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Heredity and Disease
248
EDITORIAL ARTICLES.
Summarising the above eighty-seven cases, I think that it will be acknowledged that the results are quite as satisfactory as were those which were published in the Journal last year. Altogether the operation has been performed ninety-seven times, as in ten cases both legs were operated upon. In no case up to the present have I been able to trace a ruptured tendon or sloughing of the hoof unless the external plantar nerve had also been divided. At least thirteen of the cases have now been at regular work for about eighteen months since the operation, whilst ten others have been working for more than twelve months. I am more firmly convinced than before that for old-standing lameness, where due to splints, exostoses anywhere on the inside of the leg, chronically sprained, thickened, and painful tendons, or cases of that kind which cause pain by pressing on the adjacent nerve structures, after all other treatment has failed, median neurectomy is the operation which will often give the animal a new lease of life and usefulness. That the whole of the sensation is not removed from the inside of the limb can readily be demonstrated by pricking the skin with a pin, and also by the fact of a corn, when very bad, causing lameness; also by Case 22, in which a wound on the inside of the coronet, and Case 30, in which severe thrush, each caused temporary lameness. That excision of the median nerve does not affect the healing of wounds in the parts below on the inside, is shown by those cases in which wounds were surgically or accidentally inflicted after the operation. Case 24, in which a neuroma formed on the median nerve, is worth a special note, as M. Pellerin, in his pamphlet on median neurectomy, draws especial attention to its rarity, as evidenced by the fact that he has never met with or heard of a case.
ED I TORIAL
ART I CLES.
HEREDITY AND DISEASE.
IT could not, without a sacrifice of candour, be said that the discussion on "heredity in its relations to the diseases of animals" at the recent annual meeting of the National Veterinary Association has shed much fresh light on that admittedly obscure subject. It would perhaps have been unreasonable to expect that the occasion would do much to elucidate what may be termed the mechanism of heredity, but one might not unnaturally have looked for some new facts and observations bearing on what is certainly the all-important question in connection with the subject of heredity, viz., What diseases of the lower animals ought to be classed as hereditary? We cannot help thinking that an undue amount of attention was given both by the essayist and by some of those who took part in
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the discussion to the ingenious theories that have been put forward to explain the mechanism of heredity, for, as a matter of fact, such of these so-called theories of heredity as have any claim to verisimilitude scarcely serve to make the mechanism of heredity one whit clearer to the ordinary mind. As Professor Dewar has shown in the essay which formed the basis of the discussion at the ~ ational Meeting, the cell is by no means the simple nucleated mass of homogeneous protoplasm which Schwm1n supposed it to be. Both nucleus and cellsubstance have a comparatively complex structure, and the act of fertilisation is not a simple case of fusion of a male and a female cell, but the union of definite elements--the chromosomes or idants-of the male spermatozoid with like elements of the female cell or ovum. But admitting this to be true, will anyone say that it dispels, or in any appreciable degree diminishes, the mystery of heredity ? The ovum and the spermatozoid have compressed within their microscopic limits the minutest characters of the parent, and in the act of fertilisation these are carried over to the new individual, but the phenomenon is equally mysterious whether we regard the cell-substance or the nuclear chromatin as the vehicle by which the parental characters are transmitted. No theory yet put forward enables us to form a clear conception of how it is that the fertilised ovum of a cow culminates in the production of a new individual of the bovine species, and not in a foal or lamb, and until that, which is the simplest problem of heredity, has been solved we cannot expect to find any clue to the hereditary transmission of morbid characters from a study of the act of fertilisation or the structure of the germ cells. In the discussion of speculative theories regarding the mechanism of heredity, it appears to be often forgotten that we owe to observation and experiment all the accurate information that we possess concerning the transmission of characters and conditions from parent to offspring. We cannot even distinguish the ovum of a mare from that of a cow, and it is incredible that our microscopic analysis of the ovum or spermatozoid will ever carry us so far as to enable us to discover in them the rudiments of parental defects or morbid characters in process of transmission to the embryo. If splints, or spavins, or side-bones are hereditary, there is assuredly only one way in which the fact can be proved, viz., by patiently collating the results of breeding from animals with these defects. A t the outset of his paper on heredity in relation to disease Professor Dewar has thought it necessary to utter a warning against confusing the terms" hereditary" and" congenital," but he omitted to define one other term regarding which it was equally necessary to avoid misunderstanding, viz., disease. Clearly there can be no useful discussion regarding the role of heredity in the production of "disease" between persons who use that word in a different sense. In the absence of a definition on the part of the essayist and the others who
EDITORIAL ARTICLES.
