Chapter X
Inheritance As A Factor In Disease.—The Process Of Cell Multiplication.—The Sexual Cells Differ From The Other Cells Of The Body.—Infection Of The Ovum.—Intra-Uterine Infection.—The Placenta As A Barrier To Infection.—Variations And Mutations.—The Inheritance Of Susceptibility To Disease.—The Influence Of Alcoholism In The Parents On The Descendants.—The Heredity Of Nervous Diseases.—Transmission Of Disease By The Female Only.—Hemophilia.— The Inheritance Of Malformations.—The Causes Of Malformations.—Maternal Impressions Have No Influence.—Eugenics.
The question of inheritance of disease is closely associated with the study of infection, and the general subject of heredity in its bearing on disease can be considered here. By heredity is understood the transference of similar characteristics from one generation of organisms to another. The formation of the sexual cells is a much more complex process than that of the formation of single differentiated cells, for the properties of all the cells of the body are represented in the sexual cells, to the union of which the heredity transmission of the qualities of the parents is due. In the nucleus of all the cells in the body there is a material called chromatin, which in the process of cell division forms a convoluted thread; this afterwards divides into a number of loops called chromosomes, the number of which are constant for each animal species. In cell division these loops divide longitudinally, one-half of each going to the two new cells which result from the division; each new cell has one-half of all the chromatin contained in the old and also one-half of the cytoplasm or the cell material outside of the nucleus. The process of sexual fertilization consists in the union of the male and female sex cells and an equal blending of the chromatin contained in each (Fig. 22). In the process of formation of the sexual cells a diminution of the number of chromosomes contained in them takes place, but this is preceded by such an intimate intermingling of the chromatin that the sexual cells contain part of all the chromosomes of the undifferentiated cells from which they were formed. The new cell which is formed by the union of the male and female sexual cells and which constitutes a new organism, contains the number of chromosomes characteristic of the species and parts of all the chromatin of the undifferentiated cells of male and female ancestors. As a result of this the most complicated mechanism in nature, it is evident that in a strict sense there can be no heredity of a disease because heredity in the mammal is solely a matter of the chromosomes and these could not convey a parasite. The new organism can, however, quickly become diseased and, by the transference of disease to it and by either parent, there is the appearance of hereditary transmission of disease, though in reality it is not such. The ovum itself can become the site of infection; this, which was first discovered by Pasteur in the eggs of silkworms, takes place not infrequently in the infection of insects with protozoa. In Texas fever the ticks which transmit the disease, after filling with the infected blood, drop off and lay eggs which contain the parasites, and the disease is propagated by the young ticks in whom the parasites have multiplied. The same thing is true in regard to the African relapsing or tick fever, which is also transferred by a tick. In the white diarrhoea of chickens the eggs become infected before they are laid and the young chick is infected before it emerges from the shell. It is highly improbable, and there is no certain evidence for it, that the extremely small amount of material contributed by the male can become infected and bring infection to the new organism. In the cases in which disease of the male parent is transferred to the offspring, it is either by an infection of the female by the male, with transference of the infection from her to the developing organism, or with the male sexual cells there may be a transference to the female of the infectious material and the new organism may be directly infected. No other disease in man is so easily and directly transferred from either parent to offspring as is syphilis, and the disease is extremely malignant for the foetus, usually causing death before the normal period of intra-uterine development is reached.
Fig. 21.—Diagram Showing The Relation Of The Sexual Cells To The Somatic Cells Or Those Of The General Body. The sexual cells are represented to the left of the line at the bottom of diagram and are black. From the fertilized ovum at the top there is a continuous cell development, with differentiation represented in the cell groups of the bottom row. It is seen that the sexual cells are formed directly from the germ cell and contain no admixture from the cells of the body.
