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ON HEREDITY IN RELATION 
 TO DISEASE 
 
 THE HARVEIAN ORATION FOR 1908 
 
 Delivered before the Royal College of Physicians 
 OF London on October 19th, 1908 
 
 BY 
 
 J. A. ORMEROD, M.D., F.R.C.P. 
 
 ASSISTANT REGISTRAR TO THE COLLEGE ; 
 
 PHYSICIAN TO ST. BARTHOLOMEW'S HOSPITAL, AND TO THE 
 
 NATIONAL HOSPITAL FOR THE PARALYSED AND EPILEPTIC, 
 
 QUEEN SQUARE ; FORMERLY FELLOW OF JESUS 
 
 COLLEGE, OXFORD 
 
 ADLARD AND SON 
 
 BARTHOLOMEW CLOSE 
 1908 
 
K- K O li> i> 
 07 
 
 TO 
 
 SIE EICHAED DOUGLAS POWELL, BAET., 
 M.D., K.C.Y.O., 
 
 PRESIDENT OF THE ROYAL COLLEGE OF PHYSICIANS OF LONDON, 
 
 THIS ORATION, 
 
 DELIVERED AT HIS REQUEST, 
 
 IS DEDICATED 
 WITH SINCERE RESPECT AND ESTEEM 
 
 r^rufl 
 
THE HARVEIAN ORATION 
 
 OX 
 
 HEREDITY IN RELATION TO 
 DISEASE 
 
 Me. President, Fellows oe the College, 
 AND Gentlemen, — My first duty is to thank 
 yon, wliicli I do most sincerely, for entrust- 
 ing to me the vei^y honourable, though very 
 arduous, duty of delivering the Harveian 
 Oration this year. Such an honour must 
 bring to the mind of any man — it certainly 
 did to mine — first a feeling of pleasure and 
 of pride, which I hope may be pardoned, and 
 next a feeling of much anxiety and mis- 
 giving as to one's qualification for the task. 
 For it is indeed a serious thouo-ht that ever 
 since 1656, with but few intervals, this 
 
6 ON HEREDITY IN RELATION TO DISEASE 
 
 oration has been delivered by a long line of 
 distingnislied physicians, who have vied with 
 one another in holding np to admiration the 
 life and work of the illustrious man wdiom 
 w^e commemorate to-day. Certainly, had it 
 been possible, I should have wished to bring 
 before jou fresh facts about Harvey, or to 
 present some fresh aspect of his genius or 
 his character. But that I cannot hope to do. 
 For have we not already excellent lives of 
 Harvey, two of them, at least, recently 
 written, the work of skilful and sympathetic 
 historians like Dr. Norman Moore and Mr. 
 D'Arcy Power? And have not Harveian 
 orators within our recollection elucidated 
 fully the leading points and bearings of 
 Harvey's work ? Dr. George Johnson vin- 
 dicated the originality of his great discovery ; 
 Sir Edw'ard Sieveking brought before the 
 CoUeofe his re-discovered Lumleian lecture 
 notes ; Sir William Church has traced, from 
 Harvey as its source, the rise of physiology 
 in England ; Dr. Payne has shown us the 
 influence of Galen upon Harvey ; Dr. Norman 
 Moore and Professor Osier have drawn for 
 
ON HEREDITY IN RELATION TO DISEASE 7 
 
 US brilliant word pictures of tlie man, liis 
 times, liis friends, and his lectures at tins 
 College. Alas, that I cannot compete with 
 them ! that I have no fresh offering to 
 lay on Harvey's shrine ! and that I can only 
 bow my head, as do we all, in memorj^ of 
 this great and good man, of his noble char- 
 acter, his transcendent genius, and his im- 
 mortal discoveries. 
 
 But there are certain definite wishes ex- 
 pressed by Harvey about this oration. One 
 is that there be '' an exhortation to the 
 Fellows and Members to search and study 
 out the secrets of Nature by way of experi- 
 ment." Now, as to experiment in the limited 
 sense of physiological experiment, may we 
 not say that this wish has attained its con- 
 summation ? No reasonable medical man, 
 certainly no Fellow or member of our College, 
 would deny the greatness of the debt which 
 medicine owes to experimental science. How 
 far would the science and art of medicine have 
 progressed without a knowledge of the circu- 
 lation? — a knowledge which was obtained, as 
 Harvey himself tells us, by experiment, by the 
 
8 ON HEREDITY IN DELATION TO DISEASE 
 
 vivisection of many animals. The inter- 
 dependence of modern medicine and experi- 
 mental science was shown by your orator of 
 last year, Dr. Frederick Taylor, so fully that 
 I need not tread that ground again. It 
 is true that we cannot all be experimentalists 
 either in physiology or in other branches 
 of science. But there is no need to place 
 that narrow limit on Harvey's words. Cer- 
 tainly he speaks to each and all of us ; but 
 I think he means to emphasise herg, as he 
 so often does elsewhere, the importance of 
 independent individual research, whether by 
 experiment or observation, as opposed to a 
 blind or lazy submission to current theory 
 and authority. Knowledge of other men's 
 opinions he certainly did not under-rate, for 
 he was himself a most learned man ; but he 
 refused to let learning trammel investigation, 
 and would not look at Nature through the 
 distorting medium of a theory. And this 
 frame of mind is as valuable now as then, and 
 necessary, above all things, in the study of 
 medicine, for of many medical theories one is 
 tempted to say : 
 
ox HEREDITY IN RELATION TO DISEASE 9 
 
 " Our little systems liave tlieir clay ; 
 They have their day and cease to be." 
 
 Another wisli of Harvey's is tliat there 
 should be " a commemoration of all the bene- 
 factors ol the College by name," ''with an 
 exhortation to others to imitate these bene- 
 factors." As a benefactor who has not yet 
 been mentioned in an Harveian oration, I ask 
 yon to honour to-day Dr. Charles Coats, a 
 senior Fellow of our College, who has given 
 a sum of £1000 towards providing some 
 hospitable entertainment for our Members 
 and Licentiates ; this idea, suggested as I 
 believe, Sir, by yourself, took a tangible 
 form in the successful conversazione of last 
 summer. Such hospitality is entirely con- 
 sonant with Harvey's spirit, and that enter- 
 tainment of the Members and Licentiates 
 was the proper complement of the " General 
 Feast" which he instituted for the Fellows 
 to-day. 
 
