Cornell University Library Ithaca, New York BOUGHT WITH THE INCOME ©F THE SAGE ENDOWMENT FUND THE GIFT OF HENRY W. SAGE 1891 RETURN TO ALBERT R. MANN LIBRARY ITHACA, N. Y. OH 546. Mio University Library iii Cornell University Library The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924003092867 MEDICAL CONTRIBUTIONS TO THE STUDY OF EVOLUTION MEDICAL CONTRIBUTIONS TO THE STUDY OF EVOLUTION \ & BY eo’ Para J. G. ADAMI M.D., F.R.S., F.R.C.P. THE MACMILLAN COMPANY NEW YORK 8 & TO SIR T. CLIFFORD ALLBUTT K.C.B,, F.R.S., F.R.C.P. &o. PHYSICIAN, PHILOSOPHER, FRIEND WHO AS REGIUS PROFESSOR PRESIDED OVER THE DELIVERY OF THE HARLIEST OF THESE: STUDING IT AND ITS OFFSPRING PREFACE WuEN at the beginning of the Great War the invitation was tendered to me to deliver the time-honoured Croonian Lectures before the Royal College of Physicians of London, it was long months before I could determine my subject. During these months the burden of administrative work in connection with the Canadian Army Medical Service became progressively greater. Research in the laboratory was out of the question. My official duties at that period dealt largely with returns and statistics of invalidism, but soon it became apparent that months, if not years, must elapse before the vast mass of material being collected by the Medical Research Committee at the British Museum would be fully available. Inevitably, therefore, I was led to fall back upon previous studies, and, when still debating, a chance discussion with a leading British biologist convinced me that the time was ripe to bring together and sum up the conclusions regarding Adapta- tion which as a student of pathology I had reached gradually in the years preceding the War. I judged from the discussion above referred to that that earlier work was not known to biologists in general. Varied as is his reading and brilliant his memory, this distinguished biologist was evidently wholly ignorant concerning it. It seemed also that it would be serviceable to present the conclusions reached, not so much from the point of view of their medical bearing, as from that of their biological significance, in order that both morphologist and physician might observe the direction in which medical research is surely leading vii vill THE STUDY OF EVOLUTION us with reference to matters that form the basis of general biology. Hence the Croonian Lectures upon Adaptation and Disease, delivered in June 1917, which form the first part of this volume. . Elsewhere I have dealt with this subject of adaptation for the benefit of the student of medicine ;1 in dealing with the same subject more from the point of view of the biologist, I had of necessity to refer to and repeat data and deductions employed in my earlier writings. The views here enunciated have been arrived at in orderly sequence from the year 1891 onwards, and it has been difficult to review that sequence with- out employing the facts and arguments by which the successive steps were attained. While making this confession I have at the same time found myself confronted with the difficulty that, in compressing my treatment of the subject into four lectures, much that should have been dealt with in fuller detail, and with greater wealth of examples, has owing to the exigencies of space and time been unavoidably passed over very rapidly. To remedy this, and at the same time to demonstrate that no newly developed doctrine is here taught, but one arrived at and published many years ago, it has seemed advisable to reprint in their entirety ? certain earlier papers and addresses, all bearing upon adapta- tion and tissue modification, which establish and amplify the successive stages of my argument. These are useful as documents in the case. Personally, re-reading them after a lapse of many years, and so with some sense of detachment, they have struck me as to a certain extent entertaining. May their other readers have the same opinion, and obtain a like satisfaction ! It may be held that an apology is due to not a few well-known 1 Notably in the two editions of my Principles of Pathology in 1908 and 1910, but those are works of some thousands of pages; it is perhaps natural that biologists in general have been deterred from consulting them. 2 Save for slight structural alterations, advisable in converting delivered addresses from the spoken to the printed form. These alterations have been duly noted whenever it has seemed possible that there has been introduced thereby the slightest departure from the sense of the original. PREFACE ix British biologists, many of them for long years my personal friends, on the ground that my Croonian Lectures implied that I regard them all as “academic.” This, let me hasten to assure them, is very far from being the case. If these lectures be read with reasonable care it will be seen that no such charge is made. I was concerned not to cover the whole ground of modern in- vestigations upon the problems of evolution, but to show the bearing of medical research upon matters pertaining thereto. I realize full well that it would have strengthened my case to refer to the work and views of Walter Heape, Professors E. W. MacBride, A. Dendy, and M. Hartog—to mention only those Imown to me from old association—as confirming my earlier conclusions. I realize this after the event more fully than before, when I had in mind others who from their position and reputation have, rightly or wrongly, been regarded popularly as yet more leading representatives of British biology. Nor had I in mind American biologists. To have referred to them would have necessitated entrance at length into the Mendelian controversy, for all the morphologists in the States, I am inclined to think, are at the present moment keenly engaged over this matter. Possibly in the future, I shall have a word to say upon the important studies of Castle, Osborne, Whitman, Morgan, Jennings, and others, and the interpretation of the same in the terms of the biophoric concept. In the meantime may I assure my American confréres that I cannot call to mind one of them whom I would accuse of being “academic.” On the contrary, never has there been a period when American biologists have manifested so great an individual independence, so notable a diversity of opinion, so pronounced a desire to arrive individu- ally at the truth, irrespective