The mother gives the protection of a narrow and unchanging environment and food to the new organism which develops within the uterus, and there is always a membranous separation between them. Disease of the mother may affect the foetus in a number of ways. In most cases the membrane of separation is an efficient guard preventing pathogenic organisms reaching the foetus from the mother. In certain cases, however, the guard can be passed. In smallpox, not infrequently, the disease extends from the mother to the foetus, and the child may die of the infection or be born at term with the scars resulting from the disease upon it. Syphilis in the mother in an active stage is practically always extended to the foetus. We have said that in an infectious disease substances of an injurious character are produced by bacteria, and such substances being in solution in the blood of the infected mother can pass through the membranous barrier and may destroy the foetus although the mother recovers from the infection.
Fig. 22.—Diagrammatic Representation Of The Process Of Fertilization. (Boveri.) In the first cell (a) the ovum is shown in process of fertilization by the entering spermatozoon or male sexual element. In the following cells there is shown the increase in amount of the male material and the final intimate commingling in g which precedes the first segmentation. g represents a new organism formed by the union of the male or female cell but differing from either of them.
Living matter is always individual, and this individuality is expressed in slight structural variations from the type of the species as shown in an average of measurements, and also in slight variations in function or the reactions which living tissue shows towards the conditions acting upon it. The anatomical variations are more striking because they can be demonstrated by weight and measure, but the functional variations are equally numerous. Thus, no two brains react in exactly the same way to the impressions received by the sense organs; there are differences in muscular action, differences in digestion; these variations in function are due to variations in the structure of living material which are too minute for our comparatively coarse methods of detection. In the enormous complexity of living matter it is impossible that there should not be minute differences in molecular arrangement and to this such functional variations may be due. Chemistry gives us a number of examples of variations in the reaction of substances which with the same composition differ in the molecular arrangement. Even in so simple a mechanism as a watch there are slight differences in structure which gives to each watch certain individual characteristics, but the type as an instrument constructed for recording time remains. In the fusion of the chromosomes of the male and female sexual cells, to which the hereditary transmission of the ancestral qualities to the new offspring is due, there are differences in the qualities of each, for the individuality of the parents is expressed in the germ cells, and the varying way in which these may fuse gives to the new cell qualities of its own in addition to qualities which come from each ancestor, and from remote ancestors through these. The qualities with which the new organism starts are those which it has received from its ancestors plus its individuality. The fact that the sexual cells are formed from the early formed cells of the new organism which represent all of the qualities of the fertilized ovum or primordial cell, renders it unlikely that the new offspring will contain qualities which the parents have acquired. The question of the inheritance of characteristics which the parents have acquired as the result of the action of environment upon them is one which is still actively investigated by the students of heredity, but the weight of evidence is opposed to this belief.
In the new organism the type of the species is preserved and the variations from the mean to which individuality is due are slight. We are accustomed to regard as variations somewhat greater departures from the species type than is represented in individuality, but there is no sharp dividing line between them.
Very much wider departures from the species type are known as mutations. Such variations and mutations, like individuality, may be expressed in qualities which can be weighed and measured, or in function, and all these can be inherited; certain of them known as dominant characteristics more readily than others, which are known as recessive. If these variations from the type are advantageous, they may be preserved and become the property of the species, and it is in this way that the characteristics of the different races have arisen. Certain of the variations are unfavorable to the race. The varying predisposition to infection which undoubtedly exists and may be inherited represents such a variation. Tuberculosis is an instance of this; for, while the cause of the disease is the tubercle bacillus, there is enormous difference in the resistance of the body to its action in different individuals. The disease is to a considerable extent one of families, but while this is true the degree of the influence exerted by heredity can be greatly overestimated. The disease is so common that in tracing the ancestry of tuberculous patients it is rare to find the disease not represented in the ancestors. A further difficulty is that the environment is also inherited. The child of a tuberculous parent has much better opportunity to acquire the infection than a child without such an environment [page 167]. Other diseases than the infectious seem to be inherited, of which gout is an example. In gout there is an unusual action of the cells of the body which leads to the formation and the retention in the body of substances which are injurious. Here it is not the disease which is inherited, but the variation in structure to which the unusual and injurious action of the cells is due.