 Xow the names of those benefactors who 
 have founded lectures, scholarships and prizes 
 are recorded with all due particulars in the 
 Annual List of the College, and are so well 
 
10 ON HEREDITY IN RELATION TO DISEASE 
 
 known to you that I need not recapitulate 
 them. But besides these, and others than 
 these, who have given money, lands, hooks 
 or other good things to the College, there 
 are those who have devoted their time and 
 talents to its service, or who have shed a 
 lustre upon it by their learning, their 
 discoveries, or their distinguished career. 
 They, also, in the truest sense are benefactors 
 of the Colleo^e. I look in that invaluable 
 
 o 
 
 book. Dr. Munk's 'Roll of the College of 
 Physicians,' and I see — first, a long list of 
 Presidents under whose care and devotion 
 the College has thriven, reaching back from 
 yourself, Sir, to our revered founder Linacre; 
 next, men famous in science, physicists like 
 Grilbert, WoUaston, Thomas Young, Arnott; 
 chemists, such as Prout and Alexander 
 Marcet; naturalists and botanists, such as 
 Fothergill, William Pit cairn. Sir Hans 
 Sloane; anatomists and physiologists, at 
 whose head stands Harvey himself, Richard 
 Lower, and such great names as those of 
 Glisson, Havers, William Hunter, Wharton, 
 AYillis. There have been famous authors 
 
ON HEREDITY IN RELATION TO DISEASE 11 
 
 and men of letters — Sir Thomas Browne, the 
 anniversary of whose birth and death is 
 to-day, Akenside, Arbuthnot, Grarth, and 
 (strange contrast) Stnkeley the antiquarian, 
 and many others well known for scholarship, 
 learning and literary talent. There are the 
 great masters and discoverers in medicine^ 
 such as Sydenham, Matthew Baillie, Bright, 
 Addison. And some have been also known 
 for their simplicity of character, their high 
 ideals, and their life of transparent goodness. 
 Such I think must have been David Pitcairn, 
 of whom Dr. Munk says that he was 
 simple, gentle, dignified, and ver}^ kind of 
 heart ; and such William Babington, of whom 
 the same authority says, " History does not 
 supply us with a physician more loved or 
 more respected," and such a one was Peter 
 Mere Latham — scholar, physician, inspiring 
 teacher, eloquent writer, high-toned gentle- 
 man, devout Christian. 
 
 I know that one of our Fellows, whose 
 untimely death we all deplore, took Dr. 
 Latham, though he never saw him, for his 
 model and example. 
 
12 ON" HEREDITY IN RELATION TO DISEASE 
 
 These are Ijiit a few of the many noble 
 figures which fill the great jDageant of our 
 past ; but need I, Sir, say more ? For I am 
 sure that Fellows of the College know so 
 well the lives and works of our illustrious 
 predecessors that for an " exhortation to 
 imitate them " it will suffice to have recalled 
 their names. 
 
 Many of my predecessors in this office 
 have varied the theme of their Harveian 
 oration by introducing into it some subject 
 of general medical interest, and I ask your 
 leave, Mr. President, to follow their example. 
 I desire to direct attention to the great 
 subject of heredity, and in particular, here- 
 dity in disease. A distinguished German 
 physician has said, " There are no inherited 
 diseases."* We need not argue that, for we 
 should all admit that heredity has much to 
 do with the production of disease. Nov/ of 
 that mysterious thing inheritance I need only 
 say that it lies at the very root of our being 
 both as individuals and as a race, as, indeed, 
 
 * Martins, ' Kranlclieits-anlage iind Yererbung,' p. 14, 
 (Leipzig and Wien, 1905). 
 
ox HEREDITY IN RELATION TO DISEASE 13 
 
 is recognised in the proverbs and tlie religions 
 of all nations. '' Fortes creantnr fortibns," 
 said Horace. " The fathers have eaten 
 sonr grapes and the children's teeth are set 
 on edge." The Chinese worship their an- 
 cestors ; and there are words familiar to 
 onrselves concerning a visitation " nnto the 
 third and fourth generation." 
 
 This year, too (1908), is the fiftieth anni- 
 versary of the paper written by Charles 
 Darwin and Alfred Wallace " On the Ten- 
 dency of Species to form Varieties, and on 
 the Perpetuation of Varieties and Species by 
 Natural Means of Selection,"* which consti- 
 tuted the inception of that theory of evolu- 
 tion which has since dominated scientific 
 thought, and which has for its basis the facts 
 of inheritance. 
 
 But granting the importance of the subject, 
 what has it to do with Harvey ? jN^ot much, 
 perhaps, if we limit our thoughts to his great 
 and enduring work on the circulation of the 
 blood. But we know that other problems in 
 
 * Read before tlie Linnteaii Society of London, Jidj 1st, 
 1858 {vide ' Times/ June oOth and July 1st, 1908). 
 
14 ox HEREDITY FN EELATION TO DISEASE 
 
 physiology occupied liis mind. It is true 
 that it was hxte in Harvey's life when his 
 friend Dr. Ent obtained from him for publica- 
 tion his book ' De Generatione Animalium/ 
 and almost ao^ainst his will, for he knew that 
 it was incomplete. Yet it seems that he had 
 been patiently collecting facts for it many 
 years before, and one whole section of it, on 
 the generation of insects, had been destroyed 
 by his political enemies as ruthlessly as they 
 mio'lit have wrecked a cathedral. One is 
 
 o 
 
 tempted looking on his two great works to 
 contrast them by saying, that the ' De Motu 
 Cordis et Sanguinis ' arose complete, conclu- 
 sive, victorious, like Pallas from the head of 
 Zeus, while in the ' De Generatione ' we 
 witness his painful and laborious searcliings 
 after truth. But that would be a superficial 
 contrast, for we know that the truth con- 
 cerninsf the circulation was incubatino- in his 
 mind for some ten j^ears before it found final 
 expression, and we have been taught by the 
 Harveian orator of two j^ears ago that the 
 growth of truth is sIoav. Granted that in the 
 ' De Generatione ' he did not attain to the 
 
