THE MAMMARY OR MILK GLANDS

The milk glands in Mammals constitute one of the most remarkable of secondary sexual characters. Except in their functional relations to the primary organs, the ovaries, and to the uterus, there is nothing sexual about them. They are parts of the skin, being nothing more or less than enormous enlargements of dermal glands, either sebaceous or sudoriparous. Uterine and mammary functions are generally regarded as essentially female characteristics, and are included in the popular idea of the sex of woman. Scientifically, of course, they are not at all necessary or universal features of the female sex, but are peculiar to the mammalian class of Vertebrates in which they have been evolved. Milk glands, then, are somatic sex-characters common to a whole class, instead of being restricted to a family like the antlers in Cervidae. There is not the slightest trace or rudiment of them in other classes of Vertebrates, such as Birds or Reptiles. They are not actually sexual in their nature, since their function is to supply food for the young, not to play a part in the relations of the sexes. What is sexual about them is—firstly, that they are normally fully developed only in the female, rudimentary in the male; secondly, that their periodical development and functional activity depends on the changes which take place in the ovary and uterus. Many investigators have endeavoured to discover the nature of the nexus between the latter organs and the milk glands.

That this nexus is of the nature of a hormone is generally agreed, and may be regarded as having been proved in 1874 when Goltz and Ewald [Footnote: Pfluegers Archiv, ix., 1874.] removed the whole of the lumbo-sacral portion of the spinal cord of a bitch and found that the mammae in the animal developed and enlarged in the usual way during pregnancy and secreted milk normally after parturition. Ribbert [Footnote: Fortschritte der Medicin, Bd. 7.] in 1898 transplanted a milk gland of a guinea-pig to the neighbourhood of the ear, and found that its development and function during pregnancy and at parturition were unaffected. The effective stimulus, therefore, is not conveyed through the nervous system, but must be a chemical stimulus passing through the vascular system.

Physiologists, however, are not equally in agreement concerning the source of the hormone which regulates lactation. Starling and Miss Lane-Claypon concluded from their experiments on rabbits that the hormone originated in the foetuses themselves within the pregnant uterus. In virgin rabbits it is difficult to find the milk glands at all. When found the nipple is minute and sections through it show the gland to consist of only a few ducts a few millimetres in length. Five days after impregnation the gland is about 2 cm. in diameter. Nine days after impregnation the glands have grown so much that the whole inner surface of the skin of the abdomen is covered with a thin layer of gland tissue. In six cases by injecting subcutaneously extracts of foetus tissue Starling and Lane-Claypon obtained a certain amount of growth of the milk glands. The hormone in the case of the pregnant rabbit is of course acting continuously for the whole period of pregnancy, while the artificial injection took place only once in twenty-four hours, and the amount of hormone it contained may have been absorbed in a very short time. The amount of growth obtained experimentally in five weeks was less than that occurring in pregnancy in nine days. Extracts of uterus, placenta, or ovary produced no growth, although the ovaries used were taken from rabbits in the middle of pregnancy. In one experiment ovaries from a pregnant rabbit were implanted into the peritoneum of a non-pregnant rabbit, but on post-mortem examination of the latter eleven days later the implanted ovaries were found to be necrosed and no proliferation of milk gland had taken place.

The conclusions of Starling and Lane-Claypon were confirmed by Foa, [Footnote: Archivo d. Fisiologia, v., 1909.] and by Biedl and Koenigstein, [Footnote: Zeitschrift f. exp. Path. und Therap., 1910.] Foa states that extracts of foetuses of cows produced swelling of the mammae in a virgin rabbit.

O'Donoghue, however, concludes from a study of the Marsupial Dasyurus that the stimulus which upon the milk glands proceeds from the corpora lutea in the ovary. In this animal changes in the pouch occur in pregnancy, which are doubtless also due to hormone stimulation, but which we will not consider here. The most important evidence in O'Donoghue's paper [Footnote: Quart. Journ. Mic. Sci., lvii., 1911-12.] is that development of the milk glands takes place after ovulation not succeeded by pregnancy; that is to say, when corpora lutea are formed but no fertilised ova or foetus are present in the uterus. In one case eighteen days after heat, the milk gland was in a condition resembling that found in the stages twenty-four and thirty-six hours after parturition. In another specimen, twenty-one days after heat, the milk glands were still more advanced, with distended alveoli and enlarged ducts. The alveoli contained a secretion which was almost certainly milk, O'Donoghue states that the entire series of growth changes in these animals up to twenty-one days after heat in identical with that which occurs in normally pregnant animals.