of the schools and their teachings. The time indeed has passed when any biologist should justly be labelled as either a Lamarckian or a Darwinian. With abundant material presented to him and freedom of individual judgment, it is scarce possible that the student of to-day should accept unreservedly the teaching of either Lamarck or Darwin. x THE STUDY OF EVOLUTION He who is concerned at arriving at the truth is impatient of such labels : it is the truth he seeks, not the confirmation of the views of any one predecessor, however great be the admiration for his work and however large the debt he owes to him. Yet as regards the ancient controversy, this perhaps should be said, that in so far as between Darwin and Lamarck the essence of the teaching of the latter is that variation is an active process, a reaction on the part of living matter to its environment, the conclusions reached in these pages undoubtedly favour the Lamarckian view. Nevertheless, to accept them does not mean that the principle of natural selection is thereby excluded, or that the two principles are mutually antagonistic, but only that the influence of external forces is the primary process in the produc- tion of variation, and that natural selection is secondary, culling out those grades and forms of variation which are least economical and represent the less perfect adaptation on the part of individuals to the conditions in which the family or species finds itself for the time being. Seen thus, evolution, whether what we regard as progressive or as regressive, is the outcome of an active process of continuous adjustment between organisms and their environment. The survival of the fittest, it will be seen, does not depend upon chance variation. A given environment leads to variation in a particular direction, provided that the change in sur- roundings is not so great as to be beyond the adaptive powers of the organism. Where “chance” enters is in the nature of the new environment to which the individual, and the race, may be exposed. To the extent that the individual is unable to control his surroundings, to that extent is the race exposed to chance. It does not appear to have been sufficiently realized hitherto that here essentially it is that chance is operative. Conjugation and amphimixzis, it is true, are a cause of individual variation, but from the point of view of the race are distinctly conservative processes, tending to maintain the mean. When the first of the series of Croonian Lectures was pub- PREFACE xl lished in the pages of the British Medical Journal, together with an abstract of the second, the biologist whose attitude with reference to adaptation was the origin of those Lectures, saw fit to criticize them more suo. That my readers, with the Lectures before them, may reach their own conclusions regarding the validity of the criticism, it has been deemed proper to publish the correspondence as an Appendix. It is my pleasant duty to acknowledge my indebtedness to Messrs. Macmillan & Co. for their permission to reprint here the greater portion of a chapter from an article published origin- ally in Sir T. Clifford Allbutt’s System of Medicine, and republished. subsequently in book form under the title Inflammation; to Messrs. Lea Brothers & Co. (now Messrs. Lea & Febiger) of Philadelphia, for permission similarly to publish an extract from an article on “Inheritance and Disease” contributed to Sir William Osler’s Modern Medicine, to the Harvey Society of New York, and the Editors of International Clinics, British Medical Journal, the Lancet, New York Medical Journal, Mon- treal Medical Journal and its successor the Journal of the Canadian Medical Association, the Journal of Pathology and Bacteriology, Medical Chronicle, and Clinical Journal, to reprint articles contributed to their pages. To my friend, Captain R. G. Mathews, C.A.M.C., I am indebted for kindly co-operation in the preparation of the illustrations. Lonpon, August 1917. CONTENTS PART I ADAPTATION AND DISEASE BEING THE CROONIAN LECTURES DELIVERED TO THE ROYAL COLLEGE OF PHYSICIANS, LONDON, JUNE 1917 CHAPTER I Tue BasaL PrRopLemM or EvoLurion CHAPTER II ADAPTATION IN THE BacTERIA AND THE EVOLUTION OF THE Inrectious Diseases CHAPTER III ADAPTATION IN THE BacTERIA (continued) CHAPTER IV ADAPTATION TO DISEASE-PRODUCING AGENCIES IN THE HIGHER ANIMALS . CHAPTER V Tom INHERITANCE oF ACQUIRED ConDITIONS IN THE HIGHER ANIMALS . ‘ xi PAGE 15 28 45 60 xiv THE STUDY OF EVOLUTION CHAPTER VI Tue Puysico-CaemicaL Basis or IMMUNITY AND OF EvoLurIon. THe BriopHoric CoNcEPT CHAPTER VII Review oF CERTAIN CONCLUSIONS RESULTING FROM THE Bio- PHORIC CONCEPT PART II HEREDITY AND ADAPTATION CHAPTER I ON THE VARIABILITY OF THE BacTERIA AND THE DEVELOP- MENT OF Raczs (1892) CHAPTER II On THEORIES OF INHERITANCE WITH SPECIAL REFERENCE TO THE INHERITANCE OF ACQUIRED ConDITIONS IN Man (1901) CHAPTER III ADAPTATION AND INFLAMMATION (1905) . CHAPTER IV THe MYELIns AND PotEentTiaAL FLUID CrystaLLINE Bopigs oF THE ORGANISM (1906) CHAPTER V Tue DoMINANCE or THE NuciEus (1906) CHAPTER VI Tue ReDUcTIo AD AzBsURDUM OF WHISMANNISM (1907) . PAGE 70 83 103 132 161 168 188 210 CONTENTS CHAPTER VII A Lecture on Lire (1909) . CHAPTER VIII On Hasirs, Symproms, anD Disease (1911) . CHAPTER IX PARENTERAL DicEsTION aND Immuniry (1914) PART III ON GROWTH AND OVERGROWTH CHAPTER I On GROWTH AND OVERGROWTH, AND ON THE RELATIONSHIP BETWEEN CELL DIFFERENTIATION AND PROLIFERATIVE Capacity (1900) CHAPTER II On THE CauUsATION OF CANCEROUS AND OTHER New Growras (1901) CHAPTER III On THE CLASSIFICATION oF TumouRS (1902) . CHAPTER IV Syncytioma (DEcrDuoMA) Matianom: 118 BEARING UPON THE EssentiaL Nature or Mauienancy (1902) CHAPTER V UNIPOTENTIALITY, PLURIPOTENTIALITY, AND TOTIPOTENTIALITY or CELLS: A Note UPON THE CLASSIFICATION oF TUMOURS (1907) xv PAGE 216 235 250 263 276 305 326 334 xvi THE STUDY OF EVOLUTION CHAPTER VI ON THE RELATIONSHIP BETWEEN TuMoURS PROPER (BLASTOMAS) anD Hyperpastosis (1913) APPENDIX I Tur ExprRIMENTAL Propuction oF SPECIFIC VARIATION IN TypHorp Baciuul, By F. B. Bowman, M.B. (Tor.), Masor, C.A.M.C. : ‘ APPENDIX II Sir E. Ray LANKESTER REBUKES RUDENESS: A CORRESPOND- ENCE IN THE Pages oF THE BriTisH MEDICAL JOURNAL . INDEX . PAGE 340 351 354 363 ILLUSTRATIONS PLATES PLATE ; TO FACE PAGE I. Fossil and recent blue-green Algae (after Walcott) 18 II. The Myelins: doubly refracting ae ae from the adrenal cortex and liver . : . 