imperfect, and that 
here answers to the world-old riddles Why? and How? are correspond- 
ingly incomplete and liable to err. 
Although almost all of the elementary morbid processes, even the 
degenerations and death of cells, may, under certain conditions of the 
body, serve a useful purpose—the pre-eminent examples of pathological 
adaptation, in the sense of restoration or compensation of damaged 
structure or function, or the direct destruction or neutralization of inju- 
rious agents, are to be found among the compensatory hypertrophies, 
the regenerations, and the protective processes. To this last ill-defined 
group I refer parasiticidal and antitoxic phenomena, and some of the 
manifestations of inflammation, and perhaps also of fever. In the last 
analysis these protective processes, no less than the others mentioned, 
must depend upon the activities of cells. 
As it is manifestly impossible within the limits of a general address 
to attempt a detailed consideration of any large number of these adap- 
tive pathological processes, and as such consideration would necessarily 
involve the discussion of many technical and doubtful points, I have 
thought that my purpose would be best served by the selection of a few 
representative examples. 
The compensatory hypertrophies afford admirable illustrations of 
certain fundamental principles regarding adaptations in pathology 8 
WELCH: ADAPTATION IN PATHOLOGY. 
which I have already stated. The hypertrophy secures a functional 
adjustment, often of a highly beneficial character, to certain morbid 
conditions. This useful purpose is attained by a succession of events 
determined from beginning to end by the necessary response of cells and 
tissues, in consequence of their inherent organization, to the changed 
conditions. Given the changed conditions, on the one hand, and the 
organization of the cells, on the other, the result must follow as surely 
as night follows day, and this final result influences the preceding series 
of events no more in the one case than in the other. That the cells 
possess the particular organization determining the manner of their re- 
sponse to these changed conditions, and, therefore, the beneficial char- 
acter of the result, is dependent upon innate properties whose fitness for 
the purpose doubtless has been largely fixed by evolutionary factors, 
operating, however, mainly in behalf of physiological functions and not 
directly toward pathological adjustments. In correspondence with this 
view we find that our knowledge of the manner of production of the 
compensatory hypertrophies of various organs and tissues stands in direct 
relation to our knowledge of the physiology of the same organs and 
tissues. 
Those compensatory hypertrophies into the mechanism of whose pro- 
duction we have the clearest insight are referable to increased functional 
activity, and are, therefore, spoken of as work-hypertrophies. This has 
been proved for the muscular hypertrophies and compensatory hyper- 
trophy of the kidney; but the demonstration is not equally conclusive 
for the compensatory hypertrophy of other glands. I know, however, 
of no instance in which this factor in the explanation can be positively 
excluded. 
The relationship between increased functional activity and hyper- 
trophy is so evident in many cases that there is strong presumption in 
favor of this explanation of those glandular compensatory hypertrophies 
which have not as yet been clearly referred to the class of functional 
hypertrophies. The very occurrence of compensatory hypertrophy of 
an organ may direct attention to the fact that it is endowed with definite 
functions, and the conditions under which the hypertrophy occurs may 
shed light upon the nature of these functions. I need only remind you 
of the significance from this point of view of the compensatory hyper- 
trophy of the thyroid, adrenal, pituitary, and other glands with internal 
secretions. I fail to see why Nothnagel should consider a priori improb- 
able the occurrence of compensatory hypertrophy of one sexual gland 
after loss of the other, even before sexual maturity, or why Ribbert, who 
has apparently demonstrated experimentally such an occurrence, should 
find it necessary to seek the explanation in reflex nervous influences or 
mere hypericinia. The so-called secondary sexual characters and the 
changes following castration, including the influence upon a hyper- WELCH: ADAPTATION IN PATHOLOGY. 
9 
trophied prostate, point to important, even if little understood, func- 
tions which for the present we can perhaps best attribute to so-called 
internal secretions of these sexual organs. 
The name compensatory hypertrophy is sometimes applied to growths 
of tissue that merely take the place of another kind of tissue which has 
fallen out, as, for example, the growth of adipose tissue around a 
shrunken kidney or pancreas, or between atrophied muscle-fibres. Here 
there is only compensation of space, but no compensation of structure 
or function. Such hypertrophies and growths are described better as 
complementary than compensatory. 
Familiar examples of pathological hypertrophies from increased work 
are the hypertrophy of the heart from valvular disease and other causes, 
that of the muscular coats of canals and bladders behind some obstruc- 
tion, and that of one kidney after loss or atrophy of the other. 
In order to understand fully the manner of production of work-hyper- 
trophy of a part resulting from some morbid condition, it is essential to 
know the nature of the disturbances induced by the underlying morbid 
condition, how these disturbances excite increased functional activity of 
the part which becomes hypertrophied, and what the relation is between 
this greater activity and the increased growth of the part. 
It is impossible on this occasion to go through the whole list of com- 
pensatory hypertrophies with reference to the application of these prin- 
ciples. In no instance can the requirements stated be completely met in 
the present state of our knowledge. It will suffice for an understanding 
of the principles involved, and it is only with these that I am now con- 
cerned, if I take a concrete example. I select the classical and best 
studied one—compensatory hypertrophy of the heart. I trust that I 
shall be pardoned for selecting so commonplace an illustration, as the 
main points involved must be familiar to most of my audience; but it is 
possible that the application made of them may not be equally familiar. 
The only matters essential to my present line of argument are the 
mechanism of production of the hypertrophy and the general character 
of the adaptation thereby secured. 
The heart, like other organs of the body, does not work ordinarily up 
to its full capacity, but it is capable of doing at least three or four times 
its usual work. The excess of energy brought into play in doing this 
extra work is called conveniently, although not without some impro- 
priety, “ reserve force.” It has been proved experimentally that this 
storehouse of reserve power is sufficient to enable the healthy heart, at 
least that of a dog, to accommodate itself at once or after a few beats to 
high degrees of insufficiency or obstruction at its valvular orifices with- 
out alteration in the mean pressure and speed of the blood in the arte- 
ries. But even so tireless and accommodating an organ as the heart 
cannot be driven at such high pressure without sooner or later becoming 10 
WELCH: ADAPTATION IN PATHOLOGY. 
fatigued, and consequently so dilated as to fail to meet the demands upon 
it. If it is to continue long the extra work, it must receive new incre- 
ments of energy. 