took part in the discussion at Reading, we have only the context to guide us as to what they understood by disease, but we note one or two passages which suggest that the speakers were using the word in a new and entirely inadmissible sense. For example, among the list of diseases said to be "undoubtedly hereditary," we find diarrhcea and colic, which makes it evident that it is not disease, but a diminished resistance to the cause of disease, that is here said to be hereditary. People in the habit of using terms loosely may be content to make one word suffice both for disease and for what is usually termed predisposition, but if utter confusion in the discussion of heredity is to be avoided, a clear distinction must be drawn between the two conditions. \Vhat is disease? There is only one way by which we can define that, viz., by first defining health. Health is that condition which, on examination of the largest available number of individuals, is found to be the common or prevailing one. This applies equally to structure and function. The normal or healthy structure of any individual is that which observation has shown to be the common one among other animals of the same kind, and, in like manner, a condition of health implies that the functions'of the various organs are performed as they are in the majority of other animals of the same species. Health being thus defined, we agree to call any departure from it disease. In other words, a part or organ is diseased when in structure or function it departs from the common or prevailing type. What, it may next be asked, is predisposition? In order to answer that it is necessary to observe that what, according to the above definition, we term disease, is probably never spontaneous. In the immense majority of cases the structural alterations and functional derangements which we regard as disease are the direct effects of agents acting on the part or organ affected, or they represent the reaction of the tissues of the body to such agents. For example, inflammation of the intestinal mucous membrane may be the direct result of, and diarrhcea the reaction to, a poison accidentally administered. Fracture of a bone may be the direct result of mechanical violence, and the formation of a callus the reaction of the bone to the lllJury. Glanders is the result of the invasion of the body by the germ of glanders, and the glanders lesions for the most part represent the reaction of the invaded tissues to the glanders bacillus. But the resistance offered to direct injury, whether by a blow or a pathogenic organism, varies from individual to individual, and so also does the reaction of the tissues. \Vhere the resistance offered is slight we may say that the individual has a predisposition to that particular disease. Thus, an animal with thin or weak bones is predisposed to fracture, and one whose tissues offer a feeble reaction to the glanders bacillus is predisposed to glanders. These considerations will serve to show how necessary it is to draw a sharp distinction between predisposition and disease, and
EDITORIAL ARTICLES.
in the light of them it becomes apparent that while only a small number of diseases can be said to be strictly inherited, the hereditary transmission of predisposition to disease is likely to be the rule. Indeed, it appears that one must either altogether deny the transmission of predisposition, or admit that it must be universal in its operation. Countless observations prove that characters which we regard as the most trivial in the individual, such as the quality of the voice, tricks of gesture, and the most minute details of features, may be passed on from parent to offspring, and therefore on a priori grounds it would be unreasonable to deny that the qualities of cells and tissues which determine the degree of resistance offered to the causes of disease, are just as lik€ly to be transmitted. It must be admitted, however, that while the principle of hereditary transmission of predisposition is probably universal in its operation, there are many diseases in which it almost escapes observation. \Vhen what may be called the average resistance of the species to the cause of any given disease is very low, then the transmission of varying degrees of predisposition is apt to be lost sight of. On the other hand, where the average resistance of the species to the cause of a disease is high, the occurrence of varying degrees of susceptibility in different individuals forces itself on our attention. For example, the average resistance of animals of the bovine species to cattle plague is slight, and we therefore seldom notice any marked predisposition to that disease in individual cattle; the average resistance offered by the same species to foot-and-mouth disease is considerable, and in almost e\'ery outbreak one cannot fail to notice varying degrees of susceptibility in different individuals. Nevertheless, it is probable that predisposition varies from individual to individual just as much in the olle case as in the other. From a practical point of view predisposition is important only when the intensity of the cause of disease, and the degree of resistance offered by the species are so balanced as to bring out distinct degrees of predisposition in different individuals, and even then predisposition to disease ceases to be of practical importance if the cause of the disease can be generally avoided. For example, if, as is frequently supposed, the formation of splints and other exostoses in connection with the bones of the extremities is the result of concussion, there is abundant evidence in favour of varying degrees of predisposition, and since in the ordinary course of a horse's work concussion is unavoidable, it is manifestly indicated to avoid breeding from animals that have developed such bone diseases. Or, to take another illustration, if Professor Dewar is correct in supposing that side-bones are induced by wearing shoes with high calkins, there must be a varying predisposition to side-bones, for every horse shod with high calkins does not develop that abnormality. Hence, it would be indicated to discard for breeding purposes animals affected with side-bones-that
EDITORIAL ARTICLES.