O'Donoghue's conclusion is in agreement with that of Basch,[Footnote: Monatesschr. f. Kinderh. V., No. ix., Dec. 1909.] who states that implantation of the, ovaries from a pregnant bitch under the skin of the back of a one-year-old bitch that was not pregnant was followed by proliferation of the mammary glands of the latter. After six weeks the glands were considerably enlarged, and after eight weeks they were caused to secrete milk by the injection of extract of the placenta. It has to be remembered, however, that the milk glands undergo considerable growth, especially in the human species, at puberty and at every menstruation, or at oestrus in animals, which correspond to menstruation. In these cases there is no question of any influence of the foetus, and experiment has shown that if the ovaries are removed before puberty, the milk glands nor the uterus undergo the normal development and menstruation does not occur. According to Marshall to Jolly [Footnote: Quart. Journ. Exp. Phys., i. and ii., 1906.] the symptoms of oestrus in castrated bitches were found to result from the implantation of ovaries from other individuals in the condition of oestrus.

Before considering further the question of the corpora lutea as organs of internal secretion, we may briefly refer to the origin and structure of these bodies and of other parts of the mammalian ovary. The mature follicle containing the ovum differs from that of other Vertebrates in the fact that it is not completely filled by the ovum and the follicular cells surrounding it, but there is a cell-free space of large size into which the ovum covered by follicular cells projects. In the wall of the follicle two layers are distinguished, the theca externa, which is more fibrous, and the theca interna, which is more cellular. In the connective tissue stroma of the ovary between the follicles are scattered, or in some cases aggregated, epithelioid cells known as the interstitial cells, and it is stated that the cells of the theca interna are exactly similar to the interstitial cells. According to Limon [Footnote: Arch. d'Anat. micr., v., 1902.] and Wallart [Footnote: Arch. f. Gynock, vi. 271.] the interstitial cells are actually derived from those of the theca interna of the follicles. Numbers of ova die without reaching maturity, the follicular cells degenerate, and the follicle becomes filled with the cells of the theca interna, which have a resemblance to those of the true corpus luteum. These degenerate follicles have been termed spurious corpora lutea, or atretic vesicles. The interstitial cells are the remains of these atretic vesicles. The true corpora lutea arise from follicles in which the ova have become mature and from which they have escaped through the surface of the ovary. As a result of the escape of the ovum and the contents of the cell-free space, the follicle contracts and the follicular (so-called granulosa) cells secrete a yellow substance, lutein, and enlarge. Buds from the theca interna invade the follicle and form the connective tissue of the corpus luteum.

Somewhat similar processes take place in the ovaries of Teleostean fishes, as I know from my own observations, but no corpora lutea are formed in these, although the degenerating follicles in course of absorption correspond to corpora lutea. The spawning of Fishes, usually annual, corresponds to ovulation in Mammals, and in the ovary after spawning the numerous collapsed follicles containing the follicular cells may be seen in all stages of absorption. [Footnote: Cunningham, 'Ovaries of Teleosteans.' Quart. Journ. Mic. Sci., vol. xl. pt. 1., 1897.] At other times of the year sections of the ovary show here and there ova which after developing to a certain stage die and undergo absorption with their follicles.

In the higher Mammals (Eutheria) the corpora lutea show a special relation in their development to the occurrence of pregnancy, that is to say, they have a different history when ovulation is followed by pregnancy to that which they have when the ova, from the escape of which they arise, are not fertilised. When fertilisation occurs the corpus luteum increases in size during the first part of the period of gestation (four months, or nearly a half of the whole period in the human species). It then remains without much change till parturition, after which it shrinks and is absorbed. When pregnancy does not occur the corpus luteum is formed, but begins to diminish within ten or twelve days in the human species and is then gradually absorbed. According to O'Donoghue, in the Marsupial Dasyurus there seems to be no difference either in the development of the milk glands or of the corpora lutea between the pregnant and the non-pregnant animal. Sandes [Footnote: Proc. Lin. Soc., New South Wales, 1903.] showed that in the same species the corpora lutea persisted not only during the whole of pregnancy, which Professor J. P. Hill [Footnote: Anat. Anz., xviii., 1900.] estimates at a little over eight days, but during the greater part of the period of lactation, which according to the same authority is about four months. In the specimens of Dasyurus described by O'Donoghue, in which the milk glands developed after ovulation without ensuing pregnancy, normally developed corpora lutea were present in the ovary. Of the five females which he mentions, the first three, one with unfertilised ova in the uteri, two five and six days after heat, could not have been pregnant, but the other two killed eighteen and twenty-one days after heat might, since pregnancy lasts only eight days, have been pregnant, the young having died at parturition or before. To make certain on this point it would have been necessary to examine the ovaries and milk glands of females which had been kept separate from a male the whole time. There is no doubt, however, about the development of the milk glands in the first three specimens, which were certainly not pregnant.