The cardiac muscle is far less susceptible to fatigue than the skeletal 
muscles, but that it may become fatigued seems to me clear. 
Leaving out of consideration some doubtful causes of cardiac hyper- 
trophy, such as nervous influences, the various morbid conditions which 
lead to this affection are such as increase either the volume of blood to 
be expelled with each stroke, or the resistance to blood-flow caused by 
the pressure in the arteries or by narrowing at one of the valvular ori- 
fices, or both. Unless some regulating mechanism steps in, each of 
these circulatory disturbances must increase the resistance to contraction 
of the cardiac muscle, and it is evident that the heart must do extra 
work if it is to pump the blood through the arteries with normal pressure 
and speed. It is, however, no explanation of this extra work simply to 
say that it occurs because there is demand for it. Increased work by 
the heart in cases of disease of its nutrient arteries would often meet a 
most urgent demand on the part of the body, but here the heart flags 
and fails. 
The physiologists have given us at least some insight into the mechan- 
ism by which the heart responds through increased work to the circula- 
tory disturbances which have been mentioned. These disturbances all 
increase the strain on the wall of one or more of the cavities of the 
heart; in other words, increase the tension of the cardiac muscle, in 
much the same way as a weight augments the tension of a voluntary 
muscle. Now it is a fundamental physiological law that with a given 
stimulus greater tension of a muscle, within limits, excites to more pow- 
erful contraction, and thus to the performance of greater work. It 
seems clear that this law applies to the muscle of the heart, as well as 
to voluntary muscle. We do not know precisely how increased tension 
facilitates the expenditure of greater muscular energy. 
Another well-known fact in the mechanics of muscle is of importance 
in this connection. With increase of muscular tension under a given 
stimulus a point is reached where the extent of contraction is dimin- 
ished, although the mechanical work done, determined by multiplying 
the height to which the load is lifted by the weight of the load, is 
increased. This law applied to the heart, whose contractions are always 
maximal for the conditions present at any given time, signifies that, with 
increased resistance to the contraction of the muscular wall of one of its 
cavities, this cavity will empty itself during systole less completely than 
before. In other words, dilatation occurs, and, as has been shown by 
Roy and Adami, to whom we owe important contributions on this as well 
as on many other points relating to the mechanics of the heart, dilatation 
regularly antedates hypertrophy. This primary dilatation, however, is welch: adaptation in pathology. 
11 
not to be looked upon as evidence of beginning heart-failure, for, as 
these investigators have pointed out, it is within limits only an exagger- 
ation of a physiological condition, and can be subsequently overcome by 
hypertrophy, which, in consequence of increase in the sectional area of 
the muscle, lessens the strain upon each fibre, and thereby permits it to 
shorten more during contraction. If this result is completely secured, 
we have simple hypertrophy. More often the dilatation remains, and 
must necessarily remain, and we have excentric hypertrophy, which 
secures, for a time at least, adequate, but I do not think we can say per- 
fect, compensation. 
The weight of existing evidence favors the view that the power of the 
heart to adapt its work to the resistance offered resides primarily in its 
muscle-cells, and not in intrinsic or extrinsic nervous mechanisms, 
although doubtless these latter in various ways, which cannot be here 
considered, influence and support this regulating capacity. Nor can I 
here pause to discuss the influence of blood-supply to the cardiac muscle 
upon the force of ventricular contraction, although Porter has demon- 
strated that this is important. 
In tracing the steps from the primary morbid condition to the final 
hypertrophy, we have thus far had to deal mostly with known mechan- 
ical factors. We now come to the question, How does increased func- 
tional activity lead to increased growth ? 
Inasmuch as greater functional activity is regularly associated with 
a larger supply of blood to the more active part, -the view is advocated 
by many that the increased growth is the direct result of this hyperse- 
mia, and one often encounters, especially in biological literature, this 
opinion expressed as if it were an indisputable fact. There is, however, 
no conclusive proof of this doctrine, and many facts speak against it. 
The examples from human pathology commonly cited to support the doc- 
trine that local active hypersemia incites growth of cells are, so far as I 
am able to judge, complicated with other factors, such as injury, inflam- 
mation, or trophic disturbances. Transplantation-experiments, such as 
John Hunter’s grafting the cock’s spur upon the cock’s comb, sometimes 
adduced in this connection, are not decisive of this question, for here a 
new circumstance is introduced which some suppose to be the determining 
one for all morbid cell-growth, namely, the disturbance of the normal equi- 
librium between parts. Local active hypersemia may exist for a long 
time without evidence of increased growth in the congested part. To 
say that the hypersemia must be functional is at once to concede that it 
is not the sole factor. Experiments from Bizzozero’s laboratory, by 
Morpurgo and by Penzo, indicate that local hypersemia due to vaso- 
motor paralysis, or to the application of heat, favors cell-multiplication 
in parts where proliferation of cells is a normal phenomenon or is present 
from pathological causes, but that it is incapable of stimulating to 12 
welch: adaptation in pathology. 
growth cells whose proliferating power is suspended under physiological 
conditions, as in developed connective tissue, muscles, and the kidneys. 
It has been usually assumed that the way in which local hypersemia 
may stimulate cell-growth is by increasing the supply of nutriment to 
cells. The trend of physiological investigation, however, indicates that 
the cell to a large extent regulates its own metabolism. If the cell needs 
more food, of course it cannot get it unless the supply is at hand, and 
in this sense we can understand how a larger supply of blood may be 
essential to increased growth, but this is a very different thing from say- 
ing that the augmented blood-supply causes the growth. 
