Some possible bearings of genetics on pathology

by Thomas Hunt Morgan

Fig. 14. Diagram showing inheritance of a sex-linked recessive lethal (“tumor”) factor in Drosophila melanogaster. Here, in the center of the diagram, the sex-chromosome that carries the lethal factor is represented by the black rod. A female with the tumor-factor, normal wings and red eyes, in one of her sex-chromosomes and with the factors for yellow wings and eosin eyes in the other is bred in each generation to a male with yellow wings and eosin eyes. In the next generation there are twice as many daughters as sons, since all the sons that carry the black chromosome die. The half of the daughters (i.e., those not yellow eosin) that carry the black chromosome repeat the same history. The linkage of yellow and eosin enables one to pick out in each generation those daughters that carry the tumor-factor.

All males that get their single X with this tumor-gene will die; therefore, since no adult males carry it, normal males must be used for mating in each generation. They are mated to females that are heterozygous for the chromosome carrying the tumor genes. Such matings as I have said always give two daughters to one son. But since half the daughters are normal and half carry the gene for tumor it is desirable to be able to pick out the latter from the stock. Therefore we have made use of a trick we call “marking the chromosome,” which means that we use a male whose sex chromosome carries a known gene near the tumor locus. By using this type of male in successive generations we get two types of daughters: one type like their surviving brothers in eye color that do not carry the tumor-gene and the other daughter with normal eyes that carries it. We use only the latter to continue the stock, but we could eliminate the tumor from the stock at once by using the other kind of daughters.

Curiously enough the tumor no longer appears in the inbred stock but reappears again on out-breeding. Nevertheless the sex-ratio in the inbred stock continues as before, and since the missing males are those with red eyes we know that the tumor-gene is still present and doing its deadly work—only now the young male larvæ die even before they reach the age at which the tumor is due to appear.

So far I have spoken of heredity as though that term had become synonymous with Mendelian heredity. Those of as who are at work on Mendelian inheritance are often criticized as too narrow. It is said that we do not recognize that any other kind of inheritance takes place. I do not think the criticism is quite fair, because, in the first place, the very great number of variations studied has been shown to conform to the Mendelian principles or at least to be capable of such interpretation. There are, however, a few exceptional cases. In certain albino plants it has been shown that the inheritance of albinism can be traced to the behavior of the chlorophyll bodies in the cytoplasm. The chlorophyll bodies are known to divide and to be distributed to the two daughter cells at each division independently of the nuclear division and of the maturation process in the egg.

Why, then, it is asked, may not there be present in the cytoplasm of the cell other self-perpetuating bodies that are responsible for certain kinds of inheritance? Why not go further and ask, why, since the cytoplasm appears to be handed down from cell to cell, may it not furnish also a different medium for inheritance of characters? Theoretically such an argument is logical. No student of Mendelism would I think deny such a possibility. But, as a matter of fact, it is not going too far to say that, at present, there is little evidence that such inheritance takes place, except in a few special cases, like that of the chlorophyll bodies. It is safe, I think, to say that if cytoplasmic inheritance played any important rôle in heredity in the higher animals and plants, we should expect, by now, to have found many cases of it. None are known to us.

Whether Mendel’s laws of heredity apply to unicellular animals, to bacteria and to similar types, in which the mechanism for this type of inheritance has not been shown to exist, can not be affirmed or denied from the evidence at hand.

There are at present three outstanding cases in the higher animals, in which an induced variation is said to be inherited afterwards. These cases are of great interest to pathology. We can not afford to pass them over. First, there is Brown-Sequard’s claim that injuries to the nerve cord or to the cervical or sciatic nerves of guinea pigs produce effects that are transmitted.

Second, there are the cases of the inherited effects caused by alcohol in guinea pigs discovered by Stockard.

Third, there is Guyer’s evidence that an effect on the eye, caused by foreign serum, is transmitted.