168 III. The Myelins: Myelin forms from a ; Ductile ss (after Lehmann) i 176 LV. The Myelins: Distortion of fluid ais and aberrant forms of myelin globules , ‘ . 186 V. Schema of the =e of fertilization of the ovum = Boveri) : . , . 192 VI. Schema of tissue relationships 312 VIL. Diagram of a lepidic and a hylic tissue 316 FIGURES IN THE TEXT FIG. PAGE 1. Diagram of chemical constitution of an amino-acid nucleus of a protein 75 2. Diagram of constitution of a protein ring 76 3. Diagram of the affinities of a compound of two carbon atoms (after Bayliss) ‘ 77 4, Diagram of cell to show nuclear skein with chromomeres . 78 5. Diagram of mode of as and aa of the saa aa molecule : ; 81 6. Diagrammatic representation of the nature of enzyme action 86 7. Diagram of simple dissociation of peptone molecule 87 8. Diagram of interaction of substratum and receptor through inter- : . . 87 mediation of enzyme xvii XViil THE STUDY OF EVOLUTION . Diagram of alteration in constitution of biophoric molecule . . Graphie formula of the Pyrimidine ring . Diagram of production of multiple side-chain elements . . Diagram of interchange of allelomorphic side-chains between biophores of paternal and maternal origin . The different forms of chromosomes in the human spermato- cyte (after Moore and Arnold) . Cells of the salivary gland to show production and discharge of “plasmosomes” (after Maximow) . Aberrant mitoses (after v. Hansemann and Pianese) . Diagram of constitution of protein ring . Diagram of relationship between nuclear biophores and cyto- plasmic proteins . Chromosomes, chromomeres and “ids” . . Diagrammatic representation of constitution of protein or peptone nucleus . Diagram of growth of biophoric molecule PAGE 228 PART I ADAPTATION AND DISEASE THE CONTRIBUTION OF MEDICAL RESEARCH TO THE STUDY OF EVOLUTION CHAPTER I INTRODUCTORY : THE BASAL PROBLEM OF EVOLUTION I wave selected this subject of Adaptation and Disease, not merely because of its importance to physicians, but also, and to an even greater extent, because of its broad biological signifi- cance. The time is ripe, and more than ripe, for attention to be directed to the bearing of the investigations of the bacterio- logist on the one hand, and of the student of immunity on the other, upon what are some of the most important problems of general biology. For some little time I have been impressed by the fact that the latter-day investigations in medical science are of the very highest significance to the general biologist,1 and that with singularly rare exceptions the professional biologist —be he zoologist or botanist—has been superbly indifferent to them and to their bearing upon the basal problems of heredity and variation, and this notwithstanding the fact that investiga- tions into heredity and variation are, and must always be, his greatest concern. For this indifference and neglect there are, or may be, several extenuating circumstances. We ourselves are largely to blame in that we are more concerned with the bearing of our results upon our own medical work than with their wider biological significance. This wider significance, if it is referred to at all, finds incidental note. The titles of our articles, that is, are not such as attract the attention of the biologist, nor do we publish in the journals to which he is addicted. Not to mention foreign publications, the Journal of Pathology and Bacterio- logy, the Journals of Experimental Medicine, of Hygiene, In- 1 Five years ago this was the subject of my opening address as President of theSBiological Section of the Royal Society of Canada. Trans. Roy. Soc. Canada, 3rd series, 1912, vol. vi. section 4, p. 1. 3 4 ADAPTATION AND DISEASE fectious Diseases, of Medical Research are as unknown territory to him as the Quarterly Journal of Microscopical Science, the Journal of Morphology, or the Proceedings of the Linnean Society are to us. We would sooner think of writing a letter to the Times than to that academic go-between of men of science, Nature. And then, again, just as, in the old unhappy far-off days, a Bart’s man disbelieved that any good surgery could come out of Thomas’s or George’s, and the Thomas’s or George’s surgeon returned the compliment; just as the British medical man disbelieved such articles as appeared in the American medical journals, or, to come nearer to our own times, just as the Germans of late years, with rare and distinguished excep- tions, regarded themselves as the sole recipients of pathological truth, treating British, French, and American pathologists in general as very Nazarenes, so, it has to be confessed, there is a tendency for the academic biologist to be indifferent to, if not actually to resent, and throw discredit upon the work of those who, not belonging to his particular class, are therefore to be regarded as of the nature of outsiders. This is not a revelation of the spirit of pure science, but a comforting demon- stration that men of science are, nevertheless, pure human beings. Underlying this spirit is a natural and in many respects wise caution in accepting the observations. of workers with whose quality and standing the individual is unfamiliar. But this hesitancy may be carried too far. If I speak with a little feeling, it is because I still cannot forget the reception accorded by zoological confréres to the — most original, and at the same time most sound physiologist of his period, my old teacher and friend Walter Gaskell, when he was led by his studies upon the functions of the nervous system—studies which have so profoundly influenced modern medicine—to trace the development of the same, and doing this, after long years of close study of its comparative morphology, to reach conclusions regarding the origin of the vertebrate which were not in harmony with the doctrines of descent then currently accepted. So far as I, an outsider, could determine, each link in the chain of Gaskell’s reasoning was supported by appeal to observed facts, and by microscopical studies of singular interest ; so far as I, a pathologist, could test his conclusions, WALTER GASKELL 5 I found that incidentally they explained, as no other or earlier work had explained, the inter-relationship between the sym- pathetic system and the endocrine system, between the