is, assuming that their progeny must be shod with high calkins. But although Professor Dewar himself believes that cattle exhibit varying degrees of predisposition to rinderpest, he would hardly recommend that farmers should cease to breed from all animals save those that have an unusual degree of immunity to that disease. In this and in many other cases varying predisposition may be neglected by the breeder, because even when most highly developed the powers of resistance to the cause of the disease are not such as to be practically useful. That is why it would be absurd to disqualify an animal for breeding because it had experienced fracture of a bone or sprain of a tendon, although, by the way, we observe that Professor Dewar includes sprains in his list of hereditary diseases. As was to be expected, tuberculosis received a good deal of attention at Reading, and we observe with regret that a considerable number of the speakers reaffirmed their belief in the hereditary nature of that disease. For the most part the statements on this subject were mere declarations of faith, unsupported by any arguments, and therefore not calling for refutation. \\There any show of reasoning in support of the hereditary nature of tuberculosis was made, it took the form of the oft exposed fallacy of inferring hereditary transmission from the occurrence of tuberculosis in the progeny of tuberculous parents. This is a method of reasoning which is excusable on the part of anyone who denies that tuberculosis may be spread by contact, but it is difficult to understand how it can be seriously advanced by those who admit that in favourable circumstances the disease is contagious. Much of what was said on the subject of tuberculosis at the recent meeting of the National Association suggests that there are people who regard the retention of beliefs acquired in early life as a sort of virtue. In our view, beliefs and opinions should be held just as long as the available evidence appears to justify them, and no longer. Twenty years ago a belief in the hereditary transmission of tuberculosis was general, and the available knowledge of the period appeared to justify it. Long experience had proved that a far larger proportion of cases of tuberculosis occurred among the progeny of tuberculous parents than among those born of healthy parents, and since Koch's bacillus and the opportunities for its transference from animal to animal by contagion had not then been recognised, it was perfectly natural to suppose that tuberculosis was frequently or generally passed on from parent to offspring at the act of conception. But when it was proved that tuberculosis was due to a specific germ, and experiment had shown that it was possible to infect animals with it at will, it, of course, became necessary to inquire whether infection after birth was not accountable for a large proportion of the cases previously regarded as hereditary. This could obviously be settled by post-mortem examination of the newly born progeny of tubercu-
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lous parents, and the information derived from that source has made it quite impossible for anyone to maintain that any considerable proportion of animals of the human or bovine species come into the world with evidence of tuberculosis in any of their organs. It is true that those who have pinned their faith to the view that tuberculosis is generally inherited do not admit that the absence of visible lesions from a new-born animal is conclusive evidence of freedom from tuberculosis, for, they say, the bacillus may be there in a state of dormant vitality. To say that this is a perfectly gratuitous assumption is not enough-it is a conclusion entirely opposed to such evidence as we can obtain on the point. Every experiment of the kind that has hitherto been made justifies the assertion that when tubercle bacilli are introduced into the tissues of an animal, whether that animal be newly born or aged, these bacilli either multiply and excite the formation of tuberculous lesions, or they promptly perish. Finally, as bearing on this point, it may be mentioned that tuberculin, which is a more delicate test for the existence of tuberculosis than the most painstaking post-mortem examination, has already shown that the progeny of tuberculous cows or bulls are rarely tuberculous at birth.1 In taking leave of this question an apology almost seems necessary for having set out once more the reasons for declining to admit that the hereditary transmission of tuberculosis plays a role of any importance in the spread of the disease. Foals have been born affected with glanders, and indubitable cases of congenital strangles are on record, but we could not treat seriously the argument that the hereditary transmission of these diseases is of practical importance, or that we ought to take account of it in devising measures of prevention. As we have already hinted, the belief that tuberculosis is generally transmitted by inheritance appears to be an article of faith with those who hold it, and it is not to be upset by reasoning. In that part of Professor Dewar's essay which treats of heredity in relation to tuberculosis, the author does not give his views regarding the hereditary transmission of the disease, but he does make it clear that he attaches great importance to the hereditary transmission of predisposition as a contributory cause of the present prevalence of tuberculosis among cattle. He says: "There is undoubtedly a predisposition to the disease communicated to the progeny; and the more generations affected with the disease the greater is the predisposition to it, until ultimately they cease to surviv,e to procreate their species." 1 Assuming that 20 per cent. of all the cows in Great Britain are tuberculous, and that 1 per cent. of the calves born of tuberculous parents are diseased at birth-an estimate which we believe to be much too high-it would follow that not more than 1 calf in 500 inherits tuberculosis from its parent. And it ought to be pointed out that even this estimate is calculated to convey an exaggerated impression of the rOle which heredity plays in the transmission of tuberculosis among our cattle, since one iR apt to overlook the fact that p~bably only a small proportion of calves tuberculous at their birth reach an age at which they can be used for breeding purposes. '
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The opposite view has, he says, been maintained in this country by those whom he contemptuously terms the" pure microbiologists:" The passage is a little ambiguous, for it leaves it doubtful whether Professor Dewar means that the "pure microbiologists "-whoever they may be-deny that a predisposition to tuberculosis is transmitted by heredity, or merely refuse their assent to the statement that the predisposition increases with the number of generations affected until the strain is naturally exterminated. If the latter meaning is the one intended to be conveyed, we can only say that we would prefer to enrol ourselves on the side of the pure microbiologists. It is significant that Professor Dewar could not find evidence in support of this view of the deadly nature of tUberculosis nearer than Auvergne. It deserves to be quoted at length :-" Sanson relates at length a case in which a number of Devon cows and bulls, which had been imported, were removed from the Agricultural Institute at Versailles to a model dairy in the mountains of Auverglle, at Saint-Angeau, in the department of Cantal. They were introduced amongst a herd of the finest Auvergnate cows, the purpose being to cross the native cows with the Devon bulls to improve the milking qualities of the animals, but it was a failure. In a few years all the