ox HEREDITY IX RELATION TO DISEASE 15 
 
 full knowledge wliicli he desired (tliat, indeed, 
 was impossible witli tlie meagre means of 
 observation at liis command), yet we cannot 
 bnt admire his method in the collection and 
 presentation of facts within his reach. I 
 imagine that no better acconnt of the pheno- 
 mena of development conld have been given at 
 that date than Harvey gives in his chapters 
 " On the Inspection of the Egg," and " Of 
 the Order of the Parts in Generation as it 
 appears from Observation." It is only when 
 facts fail him that we fail to follow his con- 
 clnsions. To give an example : " It is cer- 
 tain," he says, " that no semen reaches the 
 nterns " — he had no microscope wherewith to 
 identify the spermatozoa — " therefore the 
 v,^oman becomes fecundated without the co- 
 operation of any corporeal agent, in the same 
 way as iron touched by the magnet is endowed 
 with its powers and can attract other iron to 
 itself."* A bold analogy indeed, drawn 
 from a branch of science which then was very 
 young; but it shoAvs, like many other ]Dassages 
 
 * ' Harvey's Works,' translated by Willis for the Sydenliam 
 Society, 1847, p. 575 (" On Conception "). 
 
16 ox HEREDITY IN RELATION TO DISEASE 
 
 from liis works, that Harvey, with all his zeal 
 and reverence for facts, had his gaze fixed on 
 the great mysteries of life ; on the marvel of 
 conception, on the efficient canse (to nse his 
 own phrase) of reproduction, and on heredity 
 in its widest sense. For does he not himself 
 say : "In truth there is no proposition more 
 mao'nificent or more useful to ascertain than 
 this : How are all things formed by an uni- 
 vocal agent ? How does like ever generate 
 the like ? And this not only in productions 
 of art (for so house builds house, face designs 
 face, and image forms image), but also in 
 thing relating to the mind ; for mind begets 
 mind, opinion is the source of opinion. Demo- 
 critus with his atoms, and Eudoxus with his 
 chief good, which he placed in pleasure, 
 impregnated Epicurus, the four elements of 
 Empedocles, Aristotle ; the doctrine of the 
 ancient Thebans, Pythagoras and Plato ; 
 geometry, Euclid. By this same law the 
 son is born like his parents, and virtues 
 which ennoble and vices which degrade a 
 race are sometimes passed on to descen- 
 dants through a long series of years. Some 
 
ox HEREDITY IN RELATION TO DISEASE 17 
 
 diseases propagate their kind, as lepra, gout, 
 syphilis and others. But why do I speak of 
 disease, when the moles, warts and cica- 
 trices of the progenitor are sometimes re- 
 peated in the descendant after many genera- 
 tions. Every fourth birth, says Pliny, the 
 mark of the origin of the Dacian family is 
 repeated on the arm." 
 
 "Why may not the thoughts, opinions and 
 manners now prevalent return again, after 
 an intermediate period of neglect ? For the 
 Divine mind of the Eternal Creator, which is 
 impressed on all things, creates the image of 
 itself in human conceptions."* 
 
 I quote these words of the great master 
 
 in the hope of persuading you that some 
 
 remarks on heredity may not, after all, be 
 
 alien to an Harveian oration ; and if I invite 
 
 your attention to that subject for the brief 
 
 time that remains, it is not, believe me, with 
 
 any vain-glorious expectation that I shall 
 
 add to your knowledge, either of facts or of 
 
 theory, but only that I may perchance — again 
 
 to cpiote the words of Harvey — " stir ujj the 
 
 * Ihid., p. 582. 
 
 o 
 
18 ON HEREDITr ]N RELATION TO DISEASE 
 
 intellects of the studious to search more 
 deeply into so obscure a subject." 
 
 It would be interesting, doubtless, to con- 
 sider what answers modern authors make to 
 the question over which Harvey puzzled, 
 namely. How comes it that the embryo is 
 laid down, with definite parts, in a definite 
 order, and so that it eventually resembles its 
 parent ? That would mean a consideration of 
 such theories as the pan-genesis of Charles 
 Darwin, the determinants of Weismann, and 
 the mneme or unconscious memory of Richard 
 Semon — a doctrine set forth, you will re- 
 member, by Francis Darwin in his Presiden- 
 tial Address to the British Association this 
 year. But these things I am not competent 
 to expound, neither would time permit me to 
 try. I will therefore only raise such points 
 as seem to have direct practical bearings 
 for us. 
 
 And first comes the old question, " Are 
 acquired characters transmissible ? " Have 
 those external forces and events, which help 
 to fashion our own life and being, any similar 
 effect, through ourselves, upon our unborn 
 
ON HEREDITY IN RELATION TO DISEASE 19 
 
 children ? I tliink tliat the plain, unlearned 
 man would certainly say " Yes," and so did 
 the learned till a short time ao-o. Lamarck's 
 views of natural history, and the theory of 
 natural selection as first propounded by 
 Darwin, assumed the possibility of such trans- 
 mission, and numerous illustrations of it as 
 regards man and his diseases were collected, 
 perhaps in an uncritical fashion, by Prosper 
 Lucas and others. But it is incompatible 
 with Weismann's theory of heredity, which is 
 now so widely held. The central idea of that 
 theory is the '' continuity of the germ-plasm." 
 By germ-plasm is meant the formative tissue, 
 out of which, or under the guidance of which, 
 each individual is fashioned. It matters little 
 to the theory whether this germinal plasm is 
 identified with the germinal cells (as for- 
 merly), or with the much minuter particles 
 of their nuclei known as " chromosomes." 
 The germ-plasm is continuous, that is to say, 
 it is not manufactured afresh within the indi- 
 viduals of each generation for the purpose 
 of procreating the next, but it is handed on 
 from generation to generation, only changing 
 