pituitary, thyroid, adrenals, and genital organs. Nor, so far as I can weigh evidence, can I find that any essential link in the chain has been shown to be out of place. Yet the attitude of the morpho- logists as a body was that of the Levite of the parable. His brother physiologists could not take up the cudgels on Gaskell’s behalf : it was for the morphologists to determine the value of the morphological evidence upon which his conclusions were based, and the morphologists in general declined to notice it, but, as though they regarded it as presumptuous for him, a physiologist, to enter their territory, they passed by on the other side. And the years followed the years, and Gaskell died feeling sore that the most sustained piece of work of his life had been side-tracked by those whom it should most have interested. Do not misunderstand me, and think that I am making a specific attack upon zoologists and botanists. As I have pointed out, we of the medical profession are tarred with the same brush. All I would urge is that just as we who are most interested in the advance of medical science accept gladly the results and the discoveries of workers in all branches of science, applying them to the elucidation and treatment of disease, so, in return, when investigators into the problems of medicine make notable advances, these be accepted willingly and utilized by the workers in other branches. It is not a matter of what we owe to those other branches in the first place; that is freely admitted. The renascence of medicine in our generation is due to the labours of men like Ferdinand Kohn the botanist, Pasteur the physical chemist, and Metchnikoff the zoologist, but if the dwarf, perched on the shoulders of the giant,! sees further and sees more than does the giant, it is not well to neglect his observations on the ground that he is a dwarf. 1 As might be expected, this metaphor was not original with Burton in the Anatomy of Melancholy. I find that Firmin-Didot (Alde Manuce, Paris, 1875, p. 343) cites Haureau (Histoire de la philosophie scholastique, Paris, 1872) as deriving it, according to Joannes Sarisberiensis (Metalogicus, vol. iii. cap. 4) from Bernard of Chartres in the twelfth century. 6 ADAPTATION AND DISEASE Tur NaturRE oF VARIATION The supreme biological problem of our times has been that of the ways and means of evolution. The fact of evolution all thinking minds accept. But as to how evolution has been, and is being, brought about is a very different matter. There is still as much debate as there was in the year following the publication of the Origin of Species. Upon consideration it will be seen that the fight truly centres upon the cause or causes of variation—whether the tendency to vary is something inherent in living matter, numerous variations being produced through this inherent tendency, of which those that are best fitted for their environment alone survive and are perpetuated : or whether variation is primarily and essentially brought about by the influence of forces acting from without upon a relatively labile living matter; whether, that is, variation! 1s primarily inherent, proceeding from within, or primarily acquired, proceeding from without. This, I would emphasize, is the basal problem of evolution, but oddly enough it has been largely neglected, the fight through all the years waging around what, after all, is a secondary problem, that, namely, as to whether properties acquired by the parent are capable of being transmitted to and reproduced in the off- spring. Long years prior to Darwin, you will remember, Lamarck propounded that they were, as did Erasmus Darwin and Lord Monboddo; Darwin wanted to believe that this was possible, but could obtain no clear evidence, and brought in finally a verdict of “non proven.” Herbert Spencer made this trans- mission one of his “ principles of biology,” but Weismann violently opposed the doctrine, carrying with him the bulk of latter-day biologists, until to-day Bateson, replete with his studies upon Mendelian properties, reaches the antipodal sugges- tion that when a new property manifests itself in any individual of any species it is not new, not due to addition, but to subtrac- tion and loss of properties already possessed: there is nothing new under the sun, and, in his opinion, evolution—like the squid— progresses backwards ; what appears to be a new property is, on 1 By an oversight this was delivered as “ variability ” at the Royal College of Physicians and so printed in the pages of the British Medical Journal. Pace Sir Ray Lankester (for whose criticism consult the correspondence at the end of this volume), my meaning was as obvious as was the oversight. WILLIAM BATESON 7 the contrary, primaeval, is the epiphany of a property possessed by the forerunners of the species which all along has lain latent, present but unable to manifest itself in consequence of the co- existence of inhibitory factors. That I may not be thought to exaggerate or misstate, let me quote, in the first place, from his address on Heredity delivered to the International Medical Congress here in London in 1913: “ Perverse as such a suggestion may appear, I do not think we should close our minds to the possibility that these dominants arise by a process of loss of some inhibitory factor. . . . Let me call your attention also to the inference which this suggestion would have on the conception of evolution. We might extend the same reasoning to all cases of genetic evolution, and thus conceive all alike as due to loss of elements present in the original complex.” That clearly this was not a passing fancy is shown by the address delivered by him at Melbourne in the summer of 1914, as President of the British Association for the Advancement of Science. “We are even more sceptical,” said Mr. Bateson, “as to the validity of an appeal to changes in the conditions of life as direct causes of modification, upon which, latterly at all events, Darwin laid much emphasis, . . .” “ Abandoning the attempt to show that positive features can be added to the original stock (the italics are mine), we have further to confess that we cannot often actually prove variation by loss of factors to be a real phenomenon.” Nevertheless this must be so, and he quoted the case of the “‘ Coral King ” Primula given off from the “ Crimson King,” concluding that here “ the salmon (pigment) must have been concealed as a recessive from the first origin of the variety,” and continued: “ Variation both by loss of factors and fractionation of factors is a genuine phenomenon of contemporary nature. If we have to dispense, as seems likely, with any addition from without, we must begin seriously to consider whether the course of evolution can at all seriously be represented as an unpacking of an original complex which contains within itself the whole range of diversity which living things present.” And further : “ At first it may seem rank absurdity to suppose that the primordial form or forms of protoplasm could have contained 8 ADAPTATION AND DISEASE complexity enough to produce the divers types of life. But is it easier to imagine that these powers could have been con- veyed by extrinsic additions? Of what nature could these additions be 2? Additions of material cannot surely be in question ” (the italics are mine). . . . And he winds up: “In spite of seeming perversity, therefore, we have to admit that there is no evolutionary change which in the present state of our knowledge we can positively declare to be not due to loss.” Now Professor Bateson is scarce a believer in the multiple origin of animal and plant forms: we know, indeed, that years ago he traced man and all vertebrate forms from the inverte- brates through an out-of-the-way animal, Balanoglossus, and incidentally in his Melbourne address he mentions this solution of the problem only to reject it ; wherefore, pushed to its logical conclusion, the Batesonian doctrine means this, that the primal unit, or units, of protoplasm from which all living animal and plant forms have descended possessed within them in a latent form the “ Anlagen,” or, not to be beholden to our enemies, the originals, of every organ and distinctive portion of an organ or part, even down to the conformation and coloration of in- dividual hairs and scales, and feathers and leaves, and petals and stamens, of all the manifold forms of life subsequently derived therefrom: that which was to outward seeming the most simple form of life was, verily, in constitution the most marvellously complex—and that actually what we regard as the higher forms of life are the lower, owing their development not to progressive accretions of properties, but to the reverse, so that reversion, instead of being a degenerative manifestation, a loss of properties acquired by the species, is, on the contrary, a recovery of higher and completer powers. Did ever any exercise of mediaeval scholasticism lead to more perverse con- clusion? The truth seems to be that Professor Bateson and the Men- delians, so far as regards the problems of evolution, are working in a cul-de-sac. Valuable and fascinating as are their observa- tions for the establishment and amplification of the law dis- covered by Gregor Mendel of cross-breeding of members of a species, that law only deals with the interplay of allelomorphs, id est, with the combinations and permutations of what for WILLIAM BATESON 9 simplicity sake may be termed positive and negative unit pro- perties possessed by the species: it only establishes the extent of the variation possible within the boundary of the species, and granting the existence of a definite number of allelomorphs, the number of possible strains obtainable within the limits of the species. But here it stops—save that of late workers have recognized the possibilities of fractionation of allelomorphs, and so of increase in the number of permutations and combinations. Accepting Mendelian data (and let me say I accept them whole- heartedly), I fail to see how any amount of interplay between properties already possessed by the species will result in the production of individuals which are outside the species. At most we produce different strains which, by cross-fertilization with other strains, produce individuals reverting to the usual type or types. If you invest in a kaleidoscope at a toy-shop, with the mirrors set at an angle of 60°, no amount of rotation will produce other than a six-sided pattern, or increase the number of colours in the pieces comprising’ the pattern. Only from without can new elements of other colour be added, thereby producing patterns of a new order: only from without can the angle of the two mirrors be altered so as to produce, say, a four- or a twelve-sided pattern. The interplay of allelo- morphs is not evolution, nor is it capable of throwing light upon the progressive development of new species. When Professor Bateson, from the vantage ground of his studies of the last fifteen years or so, begins to lay down the law regarding evolution, I cannot but help being reminded of Bombus, the bumble-bee—I would not say “in vacuo bombinans,” for that was said of a zoological monstrosity, and Professor Bateson is no chimera,! but—blundering out of the fields and hedgerows into a greenhouse, and bumping its head noisily again and again against the glass because of its incapacity to drive into that head the fact that transparency and penetrability are not neces- sarily associated phenomena. Nor is he alone. It so happens that some eighteen months ago, at the request of a mutual friend, a Fellow of the Royal College of Physicians, I found myself drawn into a lively dis- cussion with the Nestor of British biologists. I had not sought 1 Rabelais, Pantagruel, bk. ii. cap. 7. I owe the reference to my friend Mr. Louis Taylor. 10 ADAPTATION AND DISEASE the fight, but, once in, confess that I enjoyed the oppor- tunity of measuring my lance against so doughty a knight. The discussion arose over’a statement by the Fellow in question that the biologists of to-day had much to learn by turning their attention to the results being gained in medical laboratories. And, sure enough, after protesting with not a little vigour that the boot was on the other foot—that we medical men in our ignorance of biological progress were rediscovering and regarding as our own what had been gained by zoologists and botanists a generation or so previously—Sir Ray Lankester proceeded to justify absolutely my friend’s original contention by urging that one fallacy in all Lamarckian doctrine? is that adopted by Herbert Spencer, namely, what he called “ direct adaptation.” There is really, he laid down, no such thing. The supposed mysterious, and as it were miraculous, property of direct adaptation is always due to survival by selection of organisms which varied in many directions—the production of corneous epithelium, of increased hairiness, etc., being favourable variations, which hence have become inherent in tissues of all animals.? 