Devons, male and female, died out from tuberculosis, and when Sanson visited the dairy in 1868, the crosses had all died out except one, while the pure Auvergnates remained healthy. These animals were all stabled together, all grazed together on the same pastures, and Sanson contends that if the dissemination of the disease had been entirely due to contagion the Auvergnate cows would also have suffered, whereas all without exception escaped." It will be observed that while Professor Dewar quotes this extraordinary case as evidence of a growing predisposition in successive generations affected with tuberculosis, Sanson himself obviously interpreted the facts as evidence of the hereditary transmission of the disease itself, for, of course, if there was a great difference of predisposition between the two races, the fact that all the animals of the Auvergne breed escaped, while all the Devons contracted the disease, was in no way opposed to the view that the spread of the disease among the latter was entirely due to contagion. It ought also to be noted that this happened thirty years ago, before Koch's bacillus had been thought of, and before the days of tuberculin. Did Mr Sanson verify the cause of death in everyone of the Devons and crosses, and how did he know that none of the Auvergne animals were affected? We leave it to the clinicians, who, according to Professor Dewar, are all on his side, to say whether it is in conformity with their experience that tuberculosis is such a deadly disease that it will exterminate a herd of Devons or any other breed in the course of a few years. In the very paper from which we are quoting it is said that tuberculosis among cattle is not a very contagious disease, and yet we
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are asked to believe that in this Auvergne herd it was so contagious that in a few years every Devon and cross-bred animal in the herd became affected! Our incredulity is not with regard to the number of animals that contracted the disease, but \vith regard to its invariably fatal Gourse. We would not like to say with Professor Dewar that tuberculosis is not a very contagious disease, but we would without hesitation assert that even among Devons it is not a very fatal one, and that there has not yet been produced any evidence to show that predisposition to tuberculosis is increased by an attack of the disease, or that the reinforced predisposition is transmitted to the next generation. As to denying the occurrence of predisposition, that is another matter. We never heard of a microbiologist in this or any other country who did not believe that animals of different breeds and families, and even individuals of the same family, exhibit varying degrees of resistance when they become the subjects of tuberculosis, and that the qualities of cells and tissues which underlie this power of resistance are likely to be transmitted by heredity. But, unfortunately, this resistance varies within rather narrow limits, and in the case of our valuable breeds it never amounts to absolute immunity, or even to such a degree of insusceptibility as will enable them to indefinitely withstand the risks of infection when they are housed with other tuberculous animals. There does not appear to be much cogency in citing the resistance of Auvergne cattle to tuberculosis, unless it is meant to suggest that the owners of our pedigree herds of shorthorns, Devons, or Aberdeen-Angus cattle should di~card these, and replace them by some stlmi-wild or mountain breed possessing more marked powers of resistance to tuberculosis. The problem to be solved is to free our existing herds from the disease without sacrificing those desirable qualities which have been built up as characters of the breed by long-continued selection. We may admit that most of our most valued strains of cattle are readily infected with tuberculosis, but those who own them would much rather keep them with this defect than deteriorate the strain by crossing with an inferior breed absolutely immune against the disease, if such a breed could be found. vVe can imagine someone saying that it is not necessary to go outside any of the strains to find animals without this fatal predisposition to tuberculosis, and that by steadily selecting such animals for breeding, and discarding those affected with tuberculosis and all their progeny, it would be possible in the course of a few years to create a herd immune against the disease. It is, of course, not possible to absolutely disprove such a view, but it is easy to show how slender are the foundations on which any such expectations are built. How, in the first place, are we to ascertain which of .the animals in any given herd are devoid of predisposition? Are we to regard present
EDITORIAL ARTICLES.
freedom from tuberculosis on the part of an animal as evidence of immunity? The supposition is too absurd, for, as has already been mentioned, the tuberculin test if carried out soon after birth would by this method of reasoning prove that almost all animals of the bovine species are immune. Or are we to take freedom of several successive generations as the only evidence of insusceptibility to tuberculosis? That would be an impracticable proposal, for' in most cases we could not obtain the assurance that the progenitors of an animal for even two generations ha~ been free from tuberculosis. In short, it is a great fallacy to assume that even in the same herd it is solely or mainly the varying degrees of predisposition that determine which animals shall become the victims of tuberculosis. As w~1l might it be maintained that it is always the most susceptible ho-;'se that contracts glanders, or credit the animals that do not react to mallein in an outbreak of glanders with immunity against that disease. N or can the predisposition to tuberculosis be detected by a study of conformation, though it appears that there are still to be found clinicians who believe the opposite. Tuberculin has taught us that the narrow chest and other points of conformation, which were once accepted as evidence of a (' phthisical constitution," are of no value whatever as indications of special predisposition to tuberculosis. Such characters are the effects of tuberculosis, not the predisposing cause of that disease, and the most splendid type of conformation is quite compatible with the usual degree of predisposition to tuberculous infection. That these statements are true will not be denied by anyone who has had much experience in the use of tuberculin as a test for tuberculosis in cattle. Professor Dewar finds fault with those who say that if the sources of infection are cut off from healthy animals predisposition may be disregarded, and he remarks that" this may be quite true theoretically, but it is not a very practical way of dealing with the matter." To that it may be replied that if a method is correct in theory it cannot be wrong in practice. \Vhat is the alternative method? To breed only from animals that are free from tuberculosis, and neglect the risk of contagion! That, it may safely be asserted, is wrong in theory, and it would be disastrous in practice. The only sound advice to give to those who are fortunate enough to possess healthy herds is to warn them not to ascribe their present freedom from tuberculosis to absence of predisposition on the part of their animals, or to neglect any reasonable precaution against infection. In like manner, we are entitled to tell those who own herds already affected that the one condition necessary to get rid of the disease is to make a permanent separation between the diseased and the healthy, and that, no matter what the breed or strain may be, a herd may be made and kept free from tuberculosis. ,
EDITORIAL ARTICLES.
