Part 2

Third. There is a growing impression that a good deal of feeblemindedness and insanity are environmental rather than hereditary traits; poverty, malnutrition, and especially syphilis are said to play a considerable rôle in their production. It is unsafe therefore to conclude that the human germ-plasm is as badly contaminated as some pessimists seem to think.

If we turn now more directly to special kinds of human inheritance we shall find a great deal of evidence showing that the same laws of inheritance that hold for animals and for plants apply to man. It would be surprising if this were not the case.

On the other hand, when we scrutinize the pedigrees that have been published to illustrate heredity in man, we shall find many of them very unsatisfactory in two main respects. (1) The number of offspring in a family is usually too small to serve as a sample of the germ-plasm of the parents. (2) Therefore, since recourse must be had to many families for sufficient data, it is essential that the diagnosis of the defects of the parents and of the children is correct. A single mistake may throw the result into confusion. In cases where the defect is structural, a correct classification may be possible, but in other cases, especially where psychological defects are involved, the diagnosis is difficult and the results, in consequence, less certain. Often the best that we can do in the case of man is to try to find the simplest Mendelian formula to which the evidence will fit. If one factor-difference will not suffice, then two must be tried; if two will not do, then three must be tried, etc. Now I need hardly point out that we can explain almost anything if we are allowed enough factors. It is, at best, a dangerous practice, one to be used only with great caution and the conclusion stated as provisional and checked in every possible way.

I propose now to pass in review some characters in man known to be inherited, choosing preferably those that come nearest to the field of pathology, or belonging to it. I shall begin with comparatively simple cases, about which there can be little doubt, and pass to more and more difficult situations. I am taking the risk of reaching an anticlimax, but nevertheless such a procedure will, I hope, serve our purpose this evening if I can point out where the evidence is satisfactory and where it is deficient.

My first illustration of inheritance in man may be said to be a physiological one, mainly because we do not know at present any structural or chemical basis for the reaction.

Color-blindness in man is clearly a case of sex-linked inheritance. It conforms to the general scheme of inheritance in other animals; in Drosophila, for example, we have about sixty mutant characters which show this form of inheritance.

A color-blind man married to a normal woman has only normal daughters and sons; all of the daughters, however, transmit color-blindness to half of their sons, Fig. 6.

Color-blind women are rare, because they can never arise unless a color-blind man marries a woman who is color-blind, or else marries a normal woman who had a color-blind father, or had a mother heterozygous for color-blindness, Fig. 7.

The pedigrees of color-blind families—and they are many—leave little doubt as to the mode of inheritance of this character.

Accepting this evidence as on the whole satisfactory, there is still something more to be said. As is well-known there are many grades of color-blindness. We do not know whether these grades are due to fluctuating (individual) variations—assuming it to be due to one gene: or whether there are several genes that differ in the degree to which they produce the defect. In fact we know now of a good many cases in other animals where there are several mutations of the same gene. For instance, in Drosophila there is a series of ten such multiple allelomorphs for eye colors that range from pure white to deep wine-red. There is still another possible interpretation of the different kinds of color-blindness—one which a priori would seem to be the most probable—namely, that the differences are due to other modifying genes that affect the extent to which the character develops.

While in the great majority of cases, the scheme of color-blindness is that shown by the diagram, we know that occasionally the machinery may be changed to give a somewhat different result. It is possible, for example, that a color-blind man married to a perfectly normal woman may rarely produce a color-blind son. A few years ago such a result would have appeared to upset the entire scheme of sex-linked inheritance, today we understand how such cases may arise through a process that is called non-disjunction, which is best illustrated by numerous cases well worked out in Drosophila.

My second illustration has a more obvious chemical basis. Hemophilia is also sex-linked in inheritance. It is known to be much more common in men than in women, the explanation for this is the same as in the other case. In affected individuals the blood fails to coagulate quickly and the difference in chemical composition of the blood is, in contrast to normal, the inherited character.

One of the most remarkable cases of heredity in man is found in the so-called blood groups. As first definitely shown by Von Dungern and Hirschfeld in 1910, the inheritance of the four blood groups conforms to Mendel’s laws. So consistent is this relation that, as Ottenberg pointed out in 1921, the evidence might be used in certain cases to determine the parentage of the child. Since this statement has recently been disputed by Buchanan, from an entirely wrong interpretation of Mendel’s principles, I should like to point out that on the Mendelian assumption of two pairs of factors, all the known results are fully accounted for. If we represent one pair of genes by A and a and the other pair by B and b, and if we represent an individual with the genetic constitution AaBb mating with another individual of like constitution (AaBb), then each will contain four kinds of germ cells, viz., AB, Ab, Ba, and ab. The sixteen possible combinations formed if any sperm may fertilize any egg are shown in Fig. 8.