20 ox HEREDITY IN liELATION TO DISEASE 
 
 in this sense, that as each successive indi- 
 vidual is made a portion of the germ-plasm 
 is set aside within him whereby he will carry 
 on the work of generation when his elders 
 liave perished. So that we are not links in a 
 chain of life, but rather flowers or leaves 
 which spring from a common stem, the germ- 
 plasm. And in the same way I am not, 
 strictly speaking, my son's father, but his 
 elder brother (to be accurate I should say his 
 half-brother), nor am I my father's son, but 
 his yoimger brother ; the real father of us all 
 is the family germ- plasm, and my duty to 
 that father is to accommodate him in the 
 house he has built — my body — till he has 
 built himself a new one — my son's body. 
 The reason for the resemblance of successive 
 generations to each other is now obvious ; it 
 is because they are all brothers, made out of 
 the same stuff on the designs of the same 
 architect. It is ol^vious, too, that the effects 
 of external conditions on one generation will 
 not be reproduced in another, unless the 
 same external conditions happen to act again. 
 If a caterpillar has gnawed a hole in a leaf 
 
ON HEREDITY IN RELATION TO DISEASE 21 
 
 upon a tree, the otlier leaves will not have 
 holes in them unless the caterpillar has 
 gnawed them too. 
 
 Then, do the ills acquired by the parents 
 have no effect on the well-beino* of their 
 children ? Few people, surely, would main- 
 tain that. For the germinal plasm is lodged, 
 at any rate, in the parent's body ; if he dies, 
 it dies ; and if he suffers from any deeply 
 reaching disorder of nutrition, the probability 
 is that it must suffer too. And such nutri- 
 tional probabilities, I need hardly say, are 
 numerous. We need not suppose, then, that 
 exhausting diseases which may affect the 
 whole organism, such as alcoholism, diabetes, 
 syphilis or phthisis, are without effect upon 
 the health of our children. And is it not 
 also possible that similar far-reaching effects 
 may be produced by other influences not 
 strictly nutritional, say, for example, some 
 nervous shock ? May not a violent commo- 
 tion of the branches of the tree affect its 
 stem ? 
 
 Still, it is one question whether disease 
 acquired by a parent can produce ill effects 
 
22 ON HEREDITY IN RELATION TO DISEASE 
 
 on liis children of a general kind (a tliesis 
 which to my mind can hardly be denied) ; 
 it is another question whether, when a patient 
 has acquired a particular disease, disease of 
 the same or of a similar kind is likely to 
 occur in his children ? Those who deny this 
 absolutely say, first, that it never happens. 
 Observation must be the test of that. 
 Secondly, that it cannot happen, because it 
 is contrary to theory, and because we know 
 of no mechanism whereby the body-cells 
 could communicate their modifications to the 
 germ-plasm. But ought the door to be 
 slammed in the face of further inquiry ? Is 
 there not still here a legitimate field for 
 observation ? 
 
 At first sight there appears to be a glaring 
 instance of such transmission, that is, syphilis. 
 But this is dealt with as follows : Either 
 the child imbibes the virus in nfero by the 
 placenta from an infected mother — this is 
 evidently an antenatal infection rather than 
 inheritance ; or else the virus is introduced 
 by the sperm-cells of the father at the very 
 moment of conception — this again, whatever 
 
ON HEREDITY IN E ELATION TO DISEASE 23 
 
 it may appear to us, is to tlie biologist not 
 inheritance, but an infection of still earlier 
 date than the last. Similarly it is denied 
 that there can be a true inheritance of any 
 microbic disease whatever. Suppose we 
 assent to that, yet susceptibility to such 
 diseases, in either a plus or minus direction, 
 that is, proclivity to them or power of resist- 
 ance to them, may be inherited. And may 
 not such susceptibility be first acquired and 
 then transmitted? When measles appeared 
 in Fiji for the first time its ravages were far 
 more severe there than among ourselves, 
 with whom it has long been endemic. The 
 simplest explanation of this (I know there 
 are others) seems to me to be, that we have 
 acquired and then perpetuated some degree 
 of resistance to the disease. Suppose that a 
 man of healthy stock acquires phthisis, will 
 his cliildren be more prone to phthisis or no? 
 Our Treasurer, in his ' Treatise on Grout,'* 
 says " the fact of acquired gout must be 
 accepted." Suppose, then, a man of healthy 
 
 * ' A Treatise on Gout,' by Sir Dyce Duckworth, London, 
 1889, p. 129. 
 
24 ON HEREDITY iX KELATION TO DTSEASK 
 
 stock acquires gout, are his children likely 
 to be gouty? Suppose, again, that a man in 
 consequence of a blow on the head becomes, 
 like Brown- Sequard's guinea-pigs, epileptic, 
 is there any risk that his children will be 
 epileptic ? Suppose that a man has syphilis 
 in early life, and later on becomes a general 
 paralytic, ought we to feel more anxious 
 about the mental future of children begotten 
 during his last illness than about that of his 
 earlier ones ? 
 
 I confess for myself that I do not know 
 the answer to these questions, but I think 
 that there are those among my audience 
 whose experience could supply it, and who 
 are well qualified to " search and study out 
 this secret of Nature," whether acquired 
 diseases are in any degree transmissible to 
 our children or no. 
 
 I must now refer, though in the briefest 
 possible way, to the work of Mr. Francis 
 Gralton, Professor Karl Pearson, and those 
 others who have enriched the stud}^ of here- 
 dity by the method of statistics, if only to 
 express my admiration for their arduous 
 
ON HEREDITY IX EELATIOX TO DISEASE 25 
 
 labours. It may be that statistics do not 
 appeal so forcibly as tliey ought to do to tlie 
 medical man, because lie lias principally to 
 deal with indiyiduals. Xeither liaye statistical 
 methods, so far as I know, been largely 
 applied as yet to the subject of heredity in 
 disease. But neyertheless the general prin- 
 ciples eyolyed from them must haye their 
 application for us. Thus the "law of 
 ancestral inheritance " reminds us that we 
 are hybrids — mongrels in an extreme de- 
 gree — or to put it more pleasantly, that our 
 inheritance is yery composite, a patchwork 
 or mosaic pieced together from the characters, 
 first of our two parents, next of our four 
 grandparents, and then in a diminishing 
 ratio from an almost infinite number of 
 ancestors, wdio probably included all sorts 
 and conditions of men. Secondly, the "law 
 of filial reo-ression or correlation " declares 
 that although children resemble their parents 
 in the main, neyertheless, unless constant 
 attention be giyen to breeding, there is a 
 tendency among the descendants of any indi- 
 yidual parent to smooth out any striking 
 
26 ox HEREDITY IN KELATION TO DISEASE 
 
 peculiarities lie may have jDossessed and to 
 bring tliem, whether it be upwards or down- 
 wards, to the average level of his multitu- 
 dinous ancestry. So that the average man 
 cannot hope to escape mediocrity, unless, as 
 the saying goes, he has been very careful in 
 the choice of his ancestors. 
 