Summarising the above eighty-seven cases, I think that it will be acknowledged that the results are quite as satisfactory as were those which were published in the Journal last year. Altogether the operation has been performed ninety-seven times, as in ten cases both legs were operated upon. In no case up to the present have I been able to trace a ruptured tendon or sloughing of the hoof unless the external plantar nerve had also been divided. At least thirteen of the cases have now been at regular work for about eighteen months since the operation, whilst ten others have been working for more than twelve months. I am more firmly convinced than before that for old-standing lameness, where due to splints, exostoses anywhere on the inside of the leg, chronically sprained, thickened, and painful tendons, or cases of that kind which cause pain by pressing on the adjacent nerve structures, after all other treatment has failed, median neurectomy is the operation which will often give the animal a new lease of life and usefulness. That the whole of the sensation is not removed from the inside of the limb can readily be demonstrated by pricking the skin with a pin, and also by the fact of a corn, when very bad, causing lameness; also by Case 22, in which a wound on the inside of the coronet, and Case 30, in which severe thrush, each caused temporary lameness. That excision of the median nerve does not affect the healing of wounds in the parts below on the inside, is shown by those cases in which wounds were surgically or accidentally inflicted after the operation. Case 24, in which a neuroma formed on the median nerve, is worth a special note, as M. Pellerin, in his pamphlet on median neurectomy, draws especial attention to its rarity, as evidenced by the fact that he has never met with or heard of a case.
ED I TORIAL
ART I CLES.
HEREDITY AND DISEASE.
IT could not, without a sacrifice of candour, be said that the discussion on "heredity in its relations to the diseases of animals" at the recent annual meeting of the National Veterinary Association has shed much fresh light on that admittedly obscure subject. It would perhaps have been unreasonable to expect that the occasion would do much to elucidate what may be termed the mechanism of heredity, but one might not unnaturally have looked for some new facts and observations bearing on what is certainly the all-important question in connection with the subject of heredity, viz., What diseases of the lower animals ought to be classed as hereditary? We cannot help thinking that an undue amount of attention was given both by the essayist and by some of those who took part in
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the discussion to the ingenious theories that have been put forward to explain the mechanism of heredity, for, as a matter of fact, such of these so-called theories of heredity as have any claim to verisimilitude scarcely serve to make the mechanism of heredity one whit clearer to the ordinary mind. As Professor Dewar has shown in the essay which formed the basis of the discussion at the ~ ational Meeting, the cell is by no means the simple nucleated mass of homogeneous protoplasm which Schwm1n supposed it to be. Both nucleus and cellsubstance have a comparatively complex structure, and the act of fertilisation is not a simple case of fusion of a male and a female cell, but the union of definite elements--the chromosomes or idants-of the male spermatozoid with like elements of the female cell or ovum. But admitting this to be true, will anyone say that it dispels, or in any appreciable degree diminishes, the mystery of heredity ? The ovum and the spermatozoid have compressed within their microscopic limits the minutest characters of the parent, and in the act of fertilisation these are carried over to the new individual, but the phenomenon is equally mysterious whether we regard the cell-substance or the nuclear chromatin as the vehicle by which the parental characters are transmitted. No theory yet put forward enables us to form a clear conception of how it is that the fertilised ovum of a cow culminates in the production of a new individual of the bovine species, and not in a foal or lamb, and until that, which is the simplest problem of heredity, has been solved we cannot expect to find any clue to the hereditary transmission of morbid characters from a study of the act of fertilisation or the structure of the germ cells. In the discussion of speculative theories regarding the mechanism of heredity, it appears to be often forgotten that we owe to observation and experiment all the accurate information that we possess concerning the transmission of characters and conditions from parent to offspring. We cannot even distinguish the ovum of a mare from that of a cow, and it is incredible that our microscopic analysis of the ovum or spermatozoid will ever carry us so far as to enable us to discover in them the rudiments of parental defects or morbid characters in process of transmission to the embryo. If splints, or spavins, or side-bones are hereditary, there is assuredly only one way in which the fact can be proved, viz., by patiently collating the results of breeding from animals with these defects. A t the outset of his paper on heredity in relation to disease Professor Dewar has thought it necessary to utter a warning against confusing the terms" hereditary" and" congenital," but he omitted to define one other term regarding which it was equally necessary to avoid misunderstanding, viz., disease. Clearly there can be no useful discussion regarding the role of heredity in the production of "disease" between persons who use that word in a different sense. In the absence of a definition on the part of the essayist and the others who
EDITORIAL ARTICLES.