It is difficult to reconcile entirely the evidence described by O'Donoghue from Dasyurus, with that obtained from higher Mammals, although on the whole there is reason to conclude that the corpora lutea have an important influence on the development of the milk glands. According to Lane-Claypon and Starling, if the ovaries and uteri are removed from a pregnant rabbit before the fourteenth day the development of the mammary gland ceases, retrogression takes place, and no milk appears in the gland. If, on the other hand, the operation be performed after the fourteenth day, milk appears within two days after the operation. It is to be concluded from this that the cause of secretion of milk is the withdrawal of a stimulus proceeding from ovary or uterus. But O'Donoghue believes that milk is secreted in Dasyurus when no pregnancy has occurred. Ancel and Bouin [Footnote: C. R. Soc. de Biol., t. lxvii., 1909.] have shown that the growth of the mammary glands was produced in rabbits by the artificial rupture of egg follicles and consequent production of corpora lutea: the growth of the glands continued up to the fourteenth day, after which regression set in. This shows that the development of the milk glands in rabbits is due to the corpora lutea. On the other hand, Lane-Claypon and Starling state that in rabbits the corpora lutea diminish after the first half of pregnancy, while the growth of the milk glands is many times greater during the second half than during the first half of the period, and during the second half the ovaries may be removed entirely without interfering with the course of pregnancy or the normal development of the milk glands. It is evident, therefore, that in rabbits, whatever influence the corpora lutea may have in the first half of pregnancy, they have none in the second half, and that at this period the essential hormone proceeds from the developing foetus or foetal placenta. Again, if it is the withdrawal of a hormone stimulus which changes the milk gland from growth to secretion, it cannot be the corpora lutea which are exclusively concerned even in Dasyurus, for they persist during lactation, while secretion begins shortly after parturition.

Gustav Born suggested, and Fraenkel tested the suggestion experimentally, that the corpus luteum of pregnancy is a gland of internal secretion whose function is to cause the attachment of the ovum in the uterus and the normal development of uterus and placenta. Fraenkel found that removal of both ovaries in rabbits between the first and sixth days after fertilisation prevented pregnancy, and that the same result followed if the corpora lutea were merely destroyed in situ by galvano-cautery. Either process carried out between the eighth and twentieth days of pregnancy causes abortion.

Lane-Claypon and Starling also found that removal of both ovaries in the rabbit before the fifteenth day was apt to cause abortion, but at a later stage the same operation could be performed without interfering with the course of pregnancy. According to these authors numberless instances prove that in women double ovariotomy does not necessarily interfere with the course of pregnancy or the development of the milk glands. Parturition may take place and be followed by normal lactation. This shows that a hormone from the corpora lutea is not necessary either to the uterus or the milk glands, at any rate in the last third of pregnancy, though of course this does not prove that such a hormone is not necessary for the earlier stages both of pregnancy and growth of the milk glands.

The results of Steinach, if confirmed, would prove conclusively that the ovaries and testes produce hormones which determine the development of all the sexual characters, not merely physical but psychical. He adopts the view that the interstitial cells or gland are the source of the active hormone. He claims by transplantation of the gonads in young rats and guinea-pigs to have feminised males and masculised females. The females are smaller, and hare finer, softer hair than the males. The testes were removed and ovaries implanted in young males. The animals so treated grew less than the merely castrated specimens, and therefore when full-grown resembled females in size. In the young state both sexes have fine, soft hair, the feminised males had the same character, like the normal females. They also developed teats and milk glands like the females, and were sought and treated as females by the normal males. When the implanted ovaries are able to resist the influence of their new surroundings, the female interstitial gland, which Steinach calls the puberty gland, develops so much that an intensification of the female character takes place: the animals are smaller than normal females, the milk glands develop and secrete milk, which can be easily pressed out, and if young are given to them they suckle them and show all the maternal instincts.

Why the ovary in normal circumstances only when in the gravid condition calls forth this perfection of femaleness is to be shown in a later publication. By acting with Roentgen rays on the region where the ovaries lie, Steinach and his colleague Holzknecht brought about all the symptoms of pregnancy, development of teats and milk glands, secretion of milk, and great growth of the uterus in all its layers.

Masculising of females was much more difficult than feminising of males because the testicular tissue was less resistent, and could not be grafted so easily. When it succeeded, however, degeneration of the seminal tubules took place, with increase of the interstitial or Leydig's cells. The vaginal opening in rats disappeared, partly or completely. The sexual instincts became male, the animals recognised a female in heat from one that was not, and attempted to copulate.

Steinach considers that he has proved from results that sex is not fixed or predetermined but dependent on the puberty gland. By sex here he obviously means the instincts and somatic characters, for sex in the first instance, as we have already pointed out, means the difference between ovary and testis, between ova and spermatozoa. It is difficult to accept all Steinach's results without confirmation, especially those which show that the feminised male is more female than the normal female. Such a conclusion inevitably suggests that the investigator is proving too much.

The subject of the influence of hormones from the gonads is mentioned, but not fully discussed, in a volume by Dr. Jacques Loeb, entitles The Organism as a Whole. [Footnote: Putnam's Sons, 1916.] Loeb entirely omits the problem of the origin of somatic sex-characters, and fails to perceive that the fact that such characters are dependent to a marked degree on hormones derived from the gonads, together with their relation to definite habits and functions connected with the behaviour of the sexes to each other, is proof are these characters are not gametogenic, but were originally due to external stimulation of particular parts of the soma.