It is by no means clear that the question as to the influence of 
increased blood-supply upon cell-growth is identical with that of 
increased lymph-supply. The experiments of Paschutin and of Em- 
minghaus, from Ludwig’s laboratory, nearly a quarter of a century ago, 
indicate that local hypersemia due to vasomotor paralysis does not, as a 
rule, increase the production of lymph ; and more recent experiments, 
although not wholly concordant in their results upon this point, tend to 
the same conclusion. Functional activity, however, has a marked influ- 
ence in increasing the quantity and affecting the quality of lymph in 
the active part. Our knowledge of the physical and chemical changes 
in working muscles and glands enables us to conceive why this should 
be so, for all are now agreed that the formation of lymph is due not 
simply to filtration from the blood-plasma, but also to diffusion, and 
some believe likewise to active secretion by the capillary endothelium. 
Doubtless arterial hypersemia is essential to the maintenance of the 
increased flow of lymph in working organs. 
There are difficulties in the way of supposing that increased supply 
of lymph in itself furnishes the explanation of cell-growth, and especi- 
ally of that which characterizes hypertrophy of muscles and glands. 
Pathologists have frequent opportunities to study the effects of all 
degrees of increased production and circulation of lymph associated 
with venous hyperaemia. A kidney or a muscle may from this cause be 
subjected for months and years to an excess of lymph-flow, but there is 
no demonstration of any consequent hypertrophy or hyperplasia of renal 
epithelium or muscle-cell. It is true that the chemical composition of 
the lymph is not the same as that of lymph resulting from increased 
function, and it is possible that in this chemical difference lies the kernel 
of the whole matter. It may also be urged that in venous hyperaemia 
there are circumstances which restrain or prevent growth. Neverthe- 
less, if overfeeding, merely in consequence of increased supply of nutri- 
ment, were the real explanation of work-hypertrophies, one would expect 
to find some evidence of this in the class of cases mentioned. 
Ribbert has recently given a new shape to the doctrine that local 
hypersemia excites growth. While rejecting the usual explanation that WELCH: ADAPTATION IN PATHOLOGY. 
13 
it does so by supplying more food, he contends that distention of the 
bloodvessels and lymph-spaces, by mechanically disturbing the mutual 
relations of parts, removes obstacles to growth. This theory cannot be 
advantageously discussed until the fact is first established that uncom- 
plicated local hypersemia does incite growth. 
As the matter now stands, it seems to me that any satisfactory expla- 
nation of the cell-growth causing work-hypertrophies must start from 
physical or chemical changes in the muscle- or gland-cell itself directly 
connected with the increased function. These changes are the primurn 
mobile, and, however important increased supply of blood or lymph may 
be in the subsequent chain of events, it is not the determining factor. 
The whole problem is part of the general one of the causes of patholog- 
ical cell-growth, to which I shall have occasion to refer again. 
It is interesting to note that not all kinds of excess of functional 
activity lead to hypertrophy. A heart may beat for years faster than 
normal without becoming hypertrophied. Small movements of muscle, 
often repeated, do not cause hypertrophy. It would appear that the 
amount of work done in each functional act must attain a certain 
height in order to stimulate growth. On the other hand, if the muscle 
be stretched beyond certain limits, it does not hypertrophy ; on the con- 
trary, it may atrophy, as may be seen in greatly distended canals and 
cavities with muscular walls. This behavior is also in accordance with 
physiological observations. 
The compensatory hypertrophy of muscle seems to be due mainly to 
increase in the size of cells, although there are observations indicating 
that they may also multiply. That of most glands is referable to in- 
crease both in number and size of cells. Within four or five days after 
extirpation of a kidney karyokinetic figures may be found in increased 
number in the cells of the remaining kidney. 
The general character of the adaptation secured by compensatory 
hypertrophy of the heart is sufficiently well known. I wish to point 
out certain of its imperfections. I shall not dwell upon the well-known 
abnormal conditions, with their remote consequences, of the systemic or 
pulmonary circulation, which are present during the stage of compen- 
sation, nor shall I speak of the various circumstances which may inter- 
fere with the establishment of compensatory hypertrophy. 
The muscle of a hypertrophied heart is sometimes compared to that 
of the blacksmith’s arm, and the statement is made that there is no 
reason inherent in the muscle itself why the one should fail more than 
the other. This may be true, but it is not self-evident. Exercise may 
influence in various ways the nutrition, function, and growth of muscle 
as well as of other parts. Mere increase in bulk is a coarse effect. 
Quality may be improved as well as quantity. The biggest muscle is 
not necessarily the best or the most powerful. As every trainer knows, 
various conditions under which work is done influence the result. In- 14 
WELCH: ADAPTATION IN PATHOLOGY. 
crease in the reserve energy of the heart, secured by judicious exercise— 
and this is the main factor in endurance—probably cannot be attributed 
mainly to hypertrophy ; indeed, enlargement of this organ from exercise 
is often a serious condition. Much more might be said in this line of 
thought, but I have indicated why it seems to me unjustifiable to assume, 
without further evidence, that the condition of the muscle in patholog- 
ical hypertrophies is necessarily identical in all respects with that in 
physiological hypertrophies. 
There is an important difference in the working-conditions between 
most hypertrophied hearts and the normal heart. Although the maximal 
available energy of a hypertrophied heart during compensation is greater 
than that of the normal heart, clinical experience shows that in the 
majority of cases the energy available for unusual demands—that is, the 
so-called reserve force—is less in the former than in the latter. Some- 
times, especially when the hypertrophy has developed in early life, the 
hypertrophied heart is at no disadvantage in this respect. As pointed 
out with especial clearness by Martius, the significance of this alteration 
in the ratio normally existing between the energy expended for ordinary 
needs and that available for unusual demands, is that it furnishes an 
explanation of the greater liability of the hypertrophied heart to tire 
upon exertion. Fatigue of the heart is manifested by dilatation of its 
cavities, and when this dilatation from fatigue is added to that already 
existing in most cases, relative insufficiency of the mitral or tricuspid 
valve is likely to occur, and the compensation is, at least for a time, dis- 
turbed. The circulation through the coronary arteries, whose integrity 
is so important for the welfare of the heart, is impaired, and a vicious 
circle may be established. Notwithstanding the valuable contributions 
from the Leipzig clinic as to the frequency of various anatomical lesions 
in the muscle of hypertrophied hearts, it does not seem to me necessary 
to have recourse to them as an indispensable factor in the explanation of 
the breakage of compensation; but I shall not here enter into a discussion 
of the general subject of the causes of failure of compensation. 