took part in the discussion at Reading, we have only the context to guide us as to what they understood by disease, but we note one or two passages which suggest that the speakers were using the word in a new and entirely inadmissible sense. For example, among the list of diseases said to be "undoubtedly hereditary," we find diarrhcea and colic, which makes it evident that it is not disease, but a diminished resistance to the cause of disease, that is here said to be hereditary. People in the habit of using terms loosely may be content to make one word suffice both for disease and for what is usually termed predisposition, but if utter confusion in the discussion of heredity is to be avoided, a clear distinction must be drawn between the two conditions. \Vhat is disease? There is only one way by which we can define that, viz., by first defining health. Health is that condition which, on examination of the largest available number of individuals, is found to be the common or prevailing one. This applies equally to structure and function. The normal or healthy structure of any individual is that which observation has shown to be the common one among other animals of the same kind, and, in like manner, a condition of health implies that the functions'of the various organs are performed as they are in the majority of other animals of the same species. Health being thus defined, we agree to call any departure from it disease. In other words, a part or organ is diseased when in structure or function it departs from the common or prevailing type. What, it may next be asked, is predisposition? In order to answer that it is necessary to observe that what, according to the above definition, we term disease, is probably never spontaneous. In the immense majority of cases the structural alterations and functional derangements which we regard as disease are the direct effects of agents acting on the part or organ affected, or they represent the reaction of the tissues of the body to such agents. For example, inflammation of the intestinal mucous membrane may be the direct result of, and diarrhcea the reaction to, a poison accidentally administered. Fracture of a bone may be the direct result of mechanical violence, and the formation of a callus the reaction of the bone to the lllJury. Glanders is the result of the invasion of the body by the germ of glanders, and the glanders lesions for the most part represent the reaction of the invaded tissues to the glanders bacillus. But the resistance offered to direct injury, whether by a blow or a pathogenic organism, varies from individual to individual, and so also does the reaction of the tissues. \Vhere the resistance offered is slight we may say that the individual has a predisposition to that particular disease. Thus, an animal with thin or weak bones is predisposed to fracture, and one whose tissues offer a feeble reaction to the glanders bacillus is predisposed to glanders. These considerations will serve to show how necessary it is to draw a sharp distinction between predisposition and disease, and
EDITORIAL ARTICLES.
in the light of them it becomes apparent that while only a small number of diseases can be said to be strictly inherited, the hereditary transmission of predisposition to disease is likely to be the rule. Indeed, it appears that one must either altogether deny the transmission of predisposition, or admit that it must be universal in its operation. Countless observations prove that characters which we regard as the most trivial in the individual, such as the quality of the voice, tricks of gesture, and the most minute details of features, may be passed on from parent to offspring, and therefore on a priori grounds it would be unreasonable to deny that the qualities of cells and tissues which determine the degree of resistance offered to the causes of disease, are just as lik€ly to be transmitted. It must be admitted, however, that while the principle of hereditary transmission of predisposition is probably universal in its operation, there are many diseases in which it almost escapes observation. \Vhen what may be called the average resistance of the species to the cause of any given disease is very low, then the transmission of varying degrees of predisposition is apt to be lost sight of. On the other hand, where the average resistance of the species to the cause of a disease is high, the occurrence of varying degrees of susceptibility in different individuals forces itself on our attention. For example, the average resistance of animals of the bovine species to cattle plague is slight, and we therefore seldom notice any marked predisposition to that disease in individual cattle; the average resistance offered by the same species to foot-and-mouth disease is considerable, and in almost e\'ery outbreak one cannot fail to notice varying degrees of susceptibility in different individuals. Nevertheless, it is probable that predisposition varies from individual to individual just as much in the olle case as in the other. From a practical point of view predisposition is important only when the intensity of the cause of disease, and the degree of resistance offered by the species are so balanced as to bring out distinct degrees of predisposition in different individuals, and even then predisposition to disease ceases to be of practical importance if the cause of the disease can be generally avoided. For example, if, as is frequently supposed, the formation of splints and other exostoses in connection with the bones of the extremities is the result of concussion, there is abundant evidence in favour of varying degrees of predisposition, and since in the ordinary course of a horse's work concussion is unavoidable, it is manifestly indicated to avoid breeding from animals that have developed such bone diseases. Or, to take another illustration, if Professor Dewar is correct in supposing that side-bones are induced by wearing shoes with high calkins, there must be a varying predisposition to side-bones, for every horse shod with high calkins does not develop that abnormality. Hence, it would be indicated to discard for breeding purposes animals affected with side-bones-that