CHAPTER IV

Origin Of Somatic Sex-Characters In Evolution

In his Mendel's Principles of Heredity, 1909, Bateson does not discuss the nature of somatic sex-characters in general, but appears to regard them as essential sex-features, as male or female respectively. As mentioned above, he argues from the fact that injury or disease of the ovaries may lead to the development of male characters in the female, that the female is heterozygous for sex, and from the supposed fact that castration of the male leads merely to the non-appearance of male somatic characters, that the female sex-factor is wanting in the male. He does not distinguish somatic sex-characters from primary sex-factors, and discusses certain cases of heredity limited by sex as though they were examples of the same kind of phenomenon as somatic sex-characters in general. One of these cases is the crossing by Professor T. B. Wood of a breed of sheep horned in both sexes with another hornless in both sexes. In the F1 generation the males were horned, the females hornless. Here, with regard to the horned character, both sexes were of the same genetic composition, i.e. heterozygous, or if we represent the possession of horns by H, and their absence by h, both sexes were Hh. Thus Hh[male] was horned and Hh[female] was hornless, or, as Bateson expresses it, the horned character was dominant in males, recessive in females. Bateson offers no explanation of this, but it obviously suggests that some trace of the original dimorphism of the sheep in this character was retained in both horned and hornless breeds. We may suppose that the factor for horns had disappeared entirely from the hornless sheep by a mutation, but in the horned breed another mutation had been a weakening of the influence of the sexual hormones on the development of the character, which, as in all such cases, is really inherited in both sexes. In the F1, when the horned character in the female is only inherited from one side, the hereditary tendency is not enough to overcome the influence of the absence of the testis hormone and presence of the ovarian hormone, and so the horns do not develop. The Mendelian merely sees a relation of the character to sex, but overlooks entirely the question of the dimorphism in the original species from which the domesticated breeds are descended. Similarly, with regard to cattle where it has been found that hornlessness is dominant or nearly so in both sexes, no reference is made to the opposite fact that wild cattle have horns in both sexes and are not dimorphic in this character.

Bateson proceeds to consider colour-blindness as though its heredity were of similar kind. He refers to it as a male character latent in the female, remarks that we should expect that disease or removal of the ovaries might lead to the occasional appearance of colour-blindness in females. He also discusses the case of Abraxas grossulariata and its variety lacticolor, and other cases of sex-linked heredity, apparently with the idea that all such cases are similar to those of sexual dimorphism. A. lacticolor occurs in nature only in the female sex, and when bred with grossulariata [male] produces [male]'s and [female]'s all grossulariata, these of course being heterozygous. When the F1 grossulariata [male] was bred with the wild lacticolor [female] it produced both forms in both sexes, and thus lacticolor [male] was obtained for the first time. When this lacticolor [male] was bred with F1 grossulariata[female] it produced all the [male]'s grossulariata and all the [female]'s lacticolor. Bateson's explanation is that the female, according to the Mendelian theory of sex, is heterozygous in sex, the male homozygous and recessive, and that lacticolor is linked with the female sex-character, grossulariata being repelled by that character. Thus we have, the lacticolor character being recessive,

lact. male, LL male male x F, gross. female, GL female male Gametes L male + L male x G male + L female GL male male LL male female gross. male lact. female

It will be seen that although in the progeny of this mating all the grossulariata were males and all the lacticolor females, yet this case is by no means similar to that of sexual dimorphism in which the characters are normally always confined to the same sex. For the lacticolor character in the parent was in the male, while in the offspring it was in the female. We cannot say here that in the theoretical factors which are supposed to represent what happens, the lacticolor character is coupled with the female sex-factor, for we find it with the male sex-character in the lacticolor [male]. It is so coupled only in the heterozygous grossulariata [female], and at the same time the grossulariata character is repelled.

According to Doncaster [Footnote: Determination of Sex, Camb. Univ. Press, 1914.] sex-limited, or as it is now proposed to call it sex-linked, transmission in this case means that the female grossulariata transmits the character to all her male offspring and to none of the female, while a heterozygous male grossulariata mated with lacticolor female transmits the character equally to both sexes: that is to say, the heredity is completely sex-limited in the female but not at all in the male. This is evidence that the female produces two kinds of eggs, one male producing and the other female producing.

With regard to the ordinary form of colour-blindness, Bateson's first explanation was that it was like the horns in the cross-bred sheep, dominant in males, recessive in females. About 4 per cent. of males in European countries are colour-blind, but less than 1/2 per cent. of females. Affected males may transmit the defect to their sons but not to their daughters: but daughters of affected persons transmit the defect frequently to their sons. Bateson gives [Footnote: Mendel's Principles of Heredity, 1909.] a scheme of the transmission, but corrects this in a note stating that colour-blindness does not descend from father to son, unless the defect was introduced by the normal sighted mother also, i.e. was carried by her as a recessive. The fact that unaffected males do not transmit the defect shows, according to Bateson, that it is due to the addition of a factor to the normal, not to omission of a factor.