I have described with some detail, although very inadequately, the 
manner of production of compensatory hypertrophy of the heart, in order, 
by this representative example, to make clear what seem to me to be 
certain general characteristics of many adaptive pathological processes, 
and I beg here to call attention especially to the following points. As has 
been emphasized by Nothnagel and others, no teleological idea or form 
of language need enter into the explanation of the mechanism of the 
process. The final result is the necessary consequence of the underlying 
morbid conditions. We have satisfactory mechanical explanations for 
essential steps in the process, and there is no reason to assume that other 
than mechanical factors are concerned in those vital manifestations which 
at present we are unable to explain by known physical and chemical 
forces. The properties of the cells which determine the character of 15 
WELCH: ADAPTATION IN PATHOLOGY. 
their response to the changed conditions are none other than their well- 
known physiological properties. The adaptation finally secured, admir- 
able as it is in many respects, and perhaps adequate for a long and active 
life, is generally attended with marked imperfections, and, strictly speak 
ing, is not a complete compensation. It does not present that co-ordinate 
and special fitness which we are accustomed to find in physiological adap- 
tations, for the explanation of which so much has been gained by the 
study of the factors concerned in organic evolution. 
It may be argued that under the circumstances no better kind or 
degree of adaptation can be conceived of than that which actually 
occurs, and that the operation of evolutionary factors, with especial refer- 
ence to the adjustment of the organism to the conditions causing cardiac 
hypertrophy, could not secure any better result. I think that it is not 
difficult to conceive how improvements might be introduced. It is, 
however, permissible to suppose that the introduction into the workings 
of the organism of some better mechanism to compensate the morbid 
conditions might be at the sacrifice of more important physiological 
attributes of the body. More perfect pathological adaptations might in 
many instances involve a deterioration of the physiological characters 
of the species. It is often the case that the more highly organized 
living beings lack some capacity possessed by those lower in the scale of 
organization to resist or compensate injury and disease. This is notably 
true of the power to regenerate lost parts. It is, however, along the 
lines of improvement in the physiological characters of the individual 
or species that the opportunity often lies for securing increased resist- 
ance to disease or better pathological adaptations. 
It would be interesting to continue our consideration of the compensa- 
tory hypertrophies by an examination of those of glandular organs from 
points of view similar to those adopted for the heart. For the kidney, 
at least, the materials are at hand for such a purpose; but, as I desire in 
the limited time at my disposal to touch upon other varieties of path- 
ological adaptation, I must refer those interested especially to the inves- 
tigations of Grawitz and Israel, Ribbert, Nothnagel, and Sacerdotti as 
to the conditions underlying compensatory hypertrophy of the kidney. 
I can likewise merely call attention to the interesting researches of 
Ponfick upon the most wonderful of the compensatory hypertrophies in 
higher animals, that of the liver. Ponfick, as is well known, has demon- 
strated that after removal of three-fourths of this organ new liver- 
substance, with normal functions, is recreated from the remainder and 
to an amount nearly equalling that which was lost. 
The chapter of pathological adaptations in bones and joints I shall 
leave untouched, notwithstanding the admirable illustrations which 
migiit be drawn from this domain. 
There is no more fascinating field for the study of pathological adap- 
tations with reference to the mechanical factors involved than that fur- 16 
WELCH: ADAPTATION IN PATHOLOGY. 
nished by the bloodvessels, as has been shown especially by the brilliant 
researches of Thoma. With wonderful precision can a vessel or system 
of vessels adjust itself to changes in the pressure, velocity, and quantity 
of blood, and thereby serve the needs of the tissues for blood. Under 
pathological, as well as physiological, conditions this adjustment may be 
brought about not only through the agency of vasomotor nerves and 
the physical properties of the vascular wall, but also, when the necessity 
arises, by changes in the structure of the wall. 
The changes in the circulation introduced by the falling out of the 
placental system at birth are essentially the same as those resulting from 
amputation of an extremity, and the consequent alterations in the struc- 
ture of the umbilical artery are identical with those in the main artery 
of the stump after amputation. The closure of the ductus Botalli and 
the ductus venosus soon after birth, and, still better, transformations of 
vessels in the embryo, furnish physiological paradigms for the develop- 
ment of a collateral circulation. Many other illustrations might be 
cited, did time permit, to show that in the processes of normal develop- 
ment, growth and regressive metamorphosis of parts, both before and 
after birth, and in menstruation and pregnancy, changed conditions of 
the circulation arise analogous to certain ones observed under pathologi- 
cal circumstances, and that the mode of adjustment to these changes 
by means of anatomical alterations in the vessels may be essentially the 
same in the physiological as in the morbid state. I see in these facts an 
explanation of the relative perfection of certain vascular adaptations to 
pathological or artificial states, as may be exemplified by changes in a 
ligated artery and by the development of a collateral circulation. The 
mechanisms by which the adjustments are secured have, in consequence 
of their physiological uses, for reasons already explained, a special 
fitness to meet certain pathological conditions. That this fitness should 
be greater in youth than in old age is in accordance with laws of life, 
indicated with especial clearness by Minot in his interesting studies on 
“ Senescence and Rejuvenation.” 
But these mechanisms are not equally well adapted to meet all mor- 
bid changes in the vessels. Although Thoma’s interpretation of the 
fibrous thickening of the inner lining of vessels in arteriosclerosis and 
aneurism as compensatory, or, as I should prefer to say, adaptive, is 
not accepted by all pathologists, it seems to me the best explanation in 
many cases. But the adaptation, if it be such, is here usually of a very 
imperfect nature, and it is not surprising that it should be so, when one 
considers the improbability of any mechanism developing under physio- 
logical conditions which should be specially fitted to meet the particular 
morbid changes underlying aneurism and arteriosclerosis. 