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is, assuming that their progeny must be shod with high calkins. But although Professor Dewar himself believes that cattle exhibit varying degrees of predisposition to rinderpest, he would hardly recommend that farmers should cease to breed from all animals save those that have an unusual degree of immunity to that disease. In this and in many other cases varying predisposition may be neglected by the breeder, because even when most highly developed the powers of resistance to the cause of the disease are not such as to be practically useful. That is why it would be absurd to disqualify an animal for breeding because it had experienced fracture of a bone or sprain of a tendon, although, by the way, we observe that Professor Dewar includes sprains in his list of hereditary diseases. As was to be expected, tuberculosis received a good deal of attention at Reading, and we observe with regret that a considerable number of the speakers reaffirmed their belief in the hereditary nature of that disease. For the most part the statements on this subject were mere declarations of faith, unsupported by any arguments, and therefore not calling for refutation. \\There any show of reasoning in support of the hereditary nature of tuberculosis was made, it took the form of the oft exposed fallacy of inferring hereditary transmission from the occurrence of tuberculosis in the progeny of tuberculous parents. This is a method of reasoning which is excusable on the part of anyone who denies that tuberculosis may be spread by contact, but it is difficult to understand how it can be seriously advanced by those who admit that in favourable circumstances the disease is contagious. Much of what was said on the subject of tuberculosis at the recent meeting of the National Association suggests that there are people who regard the retention of beliefs acquired in early life as a sort of virtue. In our view, beliefs and opinions should be held just as long as the available evidence appears to justify them, and no longer. Twenty years ago a belief in the hereditary transmission of tuberculosis was general, and the available knowledge of the period appeared to justify it. Long experience had proved that a far larger proportion of cases of tuberculosis occurred among the progeny of tuberculous parents than among those born of healthy parents, and since Koch's bacillus and the opportunities for its transference from animal to animal by contagion had not then been recognised, it was perfectly natural to suppose that tuberculosis was frequently or generally passed on from parent to offspring at the act of conception. But when it was proved that tuberculosis was due to a specific germ, and experiment had shown that it was possible to infect animals with it at will, it, of course, became necessary to inquire whether infection after birth was not accountable for a large proportion of the cases previously regarded as hereditary. This could obviously be settled by post-mortem examination of the newly born progeny of tubercu-
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lous parents, and the information derived from that source has made it quite impossible for anyone to maintain that any considerable proportion of animals of the human or bovine species come into the world with evidence of tuberculosis in any of their organs. It is true that those who have pinned their faith to the view that tuberculosis is generally inherited do not admit that the absence of visible lesions from a new-born animal is conclusive evidence of freedom from tuberculosis, for, they say, the bacillus may be there in a state of dormant vitality. To say that this is a perfectly gratuitous assumption is not enough-it is a conclusion entirely opposed to such evidence as we can obtain on the point. Every experiment of the kind that has hitherto been made justifies the assertion that when tubercle bacilli are introduced into the tissues of an animal, whether that animal be newly born or aged, these bacilli either multiply and excite the formation of tuberculous lesions, or they promptly perish. Finally, as bearing on this point, it may be mentioned that tuberculin, which is a more delicate test for the existence of tuberculosis than the most painstaking post-mortem examination, has already shown that the progeny of tuberculous cows or bulls are rarely tuberculous at birth.1 In taking leave of this question an apology almost seems necessary for having set out once more the reasons for declining to admit that the hereditary transmission of tuberculosis plays a role of any importance in the spread of the disease. Foals have been born affected with glanders, and indubitable cases of congenital strangles are on record, but we could not treat seriously the argument that the hereditary transmission of these diseases is of practical importance, or that we ought to take account of it in devising measures of prevention. As we have already hinted, the belief that tuberculosis is generally transmitted by inheritance appears to be an article of faith with those who hold it, and it is not to be upset by reasoning. In that part of Professor Dewar's essay which treats of heredity in relation to tuberculosis, the author does not give his views regarding the hereditary transmission of the disease, but he does make it clear that he attaches great importance to the hereditary transmission of predisposition as a contributory cause of the present prevalence of tuberculosis among cattle. He says: "There is undoubtedly a predisposition to the disease communicated to the progeny; and the more generations affected with the disease the greater is the predisposition to it, until ultimately they cease to surviv,e to procreate their species." 1 Assuming that 20 per cent. of all the cows in Great Britain are tuberculous, and that 1 per cent. of the calves born of tuberculous parents are diseased at birth-an estimate which we believe to be much too high-it would follow that not more than 1 calf in 500 inherits tuberculosis from its parent. And it ought to be pointed out that even this estimate is calculated to convey an exaggerated impression of the rOle which heredity plays in the transmission of tuberculosis among our cattle, since one iR apt to overlook the fact that p~bably only a small proportion of calves tuberculous at their birth reach an age at which they can be used for breeding purposes. '
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The opposite view has, he says, been maintained in this country by those whom he contemptuously terms the" pure microbiologists:" The passage is a little ambiguous, for it leaves it doubtful whether Professor Dewar means that the "pure microbiologists "-whoever they may be-deny that a predisposition to tuberculosis is transmitted by heredity, or merely refuse their assent to the statement that the predisposition increases with the number of generations affected until the strain is naturally exterminated. If the latter meaning is the one intended to be conveyed, we can only say that we would prefer to enrol ourselves on the side of the pure microbiologists. It is significant that Professor Dewar could not find evidence in support of this view of the deadly nature of tUberculosis nearer than Auvergne. It deserves to be quoted at length :-" Sanson relates at length a case in which a number of Devon cows and bulls, which had been imported, were removed from the Agricultural Institute at Versailles to a model dairy in the mountains of Auverglle, at Saint-Angeau, in the department of Cantal. They were introduced amongst a herd of the finest Auvergnate cows, the purpose being to cross the native cows with the Devon bulls to improve the milking qualities of the animals, but it was a failure. In a few years all the Devons, male and female, died out from tuberculosis, and when Sanson visited the dairy in 1868, the crosses had all died out except one, while the pure Auvergnates remained healthy. These animals were all stabled together, all grazed together on the same pastures, and Sanson contends that if the dissemination of the disease had been entirely due to contagion the Auvergnate cows would also have suffered, whereas all without exception escaped." It will be observed that while Professor Dewar quotes this extraordinary