1 I confess that I do not like being dubbed a Lamarckian, and that because, as commonly accepted, Lamarckianism is supposed to deal purely with the direct acquirement of alteration in structure through use and environment, and Herbert Spencer, by using the term “direct equilibration,” is largely responsible for this vulgar error. The phenomena we pathologists deal with present modification of structure merely as a secondary change: our pheno- mena underlie structural alteration. But in justice to Lamarck it deserves note that he expressly lays down “‘ whatever the environment may do, it does not work any direct modification in the shape and organization of animals. But great alterations in the environment of animals lead to great alterations in their needs, and these alterations in their needs necessarily lead to others in their activities. Now if the needs become permanent, the animals then adopt new habits, which last as long as the needs that evoked them ’’—and it is the new habits, he points out, which induce the structural alteration. (I quote from Hugh Elliot’s excellent translation of the Philosophie zoologique—Lamarck, Zoological Philosophy, Macmillan, 1914, cap. 7.) Granting this, I hold that the physicochemical explanation which will be put forward in the course of these lectures is something more precise and more limited in its scope than the * habits ” of Lamarck. 2 As Sir Ray Lankester has accused me of garbling his statement (see Appendix II.), and has not seen fit to withdraw the charge, I have no hesitation in quoting his exact words: “‘ One fallacy in all Lamarckian doctrine is that adopted by H. Spencer, viz. what he called ‘direct adaptation.’ There is really no such thing. The supposed mysterious, as it were miraculous, property of direct adaptation is always due to survival by selection of organisms which varied in many directions—the production of corneous epithelium, of increased hairiness, etc., being favourable variations, and hence have become inherent in tissues of all animals. But no more!” RAY LANKESTER 11 Here then we see the two foremost British biologists of our day, the one in doubt whether change in environment can be a direct cause of modification, and, filled with these doubts, willing to accept as a postulate that positive features cannot be added to the original stock, whereby he is led to an utterly perverse hypothesis ; the other equally denying that there can be external influences of such a nature that specific variation— ae. variation in particular directions—may be induced, and taking the stand that variation is multitudinous, the favourable variation alone having the opportunity to be propagated and reproduced. Now if there be one fact that is constantly being impressed upon the student of immunity and the worker in pathogenic bacteriology, it is that “ direct adaptation ” (2.e. specific modifica- tion in response to a specific alteration in environment within limits which will presently be laid down) is one of the basal phenomena of living matter. Our studies make it impossible for us to be blind to the fact that environment is capable of exerting a profound influence upon living beings, bringing about modifications of function and even of structure in particular directions. But evidently our experience and the diverse obser- vations upon which that experience is based are unknown to the academic biologists, although some biologists are beginning to see light. Thus it delighted me to run across the following admission in a valuable work published within the last few weeks—Pro- fessor D’Arcy Thompson’s Growth and Form:* “So long and ‘so far as ‘ fortuitous variations’ and the ‘ survival of the fittest ’ remain engraved as fundamental and satisfactory hypotheses in the philosophy of biology, so long will these ‘ satisfactory and specious ’ causes tend to stay ‘ severe and diligent enquiry ’ to the great arrest and prejudice of future discovery.” With this strong opposition on the one hand, and encouragement on the other, it has seemed to me a useful task to bring together and marshal in order the data bearing upon these matters as they present themselves to us, workers in medical science. 1 Growth and Form, by D’Arcy W. Thompson, F.R.S., Camb. Univ. Press, 1917, p. 6. 12 ADAPTATION AND DISEASE Tue Metsop or ATTACK There are two ways by which problems of this nature are a priort most likely to be solved, namely, by experiments upon the very simplest and, again, upon the most complex forms of life. I see that Dr. Bayliss as a physiologist casts doubts upon the value of the former as compared with the latter,’ pointing out that their very simplicity is in the majority of cases a dis- advantage, and quoting Claude Bernard to the effect that the lower (unicellular) forms of life possess all the essential pro- perties which exist in the (multicellular) forms higher in the scale, but possess them in a confused state, distributed, as it were, throughout the organism. The one organic cell fulfils a variety of purposes which in the higher organisms are relegated to distinct groups of cells. While freely admitting this conten- tion as regards the study of function, it has to be pointed out that for problems of adaptation and heredity the unicellular organisms possess the supreme advantages of rapid reproduction, coupled in the very lowest forms (according to our present knowledge, or want of knowledge #) with a complete absence of the disturbing influence of sex and conjugation. There is, that is, a greater likelihood of obtaining results, and the experi- ment becomes simpler, where we can in the course of a few hours subject one hundred generations to a particular alteration of environment, than when weeks, months, or years elapse before one new generation shows itself. In the latter case, to obtain results, either the alteration of environment must be made intensive to a degree that is likely to interfere with various vital functions, or, exhibited in a less intensive form, must act over unduly long periods. I know that certain