In discussing Heredity and Sex in 1909, [Footnote: Mendel's Principles of Heredity. Camb. Univ. Press, 1909.] Bateson referred to the effects of castration as evidence that in different types sex may be differently constituted. Castration, he urged, in the male vertebrate on the whole leads merely to the non-appearance of male features, not to the assumption of female characters, while injury or disease of the ovaries may lead to the assumption of male characters by the female. This was supposed to support the view that the male is homozygous in sex, the female heterozygous in Vertebrates: that is to say, the female sex-character and the female secondary sex-characters are entirely wanting in the male. This argument assumes that the secondary characters are essentially of sexual nature without inquiring how they came to be connected with sex, and it ignores the fact that the influence of castration on such characters is a phenomenon entirely beyond the scope of Mendelian principles altogether. The fact that castration does affect, in many cases very profoundly, somatic characters confined to one sex, proves that Mendelian conceptions, however true up to a certain point, are by no means the whole truth about heredity and development. For it is the essence of Mendelism as of Weismannism that not only sex but all other congenital characters are determined in the fertilised ovum or zygote. The meaning of a recessive character in Mendelian terminology is one that is hidden by a dominant character, and both of them are due to factors in the gametes, particularly in the chromosomes of the gametes which come together in fertilisation. For example, in fowls rose comb is dominant over single. A dominant is something present which is absent in the recessive: the rose comb is due to a factor which is absent from the single. The two segregate in the gametes of the hybrid or heterozygote, and if a recessive gamete is fertilised by another recessive gamete the single comb reappears. But castration shows that the antlers of stags and other such characters are not determined in the zygote when the sex is determined, but owe their development, partly at least, to the influence of another part of the body, namely, the testes during the subsequent life of the individual. According to Mendelism the structure and development of each part of the soma is due to the constitution of the chromosomes of the nuclei in that part. The effects of castration show that the development of certain characters is greatly influenced in some way by the presence of the testes in a distant part of the body. The Mendelians used to say it was impossible to believe in the heredity of somatic modifications due to external conditions, because it was impossible to conceive of any means by which such modifications could affect the constitution of the chromosomes in the gametes within the modified body. It would have been just as logical to deny the proved effects of castration, because it was impossible to conceive of any means by which the testes could affect the development of a distant part of the body.
But this is not all. The supposed fact that female secondary characters in Vertebrates are absent in the male is completely disproved for Mammals by the presence of rudimentary mammary glands in the male. It is true that secondary sex-characters are usually positive in the male, while those of the female are apparently negative, but in the case of the mammary glands the opposite is the case. There is no room for doubt that the mammary glands are an essentially female somatic sex-character, not only in their function but in the relation between the periodicity of that function and those of the ovaries and uterus, and it is equally certain from their presence in rudimentary condition in the male that they are not absent from the male constitution.
INFLUENCE OF GONADS DUE TO HORMONES
The existence and the influence of hormones or internal secretions may be said to have been first proved in the case of the testes, for Professor A. A. Berthold [Footnote: 'Transplantation der Hoden,' Archiv. f Anat. u. Phys., 1849.] of Göttingen in 1849 was the first to make the experiment of removing the testicles from cocks and grafting them in another part of the body, and finding that the animals remained male in regard to voice, reproductive instinct, fighting spirit, and growth of comb and wattles. He also drew the conclusion that the results were due to the effect of the testicle upon the blood, and through the blood upon the organism. Little attention was paid to Berthold's experiment at the time. The credit of having been the first to formulate the doctrine of internal secretion is generally given to Claude Bernard. He discovered the glycogenic function of the liver, and proved that in addition to secreting bile, that organ stores up glycogen from the sugar absorbed in the stomach and intestines, and gives it out again as sugar to the blood. In 1855 he maintained that every organ of the body by a process of internal secretion gives up products to the blood. He did not, however, discover the action of such products on other parts or functions of the body. Brown-Séquard, in his address before the Medical Faculty of Paris in 1869, was the first to suggest that glands, with or without ducts, supplied special substances to the blood which were useful or necessary to the normal health, and in 1889 at a meeting of the Société de Biologie he described the experiment he had made upon himself by the injection of testicular extract. This was the commencement of organotherapy. Since that time investigation of the more important organs of internal secretion—namely, the gonads, thyroid, thymus, suprarenals, pituitary, and pineal bodies—has been carried on both by clinical observation and experiment by a great number of physiologists with very striking results, and new hormones have been discovered in the walls of the intestine and other organs.
