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.
[Illustration: 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.
[Illustration: 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.