biologists are unwilling to regard the products of asexual binary division of the bacteria, or the torulae of yeast (the results of budding), as true generations, and deny the right to regard the individual bacillus as an individual. One very distinguished biologist went so far as to declare to me that a long cultivation of a bacterial growth is “ one continuous individual,” in other words, 1 W. M. Bayliss, Principles of Physiology, 1915, p. 291. * For myself, with sex so widespread an attribute of living beings, I confess that I am wholly prepared to find that the schizomycetes, or some of them, exhibit a sexual, or conjugation, phase. THE METHOD OF ATTACK 13 that not merely do all the millions of bacilli in a single colony, say of the Bacillus tuberculosis, constitute one individual, but that one individual Bacillus tuberculosis is spread all over the habitable world, and that tuberculosis and not the tubercle bacillus is the entity. This is an impossible position : it formu- lates that the “divisa” are “indivisum.” The very idea of individual connotes independent existence, or, if we take a wide survey and include forms like the compound myxomycetes, hydrozoa and polyzoa, potentially independent existence. When a bacillus grows and divides and each half floats away, there is no longer one individual, and whether, as among the bacteria, the division is binary, or, as in man, one of the many billions of cells that constitute the body undergoes a similar binary division, and one of the products floats away and becomes fertilized, in both cases we deal with the development of a new generation. By the same process of reasoning, basing our- selves upon the doctrine of the continuity of the germ plasm, we might with equal logic declare that all living beings constitute one continuous individual ! And as regards the advantage in researches upon the bacteria of being freed from the perturbing factor of sex, let me interject that starting with Weismann and his doctrine of amphimixis, but more particularly during the last fifteen years under the influence of the Mendelians with their studies upon cross-breeding, we have been inclined to lay far too much stress upon the part played by sexual conjugation in the production of variation. In nature, in general, the tendency, if not the function, of sexual conjugation is to preserve the mean, not to induce the extreme, is to perpetuate the species rather than favour the variety : sexual conjugation only preserves and intensifies a variation when circumstances favour the segregation of individuals of the two sexes each possessing the variation, or, I would add, when those circumstances actually lead to the appearance of the variation in more than one individual in a particular locality. Even if a property be dominant, with indiscriminate mating and without segregation, such new property is apt to show itself proportionately in fewer and fewer individuals in successive generations. In simpler language, turn a highly-bred mastiff or terrier or beadle loose in a canine population, and his de- scendants descend to plain “ yellow dog.” It follows, therefore, 14 ADAPTATION AND DISEASE that on the whole we are more likely to obtain results where this levelling action of conjugation is wanting. I propose, therefore, to take up first the evidence of adapta- tion as affecting the pathogenic bacteria, next, of adaptation as it affects man and the higher animals, and, lastly, to discuss the application of the data brought forward to our conception of disease and disease processes on the one hand, of the evolutionary process on the other. CHAPTER II ADAPTATION IN THE BACTERIA Tur EvoLution or THE Inrectious Diszaszs 1 It is absurd in these days to imagine that the infections have always been with us: absurd to expand the Batesonian hypo- thesis and imagine that when the woman gave the man the fruit of the tree—or whenever man became man—with that most becoming knowledge of his nakedness he acquired the germs of all bodily ills: that while lues may already have in- fected his ancestors and their relatives the higher apes, the germs of typhoid, cholera, gonorrhoea, and other purely human ailments were already there, only waiting for his appearance to enter into his body, as into a house newly swept and garnished. Ture ANTIQUITY OF ZyMOTIC DISEASES Admittedly some diseases have been with us from the remotest historical times, aye, and we have evidence, from prehistoric times. The earliest Greek medical writings afford us an un- mistakable picture of tuberculosis. If we may accept Bishop Ussher’s chronology, the fifth and sixth chapters of the First Book of Samuel show—as I believe I was the first to point out, in the light of our modern knowledge of the natural history of this disease 2— that the Oriental plague was active over three thousand years ago, presenting the same striking characters as it manifests to-day. At a still earlier historical era, in fact in the earliest 1 This chapter follows the lines (though with considerable modification) of an address given by me before the Medical Society of the State of Vermont at its annual meeting at Rutland, Vt., in Feb. 1915, and published in the 1914 volume of the Transactions of that Society. 2 Montreal Medical Journal, xxiv., 1896, 995. 15 16 ADAPTATION AND DISEASE of all known writings, namely in the Ebers papyrus, descrip- tions are given of leprosy, and the Ebers papyrus is said to be of the twelfth dynasty, so that leprosy has been known for some four thousand years. It is through my old friend, Sir Armand Ruffer, whose recent death we deplore, a man who accomplished much for Egypt, and through his studies in what he described as palaeopathology, that we owe the knowledge of prehistoric disease in man. Mummies of yet earlier dynasties—and pre-dynastic—said to date back as far as four thousand years B.c. or six thousand years ago, demonstrate the most respectable antiquity of Bilharziosis, not to mention such everyday disturbances as Rheumatoid Arthritis and Pyorrhoea alveolaris. The characteristic eggs of Bilharzia are still distinguishable in the dried-up tissues of pre-dynastic mummies, so that anaemia and haematuria con- stituted a plague of Egypt before the Pharaohs as they do to-day when the Sultans and their suzerainty have passed away.) Tuberculosis, too, was there already. He demonstrated