Here, however, we are more especially concerned with the gonads and other reproductive organs. A great deal of evidence has now been obtained that the influence of the testes and ovaries on secondary sexual characters is due to a hormone formed in the gonads and passing in the blood in the course of the circulation to the organs and tissues which constitute those characters. The fact that transplanted portions of testes in birds (cocks and drakes) are sufficient to maintain the secondary characters in the same condition as in normal individuals shows that the nexus between the primary and somatic organs is of a liquid chemical nature and not anatomical, through the nervous system for example. Many physiologists in recent years have maintained that the testicular hormone is not derived from the male germ-cells or spermatocytes, but from certain cells between the spermatic tubuli which are known as interstitial cells, or collectively as the interstitial gland.
The views of Ancel and Bouin, [Footnote: C. R. Soc. Biol., iv.] published in 1903, may be described in large part as theory. They state that the interstitial cells appear in the male embryo before the gametocytes present distinctive sex-characters. They conclude that the interstitial cells supply a nutritive material (hormone?), which has an effect on the sexual orientation of the primitive generative cells. In addition to this function, the interstitial cells by their hormone also give the sexual character to the soma. When castration is carried out at birth the male somatic characters do not entirely disappear, because the hormone of the interstitial cells has acted during intrauterine life. The functional independence between the interstitial cells and the seminal tubules is shown by the fact that if the vasa deferentia are closed the seminal gland (i.e. tubules) degenerates while the interstitial cells do not. In the embryo the interstitial gland is large, in the adult proportionately small.
There is complete disagreement between the results of Ancel and Bouin on the one hand, and those of Shattock and Seligmann on the other, with regard to the effects of ligature of the vasa deferentia. The latter authors, as mentioned above, found that after ligature not only the somatic characters but the testis itself developed normally. The experiments were performed on Herdwick sheep and domestic fowls. They state that on examination the testes were found to be normally developed, and spermatogenesis was in progress. The experiments of Ancel and Bouin were carried out on rabbits seven to eight weeks old, and consisted in removing one testis, and ligaturing the vas deferens of the other. About six months after the operation the testis left in situ was smaller, the seminal tubules contained few spermatogonia, though Sertoli's cells (cells on the walls of the tubules to which the true spermatic cells are attached) were unchanged; while the interstitial cells were enormously developed, by compensatory hypertrophy in consequence of the removal of the other testis. At the same time the male instincts and the other generative organs were unchanged. In a few cases, however, Ancel and Bouin observed atrophy of the interstitial cells as well as the spermatic cells. They believe this is due to the nerves supplying the testis being included in the ligature. This is rather a surprising conclusion in view of the fact that testicular grafts show active spermatogenesis. It is difficult to understand why nerve connection should be necessary for the interstitial cells and not for the spermatic, and, moreover, if the interstitial cells are really the source of the hormone on which the somatic characters depend, they must be acting in the grafts in which the nerve connections have been all severed.
The facts concerning cryptorchidism, that is to say, failure of the descent of the testes in Mammals, seem to show that the hormone of the testis is not derived from semen or spermatogenesis, for in the testes which have remained in the abdomen there is no spermatogenesis, while the interstitial cells are present, and the animals in some cases exhibit normal or even excessive sexual instinct, and all the male characteristics are well marked. It may be remarked, however, in criticism of this conclusion that the descent of the testes being itself a somatic sexual character of the male, its failure when the interstitial cells are normal and the spermatic cells defective, would rather tend to prove that the defect of the latter is itself the cause of cryptorchidism.
Many investigators have found that the Röntgen rays destroy the spermatic cells of the testis in Mammals, leaving the cells of Sertoli, the interstitial tissue, nerves, and vessels uninjured. Tandler and Gross [Footnote: Wiener klinische Wochenschrift, 1907.] found that the antlers of roebuck were not affected after the testes had been submitted to the action of the rays, showing that the interstitial cells were sufficient to maintain the normal condition of the antlers. Simmonds, [Footnote: Fortschr. a. d. G. d. Röntgenstr., xiv., 1909-10.] however, found that isolated seminal tubules remained, and regeneration took place, and concludes that both spermatic cells and interstitial cells take part in producing the testis hormone. The conclusions of two other investigators have an important bearing on this question—namely, that of Miss Boring [Footnote: Biol. Bull., xxiii. 1912.] that there is no interstitial tissue in the bird's testis, and that of Miss Lane-Claypon, [Footnote: Proc. Roy. Soc., 1905] that the interstitial cells of the ovary arise from the germinal epithelium, and are perfectly equipotential with those which form the ova and Graafian follicles. It seems possible, although no such suggestion has been made, that the interstitial cells might either normally or exceptionally give rise to ova and spermatocytes. The observations of Seligmann and Shattock on the relation of spermatogenesis to the development of nuptial plumage in drakes probably receive their explanation from the above facts. Spermatogenesis is not the only source of the testicular hormone: changes in the secretory activity of the interstitial cells or spermatocytes are sufficient to account for periodic development of somatic sex-characters, and the same reasoning applies to the antlers of stags.