 But the mention of the word "hybrid" 
 naturally leads our thoughts to the discoveries 
 of Mendel. Now, were romance permissible 
 in an Harveian oration, it might well be 
 evoked by the story of Gregor Johann 
 Mendel, peasant-born, priest by vocation, yet 
 a student of science, and a man of rare scien- 
 tific insight; whose life was spent as priest 
 and as Abbot at the Monastery of Briinn, 
 and whose leisure was spent in the study of 
 hybridisation of plants. He died in 1884^ 
 unknown to scientific fame, and his work, 
 buried in the proceedings of a local scientific 
 society, was like to have died with him ; but 
 it has been disinterred in this century by 
 those who recognise in it the hand of genius, 
 and compare it in importance to the work of 
 a Newton or a Dalton. 
 
ox HEllEDLTY IN EELATION TO DISEASE 27 
 
 It is to Professor Bateson that vre in this 
 country are chiefly indebted for the exposi- 
 tion and ehiboration of Mendel's work. The 
 principles of Mendelism, as it is now called, 
 are admirably summarised in a little book by 
 Mr. Punnett.* I shall borrow from him and 
 not tax your patience long. 
 
 Mendel showed that in the study of inheri- 
 tance it was possible to select certain simple 
 characters whose nature was more or less 
 opposed, such as tallness and dwarfism, rough- 
 ness and smoothness, colour differences and 
 the like. These could be studied apart from 
 other characters, and were found by him to 
 behave in a definite way, as follows : Suppose 
 a plant which is of a pure tall breed is ferti- 
 lised from a similar breed, the resultant off- 
 spring is of course the same, viz. pure tall ; 
 and from a pure dwarf breed treated in the 
 same way the results are pure dwarfs. If a 
 pure tall, however, be fertilised from a pure 
 dwarf, the result must be a generation of 
 hybrids ; and one might expect them to be of 
 medium heio-ht. But this is not the case; 
 
 * ' Mendelism,' by R. C. Pimnett (Macmillan, 1907). 
 
28 ON HEREDITY JN RELATION TO DISEASE 
 
 they are all tall. It looks as if the tallness 
 had swamped the dwarfism ; so that we may 
 call the tallness a dominant character and 
 the dwarfism a recessive character. Bnt 
 though these hybrids are tall in appearance, 
 the dwarf element has not wholly disappeared, 
 it remains in respect of their powers of pro- 
 pagation. For if these tall hybrids be inter- 
 bred together the dwarfism comes out again 
 in their progeny ; so that in the third gene- 
 ration there are some tall, some dwarf. 
 Moreover, there is in this third generation 
 a definite proportion between the two 
 varieties, namely three tall to one dwarf ; or 
 to speak more accurately (as can be proved 
 by further interbreeding), one pure tall, two 
 hybrids which appear tall, and one pure 
 dwarf. The theoretical interpretation of 
 these facts is that the pairs of characters 
 which behave in this way (allelo-morphic 
 pairs as they are termed) do not blend in the 
 germ-cells or gametes, but that each gamete 
 carries either one of the characters or the 
 other; and further, that the difference between 
 a pure breed and a half-breed is this, that in 
 
ON HEREDITY IN RELATION TO DISEASE 29 
 
 a pure breed all the gametes carry one of the 
 characters, to the complete exclusion of the 
 other, while in a half-breed half the gametes 
 carry one character and half carry the 
 other. 
 
 Mendel made his classical experiments on 
 plants ; they have been repeated by other 
 observers, not only with plants, but with many 
 forms of animals, e. g. insects, snails, poultry, 
 pigeons, rats, mice, rabbits ; and many 
 characters have been studied from this point 
 of view. One result may be quoted as specially 
 interesting to physicians. It is that when a 
 certain species of wheat which is very sus- 
 ceptible to the ravages of a fungus which 
 causes "rust," is crossed with another species 
 which is not susceptible, the immunity to 
 rust which reappears in the resulting strains 
 of wheat distributes itself in the Mendelian 
 proportion. This suggests the possibility 
 that something of the same sort may hold 
 with respect to our own susceptibilities to 
 disease, and raises the very questions which 
 interest us most. For we want to know 
 whether Mendelian laws are applicable to 
 
30 ox HEREDITY IX RELATIOX TO DISEASE 
 
 man, to his normal characteristics and to 
 conditions of disease, and how far they are 
 applicable. 
 
 This question cannot be answered com- 
 pletely. Observations have been made (many 
 of them, I imagine, under the inspiration of 
 Professor Bateson) on various points, such as 
 the colour of the iris by Mr. Hurst; here- 
 ditary diseases of the eye, such as cono-enital 
 cataract, night-blindness, and colour-blind- 
 ness by Mr. Nettleship ; haemophilia, albinism, 
 alkaptonuria by Dr. Garrod ; hereditary de- 
 formities of the limbs by Farabee and others.* 
 Dr. Gossage has rightly drawn attention to 
 the importance of hereditary diseases of the 
 skin, which are easily observed, and has 
 himself investigated the condition known as 
 tylosis of the hands and feet.f It would 
 appear that in some cases the Mendelian 
 proportion works out — in enough, perhaps, to 
 encourage further research ; but I do not 
 know whether more can be definitely said. 
 The difficulties are sufficiently obvious. The- 
 
 * Vide Professor Bateson's Address to the Neurological 
 Society, ' Brain,' vol. xxix, p. 157. 
 
 f ' Quarterly Journal of Medicine," vol. i, No. 3, p. 331. 
 