According to later researches as quoted by Doncaster, colour-blindness is due to the loss of some factor which is present in the normal individual. The normal male is heterozygous for this normal factor. If we denote the presence of the normal factor by N and its absence or recessive by n, then the male is Nn, while the female is homozygous or NN. But in addition to this it is the male in this case which is heterozygous for sex, and n goes to the male-producing sperms, N to the female-producing. Thus in the mating of normal man with normal woman the transmission is as follows:—

Nn (male) x NN (female) Gametes n (male) + N (female) x N + N

n (male) + N N (female) + N Nn (male) NN (female)

That is all offspring normal, but the males again heterozygous.

An affected male has the constitution nn, and if he marries a normal woman the descent is as follows:—

nn (male) x NN (female) Gametes n (male) + n (female) x N + N

n (male) + N N (female) + N nN (male) nN (female)

When a normal male is mated with a heterozygous nN female we get

nN (male) x nN (female) Gametes n (male) + N (female) x n + N nn (male) nN (male) nN (female) NN (female)

that is, half the sons are normal and half colour-blind, while half the females are homozygous and normal, and the other half heterozygous and normal.

T. H. Morgan [Footnote: A Critique of the Theory of Evolution.] has observed a number of cases of sex-linked inheritance in the mutations which occurred in his cultures of Drosophila. The eye of the wild original fly is red, one of the mutants has a white eye, i.e. the red colour and its factor are absent. When a white-eyed male is mated to a red-eyed female all the offspring have red eyes. If these are bred inter se, there are, as in ordinary Mendelian cases, three red-eyed to one white-eyed in the F2 generation, but white eyes occur only in the males, in other wards half the males are white-eyed. On the other hand, when a white-eyed female is mated to a red-eyed male all the daughters have red eyes, and all the sons white eyes. This has been termed crisscross inheritance. If these are bred together the result in F2 is equal numbers of red-eyed and white-eyed females, and equal numbers of red-eyed and white-eyed males. The ration of dominant to recessive is 2 to 2 instead of the usual Mendelian ration of 3 to 1.

According to Morgan the interpretation is as follows: In the nucleus of the female gametocytes there are two X chromosomes related to sex, in those of the male there is one X chromosome and one Y chromosome of slightly different shape. The factor for red eye occurs in the sex-chromosomes, that is to say, according to this theory, the sex-chromosome does not merely determine sex but carries other factors as well, and this fact is the explanation of sex-linked inheritance. The factor for red eye then is present in both X chromosomes of the wild female, absent from both X and Y chromosomes of the white-eyed male. The gametes of the female each carry one X red chromosome, of those of the male half carry an X white chromosome, and half the Y white chromosome. The fertilised female ova therefore carry an X red chromosome + an X white chromosome, the male producing ova one X red chromosome and one Y white chromosome. They are all therefore red-eyed, but heterozygous—that is, the red eye is due to one red-eye factor, not two. When the F1 are bred together, half the female gametes carry one X red chromosome, the other half one X white chromosome; half the male gametes carry one X red chromosome, the other half one Y white chromosome. The fertilisations are therefore one X red X red, one X red X white, one X red Y white, and one X white Y white. These last are the white-eyed males. The two different crosses are represented diagrammatically below, the dark rod representing the X red chromosome, the clear rod the X white chromosome, and the bent clear rod the Y white chromosome.

According to Morgan, the heredity of colour-blindness in man is to be explained exactly in the same way as that of white eye in Drosophila. A colour-blind man married to a normal (homozygous) woman transmits the peculiarity to half his grandsons and to none of his grand-daughters. Colour-blind women are rare, but in the few cases known where such women have married normal husbands the defect has appeared only in the sons, as in the second of the diagrams below.

Parents Red-eyed male White-eyed female XR XR x XW YW

F1 Red-eyed male Red-eyed female XR XW XR YW

F2 Red-eyed male Red-eyed male Red-eyed female White-eyed female XR XR XW XR XR YW XW YW Homozygous. Heterozygous. Heterozygous. Homozygous.

White-eyed male Red-eyed female XW XW x XR YW

F1 Red-eyed male White-eyed female XW XR XW YW

F2 White-eyed male Red-eyed male White-eyed female Red-eyed female XW XW XR XW XW YW XR YW Homozygous. Heterozygous. Homozygous. Heterozygous.

It must be explained that according to this theory the normal male is always heterozygous, because the Y chromosome never carries any other factor except that for sex; it is thus of no more importance than the absence of an X chromosome which occurs in those cases where the male has one sex-chromosome and the female two. According to the researches of von Winiwarter [Footnote: 'Spermatogenese humaine,' Arch. de Biol., xxvii., 1912.] on spermatogenesis in man, the latter is actually the case in the human species. This investigator found that there were 48 chromosomes in the female cell, 47 in the male; after the reduction divisions the unfertilised ova had 24 chromosomes, half the spermatids 24 and half 23, so that sex is determined in man by the spermatozoon.

Morgan believes that the heredity of haemophilia (the constitutional defect which prevents the spontaneous cessation of bleeding) follows the same scheme, and also at least some forms of stationary night-blindness— that is, the inability to see in twilight.