the bacilli in tissues in mummies from the Herst collection at Cairo belonging to the twentieth dynasty or so. Diseases which are not peculiar to man have indeed been diagnosed in fossil remains. Thus, according to Moodie,? caries has been noted in Permian fishes, pyorrhoea in the jaw-bone of an early tertiary three-toed horse, and arthritis and osteomye- litis in the remains of cave bears. THe ANTIQUITY OF THE BACTERIA This, after all, is only what might be expected : these lower forms of life preceded mammals and man, and bacteria must have been among the very early forms of particulate life. So 1 Just as the earliest known written document is medical, so my late col- league in Anatomy at McGill University, who, while this is passing through the press, from being Director of Recruiting and Brigadier-General has become Minister of National Service and Sir Auckland Geddes, has impressed upon me that the earliest known human fossil is pathological, pointing out that the remarkable thickness of the Piltdown skull, coupled with the characteristic outline of the temporal ridge, can only find their explanation by a diagnosis of Acromegaly, and suggesting that it is thanks to this disease and its results that we owe the survival of these remains through the ages. We do not, however, claim Acromegaly as a result of zymotic disease. 2 Trans. Chicago Pathological Society, x., 1916, 84. ANTIQUITY OF THE BACTERIA 17 long ago as 1879, Van Tieghem called attention to the evidence of bacterial existence, if not the actual presence of bacteria, in the silicified vegetable remains from the coal measures of St. Etienne. Since then, in a series of admirable memoirs, Renault 1 has confirmed and extended those observations. That marine Algae play an important part in certain geological horizons, notably in connexion with oolitic and dolomite structures, was laid down by Professor Garwood 2 in 1913. But even before this date a brilliant investigator, Drew, who died all too young, had in 1911 studied the calcareous muds now being deposited in the lagoons on the coast of Florida, and had shown that in the warm tropical waters of the Gulf the commonest living form is a denitrifying bacillus which, by the removal of the nitrogen from the water, leads to a combina- tion between calcium and dissolved carbon dioxide, with, as result, the precipitation of the insoluble calcium carbonate. He isolated and cultivated this form and obtained in witro the deposit of calcium carbonate from the sea water. In the follow- ing year he found the same Bacterium calcis extraordinarily abundant in the chalky mud of the Great Bahama reef, as many as 160 million bacilli being present in 1 c.cm. of the surface ooze.® These observations indicate, therefore, that bacteria, even to a greater extent than the larger marine Algae, have been responsible for the deposit of the vast beds of chalk and lime- stone in which no coralline or other fossils are to be detected. And now, in the oldest of all stratified rocks, in the pre-Cambrian or Algonkian deposits of America, Dr. Walcott, the head of the Smithsonian Institute, has discovered fossilized chains and clusters of cells which from their appearance and his description belong to the Cyanophyceae, the blue-green Algae closely related to the bacteria, and with these other clusters of coccus-like cells which may, or may not, be bacteria.* He likewise concludes that “it is quite probable that the bacteria were the most important factor in the deposition of ' Renault, B., “‘ Sur quelques micro-organismes des combustibles fossiles,”’ Bull. de la Société de V Industrie minérale, St-Etienne, vols. vii. and xiv., 1899, 1900 (with folio atlas of 20 plates of untouched photographs). 2 Geological Magazine, x., 1913, pp. 440, 490, and 545. 3 Papers from Tortugas Laboratory, Carnegie Institute of Washington, v., 1914, 44, 4 If bacteria then they are much larger than the micrococci of to-day. C0) 18 ADAPTATION AND DISEASE the Algonkian limestones,” 1 and that thus bacteria are to be regarded as largely responsible for the oldest of all known sedi- mentary rocks. Tue GroLocicaL PARALLEL Bacteria have been there, almost ab initio, but this does not, therefore, mean that all orders of pathogenic bacteria have always been with us, or that while certain infections are of an eminently respectable antiquity, this is necessarily true of all zymotic disease. Recognizing the unity of natural phenomena we must, I take it, hold that zymotic phenomena run parallel with geological. I mean this, that certain species, and indeed certain genera, have existed unchanged through countless ages to the present day. To-day we find the brachiopod Lingula living buried in the sand between the tide marks in the Tropics : we find identical fossil remains in the Cambrian rocks, usually (though wrongly) described as the earliest geological formations in which fossil remains have surely been discovered. As I have just pointed out, algae and bacteria are now known to antedate them by a long period. Here, then, is an animal which has per- sisted unchanged, over countless millions of years. The pearly Nautilus, with its exquisitely chambered shell, is still found in certain bays in the south-west Pacific: as Sir Archibald Geikie declared: “‘ This is a genus which has persisted through the greater part of geological time,” for identical chambered shells are found as fossils reaching back to the Silurian epoch. Limulus, the King crab, which is no crab but an arthropod, regarded by Gaskell as in the line of ancestry of the vertebrates and of man, is closely related to the Devonian Eurypterids, the fossil remains of that period differing in but secondary characters from the shells of Limulus of to-day. And so it is with shrimps like Anaspides? and yet other crustaceans, and with fishes such as Ceratodus, the King fish of Australia, which have remained apparently unaltered over extraordinarily long periods of geological time. But while this is so, we know equally well that during the same period other 1 Walcott, C. D., “Precambrian Algonkian Algal Flora,” Smithsonian Miscellaneous Collections, vol. \xiv. No. 2, 1914. 2 Towe these latter examples to my colleague at McGill University, Professor A. Willey, F.R.S. PLATE I oS osm? iS SS Fe ty anes S Yo000 FossIL BLUE-GREEN ALGAE (Walcott). A. Camasia spongiosa x 350.