While tuberculosis and gout represent instances in which, although the disease itself is not inherited yet the presence of the disease in the ascendants so affects the germinal material that the offspring is more susceptible to these particular diseases, much more common are the cases in which disease in the parents produces a defective offspring, the defect consisting in a general loss of resistance manifested in a variety of ways, but not necessarily repeating the diseased condition of the parent. In these cases the disease in the parents affects all the cells of the body including the germinal cells, and the defective qualities in the germ cells will affect the cells of the offspring which are derived from these. There is a tendency in these cases to the repetition in the offspring of the disease of the parents, because the particular form of the parental disease may have been due to or influenced by variation of structure. One of the best examples of affection of the offspring by diseased conditions of the parents produced by a toxic agent which directly or indirectly affects all the cells of the body is afforded by alcohol when used in excess. Since drunkenness has become a medical rather than a moral question, a great deal of reliable data has accumulated in regard to it as a factor in the heredity of disease. Grotjahn gives the following examples: Six families were investigated in which there were thirty-one children. In all these families the father and grandfather on the father's side were chronic alcoholics, and in certain of the families drunkenness prevailed in the more remote ancestors. The following was the fate of the children: eight died shortly after birth of general weakness, seven died of convulsions in the first month, three were malformed, three were idiotic, three were feeble-minded, three were dwarfs, three were epileptics, two were normal. In a second group of three families there were twenty children. The fathers were drunkards, but their immediate ancestors were free: four children died of general weakness, three of convulsions in the first month, two were feeble-minded, one was a dwarf, one was an epileptic, seven were normal. In a family in which both father and mother and their ancestors were drunkards there were six children: three died of convulsions within six months, one was an idiot, one a dwarf, and one an epileptic. For comparison there were taken from the same station in life ten families in which there was no drunkenness: three children died from general weakness, three from intestinal troubles, two of nervous affection, two were feeble-minded, two were malformed, fifty were normal. Legrain has studied on a larger scale the descendants of two hundred and fifteen families of drunkards in which there were eight hundred and nineteen children. One hundred and forty-five of these were insane, sixty-two were criminals, and one hundred and ninety-seven drunkards. Of course all this cannot be attributed to alcohol alone. There is first to be considered a probable variation in the nervous system which is expressed in the alcoholic habit; second, the environment consisting in poverty, bad associates, etc., which the alcoholic habit brings; third, the alcohol alone. That defective inheritance so frequently takes the form of alcoholism is largely due to the environment. There has never been the opportunity to study on a large scale the effect of the complete deprivation of alcohol from a people living in the environment of modern civilization. There is a possibility, and even probability, that the defective nervous organization which predisposes to alcoholism would seek satisfaction in the use of some other sedative drug. So complex are all the interrelations of the social system that it would be possible to regard alcohol as an agent useful in removing the defective, were it not for its long-enduring action and its effects on the descendants, procreation not being affected by its use.
Diseases of the nervous system are particularly apt to affect the offspring, and often the inherited condition repeats that of the parents. This is due to the fact that most of the nervous diseases depend both upon intrinsic factors which consist in some defective condition of the nervous system representing a variation, and extrinsic factors due to environment or occupation which make the basal condition operative. The definite relation between alcoholism and insanity is due to alcohol acting not as an intrinsic but an extrinsic factor, bringing into effectiveness the hereditary weakness of the nervous system. The influence of heredity in producing insanity is variously estimated at from twenty-six per cent to sixty per cent of all cases. This great difference in the estimation of the hereditary influence is due to the personal equation of the statistician, and the care with which other factors are eliminated. In the more severe form of the hereditary degeneration the same pathological conditions are repeated in the descendants. In certain cases the severity of the condition increases from generation to generation. According to Morel there may be merely what is recognized as a nervous temperament often associated with moral depravity and various excesses in the first generation; in the second, severe neuroses, a tendency to apoplexy and alcoholism; in the third, psychic disturbances, suicidal tendencies and intellectual incapacity; and in the fourth, congenital idiocy, malformations and arrests of development. There are some very definite data with regard to inheritance in the nervous disease known as epilepsy. The essential condition in this consists in attacks of unconsciousness, usually accompanied by a discharge of nerve force shown in convulsions, the attack being often preceded by peculiar sensations of some sort known as the aura. In the most marked forms of the affection heredity plays but little part, owing to the early supervention of imbecility and helplessness, and it is a greater factor in the better classes of society than in the proletariat. In the better classes, owing to the greater care of the cases and the avoidance of exciting causes of the attacks, the disease is better controlled and rarely advances to the extent that it does among the poor. The association of epilepsy and alcoholism is especially dangerous, for a slight amount of alcohol may greatly accentuate the disease. In five hundred and thirty-five children in whose parentage there were sixty-two male and seventy-four female epileptics, twenty-two were born dead, one hundred and ninety-five died from convulsions in infancy, twenty-seven died in infancy from other causes, seventy-eight were epileptics, eleven were insane, thirty-nine were paralyzed, forty-five were hysterical, six had St. Vitus's dance, one hundred and five were ordinarily healthy. That variations in the nervous system which produce more or less unusual mental peculiarities and which do not take the form of nervous disease are inherited, the most superficial consideration shows. A child in its mental characteristics is said to take after one or the other of its parents, certain habits and mental traits are the same, often even the handwriting of a child resembles that of a parent.