I shall not be able to enter into a consideration of the mechanical 
factors concerned in adaptive pathological processes in bloodvessels, 
although perhaps in no other field are to be found more pertinent illns- welch: adaptation in pathology. 
17 
trations of the views here advocated concerning pathological adapta- 
tions. The whole subject has been studied from the mechanical side 
most fully and ably by Thoma, whose four beautifully simple histo- 
mechanical principles are at any rate very suggestive and helpful work- 
ing-hypotheses, even if it should prove, as seems to me probable, that 
they are too exclusive. I shall call attention in this connection only 
to the inadequacy of the old and still often adopted explanation of 
the development of a collateral circulation. The rapidity with which 
a collateral circulation may be established after ligation of a large artery, 
even when the anastomosing branches are very small, is known to every 
surgeon. This was formerly attributed to increase of pressure above 
the ligature; but this rise of pressure has been shown to be too small to 
furnish a satisfactory explanation, and Nothnagel has demonstrated that 
there is little or no change in the calibre of arteries coming off close 
above the ligature unless they communicate with branches arising below 
the ligature. Von Recklinghausen several years ago suggested a better 
explanation. The bed of the capillary stream for the anastomosing 
arteries is widened by ligation of the main artery, inasmuch as the 
blood can now flow with little resistance from the capillaries of the 
anastomosing branches into those of the ligated artery. The result is 
increased rapidity of blood-flow in the anastomosing vessels. Accord- 
ing to one of Thoma’s histo-mechanical principles, increased velocity of 
the blood-current results in increased growth of the vessel-wall in super- 
ficies—that is, in widening of the lumen. The tension of the vessel- 
wall, which is dependent on the diameter of the vessel and the blood- 
pressure, is, according to Thoma, thus increased ; and, according to 
another of his principles, this greater tension results in growth of the 
vascular wall in thickness. The changes in the walls of the anastomos- 
ing vessels seem to me best interpreted as referable to a genuine work- 
hypertrophy, a conception which has already been advanced by Ziegler. 
The pathological regenerations constitute a large group of adaptive 
morbid processes of the highest interest. Their study has become almost 
a specialized department of biology, and occupies a very prominent 
place in the extensive literature of recent years relating to experimental 
or physiological morphology. It has revealed in unexpected ways the 
influence of external environment upon the activities of cells, as is 
illustrated in a very striking manner by Loeb’s studies of heteromor- 
phosis. 
Although the capacity to regenerate lost parts must reside in the 
inherited organization of the participating cells, there are observations 
which seem to indicate that in the lower animals this capacity may exist 
independently of any opportunity for its exercise during any period of 
the normal life of the individual or species or their ancestors, including 
the period of embryonic development. This is the inference which has 
been drawn from Wolff’s observation, that after complete extirpation of 18 
WELCH: ADAPTATION IN PATHOLOGY. 
the ocular lens with the capsular epithelium in the larval salamander, a 
new lens is reproduced from the posterior epithelium of the iris. There 
are other observations of similar purport. The acceptance of this infer- 
ence, however, seems to me to involve such difficulties that we may 
reasonably expect that further investigations will afford more satisfac- 
tory explanations of these curious and puzzling phenomena of regenera- 
tion. Of much interest and significance are the so-called atavistic 
regenerations, where the regenerated part assumes characters belonging 
not to the variety or species in which it occurs, but to some ancestral or 
allied species. For these and other reasons Driesch refers the patho- 
logical regenerations to what he calls the secondary self-regulations, by 
which term he designates those adjustments of artificially induced dis- 
turbances which are brought about by factors foreign to the normal 
development and life of the individual. 
The view advocated by Barfurth seems to me more probable, that the 
pathological regenerations depend upon cellular properties pertaining to 
the normal life of the organism. This view is supported by the fact 
that, with a few probably only apparent exceptions, the regenerations 
conform to the law of specificity of cells. The pathological regenerations 
occurring after birth can be referred to the retention in greater or less 
degree of formative powers possessed by the cells pre-eminently in 
embryonic life. These powers in general tend gradually to diminution 
or extinction as the individual grows older, although in some cells, such 
as the covering epithelium of the skin and mucous membranes, this loss 
of regenerative power with advancing years is scarcely manifest. Even 
after the cessation of growth the regenerative capacity is not wholly in 
abeyance under physiological conditions. Bizzozero has studied and 
classified the various tissues of the body according to the activity of 
their physiological regeneration. 
In general, the more highly differentiated and specialized a cell, the 
less is its capacity for regeneration ; but we now know that such differ- 
entiation is attended with less sacrifice of its regenerative power than was 
once supposed. Even such highly specialized cells as those of striped 
muscle are capable of regeneration. Indeed, the nerve-cells seem to be 
the only ones incapable of proliferation, and even this is not certain, for 
there are competent observers who claim that these cells may multiply, 
although there is no evidence that in the higher animals they can give 
rise to functionally active new nerve-cells. The ease with which a part 
of the nerve-cell, namely, its axis-cylinder process, can be regenerated is 
well known. 
The cell-proliferation in regeneration is attributed to the removal of 
resistance to growth in consequence of the defect resulting from loss of 
tissue. It has been pointed out, especially by Ziegler and by Ribbert, 
that not only cells in the immediate neighborhood of the defect multiply, 
but likewise those at such a distance that it is difficult to suppose that WELCH: ADAPTATION IN PATHOLOGY. 
19 
the latter have been directly influenced by the loss of tension in the 
tissues caused by the defect. Ziegler refers the proliferation of the dis- 
tant cells to compensatory hypertrophy, and Ribbert attributes it to 
hypenemia resulting from the presence in the defect of foreign materials, 
such as extravasated blood, exudation, and necrotic tissue. 