We may mention a few other in animals, referring the reader for a fuller account to the works cited. One example in the barred character of the feathers in the breed of fowls called Plymouth Rock. In this the female is heterozygous for sex as in Abraxas grossulariata, and the barred character is sex-linked. When a barred hen is crossed with an unbarred cock all the male offspring are barred, all the females plain. On the other hand, if a barred cock is crossed with an unbarred hen, the barred character appears in all the offspring, both and females. The female thus transmits the character only to her sons. If we represent the barred character by B, and its absence by b, we can represent the heredity as follows:—

BARRED FEMALE WITH UNBARRED MALE

B female b male X b male b male

Bb male bb female

Barred male. Unbarred female. Heterozygous. Homozygous.

B male B male X b female b male

B male b female b male b male

Barred female. Barred male. Heterozygous. Heterozygous.]

This case is thus exactly similar to that of Abraxas grossulariata and A. lacticolor. The barred character like grossulariata is dominant, the unbarred recessive, and to explain the results it is necessary to assume that the female is not only heterozygous for the barred character, but also for sex, with the female sex-factor dominant. The recessive character in this case is linked to the female sex chromosome, or, as Bateson described it, the dominant character is repelled by the sex-factor. We may make a diagram of the kind given by Morgan if we use a rod of different shape for the female-producing sex-chromosome, and use the black rod for the dominant character:—

BARRED female x unbarred male BX uY uX uX / / BX uX uY uX BARRED male unbarred female Heterozygous Homozygous

BARRED male x unbarred female BX BX uX uY / / BX uX BX uY BARRED male BARRED female Heterozygous Heterozygous

Another case is that of tortoise-shell, i.e. black and yellow cats. The tortoise-shell with very rare exceptions is female, the corresponding male being yellow, without any black colour. Doncaster found that a yellow male mated to a black female produced black male offspring and tortoise-shell females. When a black male is mated to a yellow female, the female kittens are tortoise-shell as before, but the males yellow. The Mendelian hypothesis which explains these results is that the male is always heterozygous, or has only one colour factor whether yellow or black, and transmits these colours only to his daughters, while the female has two colour factors, either BB, YY, or BY. Thus the crosses are:—

YELLOW male x BLACK female YO male BB female / / YB female BO male Tortoise-shell female BLACK male

BLACK male x YELLOW female BO male YY female / / BY female YO male Tortoise-shell female YELLOW male

The sex must be determined therefore by the spermatozoa, as in the case of colour-blindness, etc., in man, and the colour factor must always be in the female-producing sperm.

SEXUAL DIMORPHISM

It is obvious from the above facts that however interesting and important sex-linked heredity may be, it is not the same thing as the heredity of secondary sexual characters, and does not in the least explain sexual dimorphism. In the first place, the term sex-linked does not mean occurring always exclusively in one sex, but the direct contrary— transmitted by one sex to the opposite sex—and in the second place there is no suggestion that the development of the character is dependent in any way on the presence or function of the gonad. The problem I am proposing to consider is what light the facts throw on the origin of the secondary sexual characters in evolution. In endeavouring to answer this question there are only two alternatives: either the characters are blastogenic— that is, they arise from some change in the gametocytes occurring somewhere in the succession of cell-divisions of these cells—or they arise in the soma and are impressed on the gametocytes by the influence of the soma within which these gametocytes are contained—that is to say, they are somatogenic. That characters do originate by the first of these processes may be considered to be proved by recent researches, and such characters are called mutations. There can be little doubt that the so- called sex-linked characters, of which examples have been given above, have originated in this way, and that their relation to sex is part of the mutation. According to T. H. Morgan, it is simply due to the fact that the determinants for such characters are situated in the sex-chromosome. Morgan, however, also states that a case of true sexual dimorphism arose as a mutation in his cultures of Drosphilia. The character was eosin colour in the eye instead of the red colour of the eye in the original fly. In the female this was dark eosin colour, in the male yellowish eosin. But this case differs from the characters particularly under consideration here in two points: (1) there is no suggestion that it was adaptive, (2) or that it was influenced by hormones from the gonads.