In certain cases the inheritance is transmitted by the female alone. This is the case in the hæmophilia, the unfortunate subjects of which are known as bleeders. There is in this a marked tendency to hæmorrhage which depends upon an alteration in the character of the blood which prevents clotting. This, the natural means of stopping bleeding from small wounds, being in abeyance, fatal hæmorrhage may result from pulling a tooth or from an insignificant wound. There is a seeming injustice in the inheritance, for the females do not suffer from the disease although they transmit it, while the males who have the disease cannot even create additional sympathy by transmitting it.
The most obvious inheritance is seen in the case of malformations. These represent wide departures from the type of the species as represented in the form. There is no hard and fast line separating the slight departures from the normal type known as variations and mutations, from the malformations. Certain of the malformations known as monstrosities hardly represent the human type. These are the cases in which the foetus is represented in a formless mass of tissue, or there is absence of development of important parts such as the nervous system or there is more or less extensive duplication of the body. There has always been a great deal of popular interest attached to the malformations owing to the part which maternal impressions are supposed to play in their production. In this, some striking impression made on the pregnant woman is supposed to affect in a definite way the structure of the child. The cases, for instance, in which a woman sees an accident involving a wound or a loss of an arm and the child at birth shows a malformation involving the same part. There is no association between maternal impressions and malformations, although there have been many striking coincidences. All malformations arise during the first six weeks of pregnancy known as the embryonic period, in which the development of the form of the child is taking place, and during which time there is little consciousness of pregnancy. Maternal impressions are usually received at a later period, when the form of the child is complete and it is merely growing. It must be remembered also that there is neither nervous nor vascular connection between the child in the uterus and the mother, the child being from the period of conception an independent entity to which the mother gives nutriment merely. Of course, as has been said, the mother may transmit to the child substances which are injurious, and in certain cases parasites may pass from the mother to the foetus. The same types of malformations which occur in man are also seen in birds, and it would require a more vigorous imagination than is usual to believe that a brooding hen could transmit an impression to an egg and that a headless chick could result from witnessing the sacrifice of an associate. The idea of the importance of maternal impressions in influencing the character of the offspring is a very old one, a well-known instance being the sharp practice of Jacob's using peeled wands to influence the color of his cattle. In regard to coincidences the great number of cases in which strong impressions made on the mind of the pregnant mother without result on the offspring are forgotten. The belief has been productive of great anxiety and even unhappiness during a period which is necessarily a trying one, and should be dismissed as being both theoretically impossible and unsupported by fact.
The malformations are divided anatomically into those characterized, first, by excess formation, second, by deficient formation, third, by abnormal displacement of parts. They are due to intrinsic causes which are in the germ, and which may be due to some unusual conditions in either the male or female germ cell or an imperfect commingling of the germinal material, and to extrinsic causes which physically, as in the nature of a shock or chemically as by the action of a poison, may affect the embryo through the mother. Malformations are made more numerous in chickens by shaking the eggs before brooding. A number of malformations are produced by accidental conditions arising in the environment; for instance, the vascular cord connecting mother and child may become wound around parts constricting them or even cutting them off, and the membrane around the child may become adherent to certain parts and prevent the development of these. The extrinsic causes are more operative the more unfavorable is the environment of the mother. Malformations are more common in illegitimate children than in legitimate and more common in alcoholic mothers; there is an unfavorable environment of poverty in both cases, added to in the latter and usually in the former by the injurious action of the alcohol.