We are brought here, as we were in the consideration of the compen- 
satory hypertrophies, to one of the most fundamental and important 
questions in pathology—the causes of pathological cell-growth. The 
interpretation of many pathological processes as adaptive or not, hinges 
often upon opinions held concerning the underlying causes of cell- 
proliferation. The main question at issue is, How far one is willing to 
go in attributing cell-growth to primary defects in the tissue, and inter- 
preting the growth as for the purpose of regeneration or filling up a 
defect? Differences of opinion upon this subject are illustrated by the 
different interpretations of the cell-proliferations in acute and chronic 
inflammations, some pathologists considering these to be essentially 
regenerative and compensatory ; others regarding them, at least in large 
part, as directly incited by inflammatory irritants and not to be ranked 
wholly with the regenerative processes. 
The doctrine of Virchow was long accepted without question, that 
inflammatory cell-growth is the result of the action of external stimuli, 
the so-called inflammatory irritants, upon the cells, which are thereby 
directly incited to grow and multiply. The attack upon this doctrine 
has been most vigorously led by Weigert, who denies absolutely the 
power of any external agencies to stimulate directly cells to prolifera- 
tion. He considers that to concede such a bioplastic power to external 
agents is equivalent to the acceptance of a kind of spontaneous genera- 
tion of living matter. 
Weigert’s views upon this subject have undoubtedly had a most fruit- 
ful influence upon pathology. It has been such an influence as a good 
working-hypothesis, whether finally demonstrated to be true or not, has 
often had in the development of science. In putting to the test of actual 
observation Weigert’s hypothesis, we have been led to recognize the fre- 
quency and the importance of primary injuries to cells inflicted by 
external agencies. Not only various degenerations and necroses of 
entire cells, but more subtle and partial damage of cytoplasm and 
nucleus have been made the subject of special study. It has been recog- 
nized that our older methods of hardening tissues reveal often only very 
imperfectly the finer structure of cells, and new and better methods have 
been introduced which enable us to detect more delicate lesions of cell- 
substance which formerly escaped attention, as is well illustrated in 
recent studies in neuropathology. Weigert’s postulate of some primary 
injury to the tissues as the immediate effect of mechanical, chemical, 
and other external agencies, which were formerly regarded as the direct 
stimuli of cell-growth and multiplication, has been fulfilled in many 20 
WELCH: ADAPTATION IN PATHOLOGY. 
instances where such damage had previously been overlooked or unsus- 
pected. It is his belief that in cases where we cannot now detect such 
primary injury more thorough search and better methods will enable us 
to do so. One may, of course, reasonably cherish such an expectation ; 
but at the same time we must recognize the fact that morbid cell-prolifer- 
ations occur under circumstances where we cannot at present associate 
them with any demonstrable injury to the tissues—indeed, in some cases 
where our insight into the structure of the part seems to be so clear and 
satisfactory that one is very reluctant to admit the existence of an unde- 
tected damage to the cells. 
Perhaps the most important modification of former pathological con- 
ceptions, resulting from the belief that cell-growth is caused by primary 
defects and injuries of tissue, relates to the chronic interstitial inflam- 
mations or fibroid processes. The older view that in these processes the 
active and essential feature of the disease is the new growth of connec- 
tive tissue, which strangled the more highly organized cells of the part, 
has been replaced to a large extent by the opinion that the primary and 
most important lesion is the degeneration, atrophy, or necrosis of the 
more specialized cells, whose place is taken by the new growth of inter- 
stitial tissue. In many instances, as in fibroid patches in the myocar- 
dium, and in man}r scleroses of the central nervous system, this latter 
conception affords the best and most natural interpretation of the facts. 
There are, however, great difficulties in explaining all chronic interstitial 
inflammations by this doctrine, and I must take side with those who 
admit the occurrence, for example, in the kidney and in the liver, of 
primary interstitial inflammations characterized by proliferation of the 
connective tissue and endothelial cells. 
Indeed, it seems to me that Weigert’s formula is too narrow to cover 
all of the observed facts concerning cell-proliferation. Essential features 
of the theory that cells cannot be directly stimulated to growth by ex- 
ternal agents were present in Boll’s doctrine of border warfare between 
neighboring cells. Weigert’s presentation of this theory is in a far more 
acceptable shape than that of Boll. A still more comprehensive state- 
ment of the general theory is that cells are incited to growth through 
removal of obstacles to growth in consequence of some disturbance in 
the normal relations or equilibrium of the cells with surrounding parts. 
The capacity to proliferate must be present in the cells, but with the 
cessation of growth this capacity is rendered latent or potential by the 
establishment of definite relations or an equilibrium between cells and 
neighboring parts, including under the latter not only adjacent cells, but 
also basement-substance, lymphatics, bloodvessels, tissue-juices, chemical 
substances, etc. It is evident that under these circumstances in only 
two ways can the cells be incited to growth, either by removal of resist- 
ance or obstacles to growth, or by an increase in the formative energy 
resident within the cell, and that in either way energy must be used, WELCH: ADAPTATION IN PATHOLOGY. 
21 
whether it be employed to remove obstacles to growth or to increase the 
proliferative forces within the cell. 
It appears to me by no means an easy matter to decide in all cases in 
which of the two ways mentioned cell-proliferation is brought about. 
Removal of obstacles to growth, not only in the way indicated by 
Weigert, but also by other disturbances in the neighborhood-relations 
of the part, and very probably by the presence of definite chemical 
substances, may be the explanation of all pathological cell-growths. 
Certainly it would not be easy conclusively to disprove this view. 
Nevertheless, I fail to comprehend the inherent difficulties which some 
find in admitting the possibility of forms of energy, acting from with- 
out, directly increasing the formative energy of the cell; in other words, 
directly stimulating the cell to growth and multiplication. If such a 
possibility be admitted, the natural interpretation of some examples of 
cell-proliferation is that they are directly caused by the action of ex- 
ternal forces, in the sense advocated by Virchow. 