No character whose development is dependent in greater or less degree on the stimulation of some substance derived from the gonads can have originated as a mutation, because the term mutation means a new character which develops in the soma as a result of the loss or gain of some factor or determinant in the chromosomes. To say that certain mutations consist of new factors which only the development of characters in the soma when the part of the soma concerned is stimulated by a hormone, is a mere assertion unsupported at present by any evidence. As an example of the way in which Mendelians misunderstand the problem to be considered, I may refer to Doncaster's book, The Determination of Sex [Footnote: Camb. Univ. 1914, p. 99.] in which he remarks: 'It follows that the secondary sexual characters cannot arise simply from the action of hormones; they must be due to differences in the tissues of the body, and the activity of the ovary or testis must be regarded rather as a stimulus to their development than as their source of origin.' This seems to imply a serious misunderstanding of the idea of the action of the hormones from the gonads and of hormones in general. No one would suggest that the hormones from the testis should be regarded as in any sense the origin of the antlers of a stag. If so, why should not antlers equally develop in the stallion or in the buck rabbit, or indeed in man? How far Doncaster is right in holding that the soma is different in the two sexes is a question already mentioned, but it is obvious that in each individual the somatic sexual characters proper to its species are present potentially in its constitution by heredity—in other words, as factors or determinants in the chromosomes of the zygote from which it was developed; but the normal development of such characters in the individual soma is either entirely dependent on the stimulus of the hormone of the gonad or is profoundly influenced by the presence or absence of that stimulus. The evidence, as we have seen, proves that, at any rate in the large number of cases where this relation between somatic sex-characters and hormones produced by the reproductive organs exists, the characters are inherited by both sexes. In one sex they are fully developed, in the other rudimentary or wanting. But the sex, usually the female, in which they are rudimentary or wanting is capable of transmitting them to offspring, and also is capable of developing them more or less completely when the ovaries are removed, atrophied or diseased. If we state these facts in the terms of our present conceptions of chromosomes and determinants or factors, we must say that the factors for these characters are present in the chromosomes of both male and female gametes. The question then is, how did these factors arise? If they were mutations not caused by any influence from the exterior, what is the reason why these particular characters which alone have an adaptive relation to the sexual or reproductive habits of the animal are also the only characters which are influenced by the hormones of the reproductive organs? The idea of mutations implies neither an external relation nor an internal relation in the organ or character; but these characters have both, the external relation in the function they perform in the sexual life of the individual, the internal relation in the fact that their development is affected by the sexual hormones. There is no more striking example of the inadequacy of the current conceptions of Mendelism and mutation to cover the of bionomics and evolution.

The truth is that facts and experiments within a somewhat narrow field have assumed too much importance in recent biological research. No increase in the number of facts or experimental results of a particular class will compensate for the want of sound reasoning and a comprehensive grasp of the phenomena to be explained. The coexistence of the external and the internal relation in the characters we are considering suggests that one is the cause of the other, and as it is obvious that the relation for instance of a stag's antlers to a testicular hormone could not very well be the cause of the use of the antlers in fighting, the reasonable suggestion is that the latter is the cause of the former. We have already seen that the development and shedding of the antler are processes of essentially the same kind physiologically, or pathologically, as these which can be and are occasionally produced in the individual soma by mechanical stimulus and injury to the periosteum. The fact that a hormone from the testis affects the development of the antler, as well as our knowledge of hormones in general, suggests a special theory of the heredity of somatic modifications due to external stimuli. Physiologists are apt to look for a particular gland to produce every internal secretion. But the fact that the wall of the intestine produces secretion, which carried by the blood causes the pancreas to secrete, shows that a particular gland is not necessary. There is nothing improbable in supposing that a tissue stimulated to excessive growth by external irritation would give off special substances to the blood. We know that living tissues give off products, and that these are not merely pure CO2 and H2O, but complicated compounds. The theory proposed by me in 1908 was that we have within the gonads numerous gametocytes whose chromosomes contain factors corresponding to the different parts of the soma, and that factors or determinants might be stimulated by products circulating in the blood and derived from the parts of the soma corresponding to them. There is no reason to suppose that an exostosis formed on the frontal bone as a result of repeated mechanical stimulation due to the butting of stags would give off a special hormone which was never formed in the body before, but it would probably in its increased growth give off an increased quantity of intermediate waste products of the same kind as the tissues from which it arose gave off before. These products would act as a hormone on the gametocytes, stimulating the factors which in the next generation would control the development of the frontal bone and adjacent tissues.

The difficulty of this theory is one which has occurred to biologists who have previously made suggestions of a connexion between hormones and heredity—namely, how hormones or waste products from one part of the body could differ from these from the same tissue in another part of the body. If there were no special relation, hypertrophy of bone on one part of the body such as the head, would merely stimulate the factor for the whole skeleton in the gametocytes, and the result would merely be an increased development of the whole skeleton. On the other hand, we have the evident fact that a number of chromosomes formed apparently of the same substance, by a series of equal chromosome divisions determine all the various special parts of the complicated body. This is not more difficult to understand than that every part of the body should give off special substances which would have a special effect on the corresponding parts of the chromosomes. We know that skin glands in different parts of the body produce special odours, although all formed of the same tissue and all derived from the epidermis. It seems not impossible that bones of different parts of the body give off different hormones. If the factors in the gametes were thus stimulated they would, when they developed in a new individual, product a slightly increased development of the part which was hypertrophied in the parent soma. No matter how slight the degree of hereditary effect, if the stimulation was repeated in every generation, as in the case of such characters as we are considering it undoubtedly was, the hereditary effect would constantly increase until it was far greater than the direct effect of the stimulation. We may express the process mathematically in this way. Suppose the amount of hypertrophy in such a case as the antlers to be x, and that some fraction of this is inherited. Then in the second generation the same amount of stimulation together with the inherited effect would produce a result equal to x+x/n. The latter fraction being already hereditary, a new fraction x/n would be added to the heredity in each generation, so that after m generations the amount of hereditary development would be x+mx/n. If n were 1000, then after 1000 generations the inherited effect would be equal to x. This, it is true, would not be a very rapid increase. But it is possible that the fraction x/n would increase, for the heredity might very well consist not only in a growth independent of stimulation, but in an increasing response to stimulation, so that x itself might be increasing, and the fraction x/n would become larger in each generation. The death and loss of the skin over the antler, originally duo to the laceration of the skin in fighting, has also become hereditary, and it is certainly difficult to conceive the action of hormones in this part of the process. All we can suggest is that the hormone from the rapidly growing antler, including the covering skin, is acting on the corresponding factor in the gametocytes for a certain part of every year, and then, when the skin is stripped off, the hormone disappears. The factor then may be said to be stimulated for a time and then the stimulus suddenly ceases. The bone also begins to die when the skin and periosteum is stripped off, and the hormone from this also ceases to be produced.