The more extensive malformations have no effect on heredity, because the subjects of them are incapable of procreation. The malformations which arise from the accidents of pregnancy and which are compatible with a perfectly normal germ are in the nature of acquired characteristics and are not inherited. Those malformations, however, which are due to qualities in the germinal material itself are inherited, and certain of them with remarkable persistence. There are instances in which the slight malformation consisting in an excess of fingers or toes has persisted through many generations. It may occasionally lapse in a generation to reappear later. In certain cases, notably in the bleeders, the inheritance is transmitted by the female alone, in other cases by the sexes equally, but there are no cases of transmission by the male line only. It is evident that when the same malformation affects both the male and the female line the hereditary influence is much stronger. A case has been related to me in which most of the inhabitants in a remote mountain valley in Virginia where there has been much intermarriage have one of the joints of the fingers missing. There is a very prevalent idea that in close intermarriage in families variations and malformations often unfortunate for the individual are more common. All experimental evidence obtained by interbreeding of animals shows that close interbreeding is not productive of variation, but that variations existing in the breed become accentuated. Variations either advantageous or disadvantageous for the race or individual may either of them become more prevalent by close intermarriage. It seems, however, to have been shown by the customs of the human race that very close intermarriage is disadvantageous.
Eugenics, which signifies an attempt at the betterment of the race by the avoidance of bad heredity, has within recent years attracted much attention and is of importance. Some of its advocates have become so enthusiastic as to believe that it will be possible to breed men as cattle and ultimately to produce a race ideally perfect. It is true that by careful selection and regulation of marriage certain variations, whether relating to coarse bodily form or to the less obvious changes denoted by function, can be perpetuated and strengthened. That the Semitic race excels in commerce is probably due to the fact that the variation of the brain which affected favorably the mental action conducive to this form of activity, was favorable for the race in the hostile environment in which it was usually placed and transmitted and strengthened by close intermarriage. It is impossible, however, to form a conception of what may be regarded as an ideal type of the human species. The type which might be ideal in a certain environment might not be ideal in another, and environment is probably of equal importance with the material. The eugenics movement has enormously stimulated research into heredity by the methods both of animal experimentation and observation, and study of heredity in man. As in all of the beginning sciences there is not the close inter-relation of observed facts and theory, but there is excess of theory and dearth of facts. Certain considerations, however, seem to be evident. It would seem to be evident that individuals should be healthy and enabled to maintain themselves in the environment in which they are placed, but the qualities which may enable an individual successfully to adapt himself to factory life, or life in the crowds and strong competition of the city, may not be, and probably are not, qualities which are good for the race in general or for his immediate descendants. At present our attempts to influence heredity should be limited to the heredity of disease only. We can certainly say that intermarriage between persons who have tuberculosis or in whose families the disease has prevailed is disadvantageous for the offspring; the same holds true for insanity and for nervous diseases of all sorts, for forms of criminality, for alcoholism, and for those diseases which are long enduring and transmitted by sexual contact such as syphilis and gonorrhoea. It is of importance that the facts bearing on the hereditary transmission of disease should become of general knowledge, in order that the dangers may be known and voluntarily avoided. No measures of preventive medicine are successful which are not supported by a public educated to appreciate their importance, and the same holds true of eugenics. How successful will be public measures leading to the prevention of offspring in the obviously unfit by sterilization of both males and females is uncertain. It is doubtful whether public sentiment at the present time will allow the measure to be thoroughly carried out. Some results in preventing unfit heredity may be attained by the greater extension of asylum life, but the additional burden of this upon the labor of the people would be difficult to bear. At best such measures would only be carried out in the lower class of society.