case as evidence of a growing predisposition in successive generations affected with tuberculosis, Sanson himself obviously interpreted the facts as evidence of the hereditary transmission of the disease itself, for, of course, if there was a great difference of predisposition between the two races, the fact that all the animals of the Auvergne breed escaped, while all the Devons contracted the disease, was in no way opposed to the view that the spread of the disease among the latter was entirely due to contagion. It ought also to be noted that this happened thirty years ago, before Koch's bacillus had been thought of, and before the days of tuberculin. Did Mr Sanson verify the cause of death in everyone of the Devons and crosses, and how did he know that none of the Auvergne animals were affected? We leave it to the clinicians, who, according to Professor Dewar, are all on his side, to say whether it is in conformity with their experience that tuberculosis is such a deadly disease that it will exterminate a herd of Devons or any other breed in the course of a few years. In the very paper from which we are quoting it is said that tuberculosis among cattle is not a very contagious disease, and yet we
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are asked to believe that in this Auvergne herd it was so contagious that in a few years every Devon and cross-bred animal in the herd became affected! Our incredulity is not with regard to the number of animals that contracted the disease, but \vith regard to its invariably fatal Gourse. We would not like to say with Professor Dewar that tuberculosis is not a very contagious disease, but we would without hesitation assert that even among Devons it is not a very fatal one, and that there has not yet been produced any evidence to show that predisposition to tuberculosis is increased by an attack of the disease, or that the reinforced predisposition is transmitted to the next generation. As to denying the occurrence of predisposition, that is another matter. We never heard of a microbiologist in this or any other country who did not believe that animals of different breeds and families, and even individuals of the same family, exhibit varying degrees of resistance when they become the subjects of tuberculosis, and that the qualities of cells and tissues which underlie this power of resistance are likely to be transmitted by heredity. But, unfortunately, this resistance varies within rather narrow limits, and in the case of our valuable breeds it never amounts to absolute immunity, or even to such a degree of insusceptibility as will enable them to indefinitely withstand the risks of infection when they are housed with other tuberculous animals. There does not appear to be much cogency in citing the resistance of Auvergne cattle to tuberculosis, unless it is meant to suggest that the owners of our pedigree herds of shorthorns, Devons, or Aberdeen-Angus cattle should di~card these, and replace them by some stlmi-wild or mountain breed possessing more marked powers of resistance to tuberculosis. The problem to be solved is to free our existing herds from the disease without sacrificing those desirable qualities which have been built up as characters of the breed by long-continued selection. We may admit that most of our most valued strains of cattle are readily infected with tuberculosis, but those who own them would much rather keep them with this defect than deteriorate the strain by crossing with an inferior breed absolutely immune against the disease, if such a breed could be found. vVe can imagine someone saying that it is not necessary to go outside any of the strains to find animals without this fatal predisposition to tuberculosis, and that by steadily selecting such animals for breeding, and discarding those affected with tuberculosis and all their progeny, it would be possible in the course of a few years to create a herd immune against the disease. It is, of course, not possible to absolutely disprove such a view, but it is easy to show how slender are the foundations on which any such expectations are built. How, in the first place, are we to ascertain which of .the animals in any given herd are devoid of predisposition? Are we to regard present
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freedom from tuberculosis on the part of an animal as evidence of immunity? The supposition is too absurd, for, as has already been mentioned, the tuberculin test if carried out soon after birth would by this method of reasoning prove that almost all animals of the bovine species are immune. Or are we to take freedom of several successive generations as the only evidence of insusceptibility to tuberculosis? That would be an impracticable proposal, for' in most cases we could not obtain the assurance that the progenitors of an animal for even two generations ha~ been free from tuberculosis. In short, it is a great fallacy to assume that even in the same herd it is solely or mainly the varying degrees of predisposition that determine which animals shall become the victims of tuberculosis. As w~1l might it be maintained that it is always the most susceptible ho-;'se that contracts glanders, or credit the animals that do not react to mallein in an outbreak of glanders with immunity against that disease. N or can the predisposition to tuberculosis be detected by a study of conformation, though it appears that there are still to be found clinicians who believe the opposite. Tuberculin has taught us that the narrow chest and other points of conformation, which were once accepted as evidence of a (' phthisical constitution," are of no value whatever as indications of special predisposition to tuberculosis. Such characters are the effects of tuberculosis, not the predisposing cause of that disease, and the most splendid type of conformation is quite compatible with the usual degree of predisposition to tuberculous infection. That these statements are true will not be denied by anyone who has had much experience in the use of tuberculin as a test for tuberculosis in cattle. Professor Dewar finds fault with those who say that if the sources of infection are cut off from healthy animals predisposition may be disregarded, and he remarks that" this may be quite true theoretically, but it is not a very practical way of dealing with the matter." To that it may be replied that if a method is correct in theory it cannot be wrong in practice. \Vhat is the alternative method? To breed only from animals that are free from tuberculosis, and neglect the risk of contagion! That, it may safely be asserted, is wrong in theory, and it would be disastrous in practice. The only sound advice to give to those who are fortunate enough to possess healthy herds is to warn them not to ascribe their present freedom from tuberculosis to absence of predisposition on the part of their animals, or to neglect any reasonable precaution against infection. In like manner, we are entitled to tell those who own herds already affected that the one condition necessary to get rid of the disease is to make a permanent separation between the diseased and the healthy, and that, no matter what the breed or strain may be, a herd may be made and kept free from tuberculosis. ,