ON HEEEDITY IN RELATION TO DISEASE 31 
 
 only metliocl of inquiry at present open seems 
 to be the patient collection of pedigrees ; 
 experiment is possible with plants and 
 animals, but not with mankind. We cannot 
 pick parents to breed from. The pedigrees, 
 too, must be complete, not only as to the 
 number of diseased people, but also as to the 
 number of the normals, since the proportion 
 between tlie two is a vital point. A pedigree 
 should embrace at least three generations, 
 therefore the facts can rarely be the result 
 of the physician's direct observation. Again, 
 the numbers in human families are at best so 
 small that a single vitiating instance may 
 make a large error in the proportion of 
 normals to abnormals; and it is difficult to 
 know what to do with still-births, children 
 who die young, or others of whose condition 
 nothing may be known. This numerical 
 difficulty may be partially met by adding up 
 the totals of many families, but that is 
 certainly a method to be employed with 
 caution. And this, too, has to be remembered, 
 that certain modifications have been intro- 
 duced into the original Mendelian laws which 
 
32 ox HEREDITY IX EELATIOX TO DISEASE 
 
 are, no doubt, necessary and correct, but 
 wliicli tend to mask their simplicity of appli- 
 cation. Such, for instance, is the interaction 
 of tAvo sets of characters, whereby the 
 dominance of one member of an allelo- 
 morphic pair over the other is rendered 
 conditional on the presence of a third 
 character. Thus it has been supposed, on 
 the analogy of other facts, that haemophilia 
 is a character which becomes dominant or 
 recessive according as the sex of tlie person 
 is male or female, and that this accounts for 
 the rarity of female bleeders. Such modifi- 
 cations and complications may make the 
 interpretation of a pedigree as difficult as its 
 construction ; and it may be necessary to 
 refer it for its interpretation to someone who 
 knows the business well. 
 
 In some diseases, where family pedigrees 
 are not easily obtainable, all that we can say 
 is that the facts agree with some side deduc- 
 tion from Mendel's theorj^ It appears that 
 first-cousin marriao^es form one of the causes 
 of alkaptonuria, and it is pointed out that 
 this is just what Avould happen if alkap- 
 
ON HEREDITY IN RELATION TO DISEASE 33 
 
 tonuria were a rare recessive character in the 
 Mendehan sense. The character, being re- 
 cessive, would not appear on the surface 
 until two similar hybrids — hybrids, that is, 
 possessing the character — intermarried. And 
 since the character is rare, two such hybrids 
 are not likely to meet unless they are of the 
 same family. And that is one thing that may 
 be said, on Mendelian principles, about con- 
 sanguineous marriages in general. They are 
 a means of bringing to light hidden (reces- 
 sive) characters. Such characters may be 
 ofood or bad : we cannot tell beforehand. So 
 that the State of Wyoming, which Lord 
 Rosebery tells us* has forbidden first-cousin 
 marriages, may have prevented evil or may 
 have stifled good. 
 
 The study of heredity in disease is likely 
 to be particularly interesting in the sphere of 
 the nervous system. For in the first place 
 heredity is here an agent of great power; it 
 ranks with injuries, infections and intoxica- 
 tions as one of the principal causes of chronic 
 nervous degeneration. Again, in proportion 
 
 * ' Times,' July 1st, 1908. 
 
 a 
 
84 ON HEREDITY IN RELATION TO DISEx\SE 
 
 as our civilisation becomes more and more 
 elaborate, so Ave depend for progress more 
 and more upon our nervous system, upon its 
 flexibility and capacity for adjusting itself to 
 the complication of our surroundings. This 
 suggests the possibility that the ways in 
 which heredity moulds this plastic material 
 may be varied ; that just as a young and grow- 
 ing comnnmity has to feel its way towards 
 the establishment of its laws or its jDolitical 
 system, so here, perhaps, those sequences 
 which we call laws of heredity may not yet 
 have attained a rigid uniformity. How^ever 
 this may be, there are at least two ways in 
 which heredity manifests itself in diseases of 
 the nervous system. The first relates to 
 that common group of maladies known as 
 neuroses. This group includes such affections 
 as epilepsy, insanity, hysteria, neurasthenia, 
 tics, alcoholism, etc., which are characterised, 
 so far as we know them at present, by 
 perverted nervous action rather than by 
 coarse structural disease. They are related 
 together in this way, that they seem to be the 
 expressions, varied and inter - changeable 
 
ON HEEEDITY IN RELATION TO DISEASE 35 
 
 inter se, of someone underlyingnervous defect; 
 we may perliaps call them tlie ill-timed or 
 inappropriate response of a nervous system 
 Avliicli adapts itself badly to its surroundings. 
 This deeply-seated nervous defect, whatever 
 its precise nature may be, is hereditary in a 
 high degree, so that the "neuropathic family" 
 is now notorious in medicine. One member 
 of it may be epileptic, another insane, another 
 eccentric and so forth, but the faulty nervous 
 constitution is the same in all. So much we 
 know, but there is much more that we 
 should like to know. How, asks Dr. Savage, 
 in his Presidential Address to the Neurological 
 Society,* does this instability of nervous 
 system originate ? May it have begun through 
 faulty nutrition of some ancestor, so profound 
 that his germinal tissues suffered with the rest 
 of his body ? That might suggest a hope that 
 in time it might be rectified by reversing the 
 process. Or may it be that his germinal 
 tissues were old and effete when he under- 
 took the process of procreation ? Or is it, 
 after all, some deeply ingrained fault, origina- 
 
 * ' Brain,' vol. xx. 
 