Students of the problems of pathological cell-growth must take into 
consideration not only the facts of human and allied pathology, but 
also those which are so rapidly accumulating in the domain of experi- 
mental embryology and morphology, to the importance of which I have 
repeatedly referred in this address. I would call attention especially to 
the observations from this source as to the influence of various changes 
of environment, particulai’ly of definite chemical, thermic, and mechan- 
ical changes in surrounding parts, upon the direction of movement and 
of growth of cells. The use at present made of chemotactic phenomena 
in explaining the direction of movement of cells in human pathological 
processes is only a very limited and inadequate application of these im- 
portant observations concerning tactic and tropic stimuli. We shall 
probably come to realize more and more the operation of these factors 
in determining cell-movements and cell-growth in human pathology. 
We already have evidence that different kinds of leucocytes not only 
possess different specific functions, but also respond in different ways to 
definite tactic stimuli. The long-standing problem of the lymphoid cell 
in inflammation approaches solution along these lines of investigation. 
A burning question, and one of perennial interest, relating to our sub- 
ject is: How far are we justified in regarding acute inflammation as an 
adaptive or protective morbid process? There is fair agreement as to 
the essential facts of observation, but regarding their interpretation there 
are wide differences of opinion, and when one considers the complexity 
of the process and its still unsolved riddles, it is not hard to see why 
this should be so. Much depends upon the point of view, and in this 
respect there can be recognized a certain antagonism between the purely 
clinical and the purely pathological and experimental views, an antag- 
onism, however, which must be reconciled by a full knowledge of the 
subject. 22 
WELCH: ADAPTATION IN PATHOLOGY. 
It is not likely that the purely clinical study of inflammation would 
ever lead to the idea that the general tendency of this process is advan- 
tageous to the patient. The more severe and extensive the inflammatory 
affection, the more serious, as a rule, is the condition of the patient. 
The surgeon sees his wounds do wrell or ill according to the character and 
extent of inflammatory complication. Measures directed to the removal 
of inflammatory exudation, such as the evacuation of pus from an abscess 
or an empyema, are the most successful methods of treatment, and the 
rules are embodied in ancient surgical maxims. How can one conceive 
of any purpose useful to the patient served by filling the air-cells of his 
lung with pus-cells, fibrin, and red corpuscles in pneumonia, or bathing 
the brain and spinal cord in serum and pus in meningitis ? If nature 
has no better weapons than these to fight the pneumococcus or meningo- 
coccus, it may be asked, “ What is their use but to drive the devil out 
with Beelzebub?” 
But the pathologist and bacteriologist sees another aspect of the pic- 
ture. An infectious micro-organism has invaded the tissues, where it 
multiplies and where its toxic products begin to work havoc with the 
surrounding cells, and by their absorption to cause constitutional symp- 
toms and perhaps damage to remote parts. Is the destructive process 
to go on without any defence on the part of the body? There is 
attracted to the injured part an army of leucocytes from the bloodves- 
sels, and perhaps other cells, from the neighboring tissues, and it has 
been conclusively shown that these cells can pick up foreign particles 
and remove them, and that they contain substances capable of destroy- 
ing many micro-organisms. At the same time serum accumulates in 
and around the injured area, and this may aid by its chemical properties 
in destroying bacteria, in diluting poisons, in flushing out the part. 
Fibrin may appear, and some think that this may serve in some situa- 
tions as a protective covering. If these agencies, hostile to the invading 
micro-organism, gain the upper hand, the debris is cleared away by pha- 
gocytes and other means, and the surrounding intact cells, which had 
already begun to multiply, produce new tissue vThich takes the place of 
that which had been destroyed. The victory, however, is not always 
with the cells and other defensive weapons of the body. The struggle 
may be prolonged, may be most unequal, may cover a large territory, 
and the characters and extent of the inflammation furnish an index of 
these different phases of the battle. 
Such in bald outlines are two divergent views of inflammation. 
I do not see how we can fail to recognize in that response to injury, 
which we call inflammation, features of adaptation. Inflammation may 
be in some cases the best response to secure the removal or destruction 
of injurious agents, but we cannot look upon it as the most perfect mode 
of protection of the body against invading micro-organisms. One may 
inoculate into three animals, even of the same species, but possessed of welch: adaptation in pathology. 
23 
different individual resistance, the same quantity of the same culture of 
a pathogenic micro-organism and obtain sometimes the following results : 
The first one will present no appreciable inflammatory reaction whatever, 
and no evidences of any other disturbance, and examination will show 
that the micro organisms have quickly disappeared. The second one 
will develop an extensive local inflammation and survive, but after a 
long illness. The third one will offer little resistance to the micro-organ- 
ism, which rapidly multiplies without causing marked inflammation, 
invades the blood or produces toxaemia, and quickly destroys the life of 
the animal. Now, it is evident that the best protective mechanism is 
that brought into action by the first animal, but that the inflammatory 
reaction set up in the second one is better than the absence of reaction 
and of other defences in the third animal. 
I can scarcely do more on this occasion than to indicate some of the 
points of view from which it seems to me that we can best approach the 
study of inflammation as an adaptive process. With inflammation, as 
with other adaptive processes, any useful purpose subserved affords no 
explanation of the mechanism of the process. We should guard against 
all ideas which introduce, even unconsciously, the conception of some- 
thing in the nature of an intelligent foresight on the part of the partici- 
pating cells. The response of these cells in inflammation is a necessary 
and inevitable one determined by their innate properties. Our efforts 
should be directed, in the first place, toward as near an approach as pos- 
sible to a mechanical explanation of inflammatory processes by a study, 
on the one hand, of the properties and mode of action of the causes of 
inflammation, and, on the other hand, of the nature and source of the 
cellular properties concerned. We may properly inquire whether these 
properties fit the cells to counteract the effects of injury, and if so, 
whence comes this fitness. Has the fitness those attributes of relative 
perfection which we find in most physiological adaptations, or is it char- 
acterized by the uncertainties and imperfections of so many pathological 
adaptations? Is the character of the response to injury in inflammation 
such as to indicate that the agencies concerned have acquired through 
evolutionary factors a special fitness to meet the pathological emergen- 
cies ? Are all or only a part of the manifestations of the inflammatory 
processes adaptive? 