These sixteen individuals fall into four groups according to whether they have both A and B, or only A, or only B, or neither A nor B (i.e., ab) in the proportion of 9AB:3A:3B:1ab. These four genetic classes correspond to the four recognized blood types IV, II, III, I, as indicated in the diagram. Now these sixteen kinds of individuals are found in all populations, so far studied, although in somewhat different proportions in different “races.”

It is very simple to tell what the kinds of genetic offspring will be where any one of these sixteen individuals marries any other one. These possibilities are summarized in the following statement taken from Ottenberg:

Unions of I and I give I I II } } I, II II II }

I III } } I, III III III }

Unions of II and III give I, II, III, IV. IV I I, II, III, IV. IV II I, II, III, IV. IV III I, II, III, IV. IV IV I, II, III, IV.

Two actual pedigrees, one of them carried through three generations, will serve to illustrate particular cases, Fig. 9.

From a knowledge of the blood group to which the child belongs it is possible to predict to what groups its parents may have belonged, and in certain cases it is possible to state that an individual of a certain group could not have been the parent of a particular child.

The lower pedigree represents three generations. The grandparents are I and II and I and III, respectively, while the parents are II and III.]

In the transfusion of blood from one individual to another, that is sometimes necessary, it is essential that the blood corpuscles of the donor are not agglutinated by the serum of the recipient. Thus it is a matter of great importance to select a donor that does not bring about such a catastrophe. The simple rules are that individuals belonging to the same blood group (I, II, III, or IV) do not agglutinate each other’s blood, but the blood corpuscles of an individual represented by AA or Aa will be precipitated if the donor contains the agglutinin represented by aa, and conversely the blood corpuscles of an individual represented by BB or Bb will be precipitated if the donor contains the agglutinin represented by bb. Inspection of the diagram will show that group II (with serum bb) precipitates III and IV, and group III (with serum aa) precipitates II and IV. Further the serum of group I (aa bb) precipitates all of the other groups; while the serum of group IV precipitates none of the others.

My fourth illustration has probably in some cases a glandular basis, and in this sense has probably also a quantitative chemical background. Height or stature in man is, in part, an hereditary trait. It is sometimes said that short is dominant to tall, because short parents may have both tall and short children, but tall parents produce only tall children. This is probably an overstatement, or at least a rather loose generalization. Height may be due to long legs, or to a long body, or to a long neck or to time of reaching maturity or to any combination of these; and these differences may themselves be due to independent factors in inheritance. The best that we can do with height at present is to refer it to a multiple factor basis, the actual factors being little understood.

In addition to these differences in stature, all of which we call normal differences, there are certain extreme conditions superimposed on these as a background, in which the endocrine glands probably play an important rôle. While it may well be that many of these cases are caused by tumors of one of the glands, more especially of the pituitary, thyroid, or testis, it is quite possible that there may be actual inherited differences in the size and activity of these glands.

So far as I know there are no thoroughly worked out cases of the inheritance of such differences in man or in mammals, but in the case of certain races of birds I have been able to show both by breeding tests and by castration experiments that glandular differences are inherited according to the Mendelian scheme.

There is a race of fowls known as Campines in which there are two kinds of males, hen-feathered males and cock-feathered males. If the hen-feathered male is castrated, the new feathers that develop are the long feathers of the cock-feathered male, Fig. 10. In another race of fowls, Sebright bantams, only the hen-feathered males are known. If these are castrated, the new feathers that develop are the long feathers characteristic of all other races of poultry, Fig. 11.

If the Sebright male is out-crossed to a hen of another breed in which only cock-feathered males occur, it will be found that all the first generation males are hen-feathered. If these are now bred to their sisters there are produced, in the second generation, three hen-feathered males to one cock-feathered male, showing that the difference between the two races is inherited, Fig. 12.

Now in this case we can perhaps go further. An examination of sections of the testes has shown that in the hen-feathered Sebright male there are certain kinds of cells, called luteal cells, while these are absent in the sections of the testes of normal cocks. These same luteal cells are like those present in the stroma of the ovary of all female birds. If we assume that they make an internal secretion that prevents the development of cock-feathering, both in the normal hen and in hen-feathered cocks, we have a complete explanation of all the facts. This explanation is made more probable by the results of removing the ovary of the hen, when, as Goodale has shown, the spayed hen develops the full male plumage of her breed. Since the luteal cells are present in the hen and in the hen-feathered cock, and are absent in the adult cock-feathered male, it seems not a far-fetched hypothesis to assume that these cells (or their secretions) are those involved.