3G ON HEREDITY IX RELATION TO DISEASE 
 
 ting we know not liow, and curable only by 
 extinction of the stock or by repeated cross- 
 in o-s witli others that are more stable ? We 
 cannot answer certainly. Xor can we always 
 tell what determines the special form of 
 neurosis in the different individuals, why 
 some should have epilepsy, some insanity, and 
 so forth ; nor why, as sometimes happens, 
 some one of these morbid manifestations 
 should repeat itself, and not alternate with 
 others. Melancholia, Dr. Savage* tells us, 
 is particularly apt to recur in several members 
 of a family, and Dr. Aldren Turner says the 
 same thing, I believe, of epilepsy.! IN^or yet 
 do we know why some members of a neuro- 
 pathic family should appear perfectly normal, 
 and some perhaps even better than their 
 fellow-men. Here we think of the old 
 saying that genius is allied to insanity. 
 Mendelian writers sometimes tell us that we 
 should learn the lesson of the blue Andalu- 
 sian fowl. That farmyard sermon teaches 
 us, inter alia, that from crossing two pure 
 
 * ' Brain,' vol. xx, p. 17. 
 
 t 'Epilepsy,' Ly Dr. Aldren Tiimer, p. 26; Macmillan, 
 1907. 
 
ON HEREDITY IX RELATION TO DISEASE 37 
 
 breeds which are considered undesirable a 
 monoTel may result of a desirable character. 
 May this happen with neurotic stocks ? Can 
 two such families atone for their existence 
 bj combining to produce a genius? One 
 would hardly care to advise the experiment, 
 and luckily our advice as to pairing is seldom 
 asked and still less often acted on. The 
 science of eugenics is still in its infancy ; let 
 us hope that when it becomes an active force 
 physicians will have acquired such know- 
 ledo'e as will enable them to take their 
 proper share in controlling it. Lastly, there 
 is the important inquiry. What relation have 
 these nervous manifestations, and the dia- 
 thesis in which they have their root, to other 
 diseases of more tangible nature, to gout, 
 rheumatism, tuberculosis, the febrile state, 
 etc.? That there are such relations, and some 
 rather close ones, this we know, Imt little 
 more. 
 
 The second way in which heredity mani- 
 fests itself as reo-ards nervous disease is 
 
 o 
 
 different. In this form a certain disease, 
 definite in type, whose identity as a rnle is 
 
38 ON HEREDITY IN TxELATION TO DISEASE 
 
 easily recognised, appears in several members 
 of a family; it may be in successive genera- 
 tions, it may be only in one generation. This 
 class constitutes the group known as family 
 diseases of the nervous system, which was 
 discussed before the College last summer in 
 a most interesting lecture by Professor 
 Raymond. Such family disease is by no 
 means limited to the nervous system, but in 
 that sphere numerous and remarkable ex- 
 amples of it are to be found. Friedreich's 
 ataxia is one of the best-known examples. 
 In this class of disease the precision with 
 which the features of the particular com- 
 plaint reproduce themselves is generally 
 remarkable, and contrasts strongly with the 
 shiftiuQf character of the neuroses which we 
 have just considered. There are, I know, 
 exceptions to this rule, which have been 
 much insisted upon lately, either where the 
 disease is incompletely developed in some 
 individuals, or where different types may 
 appear in different members of the same 
 family; but still, I think that, generally 
 speaking, the reproduction is fairly accurate, 
 
ox HEREDITY IN RELATION TO DISEASE 39 
 
 SO that the particular disease can be as easily 
 recognised as can tabes, disseminated scle- 
 rosis, or other non-family nervous disease. A 
 general neuropathic taint need not neces- 
 sarily exist in the family, though, of course, it 
 may. The majority and the best known of 
 these diseases present the clinical picture of a 
 slowly progressive incurable paralysis, which 
 may correspond anatomically to an exceed- 
 ingly definite degeneration of certain nerve 
 tracts. Thus Friedreich's disease affords us 
 an exquisite example of combined system 
 sclerosis beginning in the posterior columns, 
 then affecting the pyramidal tracts, and 
 involving in advanced cases the afferent 
 tracts to the cerebellum as well. Heredi- 
 tary spastic paraplegia has been shown by 
 Striimpell to depend on a degeneration of 
 the pyramidal tracts.* Yet the patients are 
 not l)orn with these lesions, so that we can- 
 not exactly call them malformations ; they 
 are born with an hereditary weakness of 
 
 * ComLined with a slighter degenenition of certain 
 ascending tracts, vide Striimpell, ' Arcliiv f. Psychiatrie,' 
 vol. X, 1880, and xvii, 1886, and ' Deutsch. Zeitschrift f'iir 
 Nervenlieilkunde,' 1893. 
 
40 ON HEREDITY IN EELATION TO DISEASE 
 
 these nervous tracts, wliicli break down 
 under tlie stress of living. The age at T\diich 
 symptoms begin differs hirgely in the diffe- 
 rent diseases ; the onset may be in early life, 
 in early or late adolescence (instances of all 
 these dates can be given in Friedreich's 
 disease) ; in middle life or even later, as in 
 Huntington's chorea or the spastic paraplegia 
 just quoted from Striimpell. It is strange to 
 think that a man can develop at that age a 
 disease which must have existed potentially 
 all his life. The date of onset may be in- 
 fluenced, too, within limits, by family pro- 
 clivity or circumstances ; in a series of 
 brothers and sisters it often repeats itself. 
 
 Now, though the presence of a definite 
 organic lesion and a progressive downward 
 course are the rule for these complaints, this 
 is not so for all of them. Contrast the here- 
 ditary chorea of Huntington, which is fatal, 
 and in which lesions of the cortex have been 
 found by Michell Clarke* and others, with 
 family tremor, which is not necessariW pro- 
 gressive, and for which we know no anatomical 
 
 * ' Brain,' vol. xx. 
 
ON HEREDITY IN RELATION TO DISEASE 41 
 
 basis. Contrast, too, in this respect, muscular 
 dystrophy, which may slowly reduce a patient 
 to the condition of a living skeleton with the 
 perverted condition of muscular contraction 
 known as myotonia congenita or Thomson's 
 
 disease. 
 
 Notice, too, that most remarkable family 
 disease called "periodic paralysis," in which 
 the patient experiences recurrent attacks of 
 paralysis, so complete that even the electrical 
 reactions of the muscles disappear; yet the 
 attack passes off and he is well in the intervals. 
 This affection has been traced back through 
 as many as five generations. There can 
 hardly be a gross lesion ; and the suggestion 
 has been made that some poison is at work, 
 perhaps produced by the patient's own faulty 
 metabolism; an "inborn error of metabolism " 
 like those with which our Croonian lecturer, 
 Dr. Grarrod, has made us acquainted. 
 