It cannot be doubted that there are innate properties of certain cells 
called into action in inflammation, such as those manifested in the attrac- 
tion of leucocytes and other cells by definite chemical substances, the 
capacity of cell-proliferation from causes connected with injury, the 
power of phagocytosis and other bactericidal properties, which may be 
adapted to counteract the effects of injurious agents. When these forces 
bring about the prompt destruction or removal of the injurious sub- 
stances. and the defect is quickly repaired, the adaptation is complete 
and unmistakable. When, however, the inflammatory irritants and 24 
WELCH: ADAPTATION IN PATHOLOGY. 
their destructive effects persist, and the proliferation of cells and accu- 
mulation of inflammatory products become excessive and occupy large 
areas, the features of adaptation are not so easily recognized. The 
mere occupation of territory by inflammatory products is often a serious 
injury and it can be regarded as an adaptive feature only when they fill 
some artificial defect. Such occupation may be in itself enough to 
counteract any useful work in which these products may be engaged. 
We can reasonably seek in the relations of the body to the outer world 
an explanation of the development of certain properties of cells which 
serve a useful purpose in mechanical and other injuries. These proper- 
ties find application also in the normal life of the organism. Their 
exercise in response to injury imparts to inflammation important adap- 
tive or protective characteristics, but I fail to see in this process any 
such special fitness as would justify extravagant statements which have 
been made to the effect that inflammation ranks among the adaptations 
of living beings by the side of digestion and respiration. 
I have endeavored in this address to present certain general consid- 
erations concerning pathological adaptations. It has been possible to 
bring under consideration only a small part of an immense field, and 
this very inadequately. We have seen that in the sense in which adap- 
tation was defined we can recognize in the results of morbid processes 
frequent and manifold evidences of adjustment to changed conditions. 
These adjustments present all degrees of fitness. Some are admirably 
complete ; more are adequate, but far from perfect; many are associated 
with such disorder and failures that it becomes difficult to detect the 
element of adaptation. The teleological conception of a useful purpose 
in no case affords an explanation of the mechanism of an adaptive pro- 
cess. I have suggested that the adaptability of this mechanism to bring 
about useful adjustments has been in large part determined by the factors 
of organic evolution, but that in only relatively few cases can we sup- 
pose these evolutionary factors to have intervened in behalf of morbid 
states. For the most part, the agencies employed are such as exist 
primarily for physiological uses, and while these may be all that are 
required to secure a good pathological adjustment, often they have no 
special fitness for this purpose. 
The healing power of nature is, under the circumstances present in 
disease, frequently incomplete and imperfect, and systems of treatment 
based exclusively upon the idea that nature is doing the best thing pos- 
sible to bring about recovery or some suitable adjustment, and should 
not be interfered with, rest often upon an insecure foundation. The 
agencies employed by nature may be all that can be desired ; they may, 
however, be inadequate, even helpless, and their operation may add to 
existing disorder. There is ample scope for the beneficent work of the 
physician and surgeon. TOe Joiirijal 
of the MEDICAL SCIENCES. 
MONTHLY, $4.00 PER ANNUM. 
WITH 1897 The American Journal of the Medical Sciences enters upon its seventy- 
eighth year, still the leader of American medical magazines. In its long career it has 
developed to perfection the features of usefulness in its department of literature, and 
presents them in unrivalled attractiveness. It is the medium chosen by the leading minds 
of the profession on both sides of the Atlantic for the presentation of elaborate Original Articles; 
its Reviews are noted for discernment and absolute candor, and its Classified Summaries of 
Progress each month present an epitome of medical advances gleaned by specialists in the 
various departments. According to unquestionable authority, “ It contains many original papers 
of the highest value; nearly all the real criticisms and reviews which we possess, and such 
carefully prepared summaries of the progress of medical science and notices of foreign works that 
from this file alone, were all other publications of the press for the last fifty years destroyed, it 
would be possible to reproduce the great majority of the real contributions of the world to medical 
science during that period.” 
Tl)e Medical NeWs 
WEEKLY, $4.00 PER ANNUM. 
BY KEEPING closely in touch with the needs of the active practitioner, The News has 
achieved a reputation for utility so extensive as to render practicable its reduction in 
price from five to Four Dollars per annum. It is now by far the cheapest as well as 
the best large weekly medical journal published in America. Employing all the recognized 
resources of modern journalism, such as the cable, telegraph, resident correspondents, special 
reporters, etc., The News furnishes in the 28 quarto pages of each issue the latest and best infor- 
mation on subjects of importance and value to practitioners in all branches of medicine. Its 
numerous departments are designed to subdivide and present its material in the most attractive 
and convenient manner. 
In a word The Medical News is a crisp, fresh, weekly newspaper, and as such occupies a 
well-marked sphere of usefulness, distinct and complementary to the ideal monthly magazine, 
The American Journal of the Medical Sciences. 
The Year-Book of Treatment for 1897 
Gives a classified summary and review of the real advances in treatment made during 1894 in all 
departments of the science of medicine. Price, $1.50; or in combination with either or both the 
above journals, 75 cents. Ready early in 1897. 
The Medical News Visiting List for 1897 
Published in four styles: Weekly, dated, for 30 patients; Monthly, undated, for 120 patients per 
month; Perpetual, undated, for 30 patients weekly per year; Perpetual, for 60 patients weekly 
per year. The first three styles contain 32 pages of important data and 160 pages of assorted 
blanks; the 60-patient perpetual consists of 256 pages of blanks. Price, each, $1.25. In com- 
bination with either or both above periodicals, 75 cents. Or, Journal, News, Visiting List 
and Year-Book, #8.50. Thumb-letter index for Visiting List, 25 cents extra. 
LEA BROTHERS & CO., Publishers, 
706, 708 & 710 Sansom St., Phi la. 
Ill Fifth Ave. (cor. 18th St.). N. Y.