 In these family nervous diseases the curious 
 phenomenon of sex limitation is sometimes 
 seen, and generally in this sort, that females 
 are themselves not affected, yet they transmit 
 the disease. This was pointed out, I think, by 
 
42 ON HEREDITY IN RELzVTION TO DISEASE 
 
 Sir AYilliam Gowers,* in pseudo-liypertropliic 
 paralysis ; and in the remarkable pedigree of 
 peroneal atrophy published by Dr. Herring- 
 ham in 1889t it is a striking fact. Yet in 
 peroneal atrophy it is certainly not the rule ; 
 and in sundry other family diseases I do not 
 think it occurs at all. 
 
 Lastly, as to the essential nature of these 
 diseases. They have been called family 
 diseases, if I mistake not, in order to avoid 
 the distinct assertion that they are hereditary, 
 i. e. transmitted from ancestors. But why 
 should we not assert this ? It is true that 
 such disease may break out in a family of 
 brothers and sisters without obvious ancestral 
 taint; but in all these instances there is an 
 absence of other sufficient cause; and they 
 can be supplemented by quoting other fami- 
 lies in which we know the disease to have 
 been handed down. How, too, when cousins 
 are affected ? The common cause must then 
 lie further back than the parents or the 
 upbringing of one particular family. Indeed, 
 
 * ' Pseudo-hypertvopliic Muscular Paralysis,' pp. 21, 23, 
 Chiircliill, 1879. 
 t ' Brain,' vol. xi, p. 230. 
 
ON HEEEDITY IN EELATION TO DISEASE 43 
 
 if we refuse to call tliese complaints here- 
 ditary because we cannot always trace the 
 heredity, we should on the same ground 
 refuse to call them family affections. For 
 we often meet with isolated instances, 
 sporadic cases where only one member of a 
 family is affected. This is surprisingly fre- 
 quent in Friedreich's disease. Still, it is a 
 strange thing to witness when a disease, 
 hitherto unknown in a family, arises without 
 apparent cause, and involves in a progressive 
 paralysis one after another of the brothers 
 and sisters. What shall we call it ? Is it a 
 "mutation," a biological "sport"? Is the 
 germ-plasm just trying a change, stimulated, 
 it may be, by some untoward circumstance, 
 such, let us say, as alcoholism in the father ? 
 Or shall we suppose that the disease has 
 been in the ancestry all along, but hidden 
 away as a "recessive" character, so that if 
 we could push our researches far enough 
 back we mio-ht find it? Let us remember 
 the remarkable account given by Hutimeyer,* 
 where no less than four families of cousins 
 
 * ' Yircliow's Arcliiv,' Bel. 91. 
 
44 ON HEREDITY IN KELATIOX TO DISEASE 
 
 (in various degrees) were affected by Fried- 
 reich's disease — a sure enouo-li indication 
 that there was some ancestral taint. Yet no 
 case could be found among the ancestry till 
 in the fifth generation a record was found of 
 their common great-great-great-grandfather, 
 who, on account of his unsteady gait, had been 
 nicknamed " The Stumbler." 
 
 As to the actual pedigrees of these family 
 paralyses, we are beginning now to acquire 
 some tolerably complete ones, and it might 
 be thought that this is just the class of disease 
 which would lend itself to a Mendelian ex- 
 planation. But I understand that there are 
 considerable difficulties about this, so much, 
 indeed, that it has been suggested that 
 parental infection and not heredity is the 
 real cause. But what infection could pass 
 down for several generations, sometimes 
 skipping a generation, sometimes limiting 
 itself to the male sex ? For myself I cannot 
 imagine that, and I think that the key to this 
 lock must be provided by the laws of here- 
 dity, whatever those laws may be. 
 
 But I fear. Sir, that in pursuing the sub- 
 
ON HEREDITY IN RELATION TO DISEASE 45 
 
 ject of heredity I have already wandered too 
 far. How shall I, in conclusion, come back 
 to Harvey and to the College which he loved 
 so well ? Harvey himself in the presence of 
 a great subject did not shrink from metaphor. 
 He spoke of bodily conceptions and of con- 
 ceptions of the mind almost as if they were 
 one, and, in speaking of the generation and 
 inheritance of ideas, he says : " Democritus 
 and Eudoxus ' impregnated ' Epicurus, and 
 the four elements of Empedocles, Aristotle." 
 Is it, then, too fanciful to ask, how does this 
 College reproduce itself, and what laws of 
 inheritance are at work within it, from 
 generation to generation ? Now, we are told 
 that Nature has reserved the work of repro- 
 duction to herself, and left parents little to 
 do in determining the inborn characteristics 
 of their offspring ; but we in this College have 
 the privilege of actually choosing our suc- 
 cessors. This inestimable privilege we dele- 
 gate to no one, not even to a body of exa- 
 miners ; and Ave choose our new Fellows by 
 co-option — the best of methods when well 
 exercised, the worst when exercised badly. 
 
46 ON HEREDITY IN RELATION TO DISEASE 
 
 Rightly, tlien, are we reminded each year of 
 the responsibility which rests upon each of 
 us in this respect, and rightly is that meeting 
 of the Council, in which recommendations for 
 the Fellowship are winnowed out, held to be 
 of supreme importance. Is there, then, no 
 continuity in the successive generations of 
 the College ? Does each depend on the mere 
 caprice or individual likings of its prede- 
 cessor ? No ; for we, too, have our " germinal 
 plasm," which is continuous and everlasting ; 
 I mean the noble principles upon which the 
 College is founded and by which it has ever 
 been maintained — zeal for the pursuit of truth, 
 whether in medicine or in other science ; the 
 dedication of knowledge thus acquired to the 
 relief of human sickness and pain ; self-efface- 
 ment in the interests of the profession and of 
 the College to which we belong ; and above 
 all, the spirit of unity and amity. For 
 Harvey's last and best exhortation is : '* To 
 continue in mutual love and affection among 
 ourselves," an exhortation which he enforces 
 with the weighty words, " Concordia res parvge 
 crescunt, discordia magnge dilabuntur." 
 
ADLARD AND SON, IMPR., LONDON AND DORKING. 
 
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