The annual shedding and recrescence of the antler, however, is only to be understood in connexion with the effect of the testicular hormone. According to my theory there are two hormone actions, the centripetal from the hypertrophied tissue to the corresponding factor in the gametocytes, and the centrifugal from the testis to the tissue of the antler or other organ concerned. The reason why the somatic sexual character does not develop until the time of puberty, and develops again each breeding season in such cases as antlers, is that the original hypertrophy due to external stimulation occurred only when the testicular hormone was circulating in the blood. The factor in the gametocytes then in each generation acted upon by both hormones, and we must suppose that in some way the result was produced that the hereditary development of the antler in the soma only took place when the testicular hormone was present. It is to be remembered that we are unable at present to form a clear conception of the process of development, to understand how the simple fertilised ovum is able by cell-division and differentiation to develop into a complicated organism with organs and characters predetermined in the single cell which constitutes the ovum. If we accept the idea that characters are represented by particular parts of the chromosomes, according to Morgan's scheme, our theory of development is the modern form of the theory of preformation. When in the course of development the cells of the head from which the antlers arise are formed, each of these cells must be supposed to contain the same chromosomes as the original ovum from which the cells have descended by repeated cell-division. The factors in these chromosomes corresponding to the forehead have been stimulated while in the parent animal by hormones from the outgrowth of tissue produced by external mechanical stimulation, while at the same time they were permeated by the testicular hormone produced either by the gametocytes themselves or by interstitial cells of the testis. When the head begins to form in the process of individual development, the factors, according to my theory, have a tendency to form the special growth of tissue of which the incipient antler consists, but part of the stimulus is wanting, and is not completed until the testicular hormone is produced and diffused into the circulation—that is to say, when the testes are becoming mature and functional.

I do not claim that this theory in complete—it is impossible to understand the process completely in the present state of knowledge—but I maintain that it is the only theory which affords any explanation of the remarkable facts concerning the influence of the hormones from the reproductive organs on the development of secondary sexual characters, while at the same time explaining the adaptive relation of these characters or organs to the sexual habits of the various species. On the mutation hypothesis, adaptation is purely accidental. T. H. Morgan considers that the appearance of two slightly different shades of eye colour in male and female in a culture of a fruit-fly in a bottle is sufficient to settle the whole problem of sexual dimorphism, and to supersede Darwin's complicated theory of sexual selection. The possibility of a Lamarckian explanation he does not even mention. He would doubtless assume that the antlers of stags arose as a mutation, without explaining how they came to be affected by the testicular hormone, and that when they arose the stags found them convenient as fighting weapons. But the complicated adaptive relations are not to be disposed of by the simple word mutation. The males have sexual instincts, themselves dependent on the testicular hormone, which develop sexual jealousy and rivalry, and the Ruminants fight by butting with their heads because they have no incisor teeth in the upper jaw, or tusks, which are used in fighting in other species. Doubtless, mutations have occurred in antlers as in other characters; in fact all hereditary characters are subject to mutation. This in the most probable explanation, not only of the occasional occurrence of hornless individual stags, but of the differences between the antlers of different species, for there is no reason to believe that the special character of the antler in each species is adapted to a special mode of fighting in each species.

The different structure of the horns of the Bovine and Ovine Ruminants is, in my view, the result of a different mode of fighting. If we suppose that the fighting was slower and less fierce in the Bovidae, so that the skin over the exostosis was subject to friction but not lacerated, the result would be a thickening of the horny layer of the epidermis as we find it, and the fact that the skin and periosteum are not destroyed explains why the horns are not shed but permanent.

There is a tendency among Mendelians and mutationists to overestimate the importance of experiments in comparison with reasoning, either inductive or deductive. Bateson, however, has admitted that Mendelian experiments and observations on mutation have not solved the problem of adaptation. It seems to be demanded, nevertheless, that characters must be produced experimentally and then inherited before the hereditary influence of external stimuli can be accepted. Kammerer's experiments in this direction have been sceptically criticised, and it must be granted that the evidence he has published is not sufficient to produce complete conviction. But experiments of this kind are from the nature of the case difficult if not impossible. There is, however, another method—namely, to take a character which is certainly to some extent hereditary, and then to ascertain by experiment if it is 'acquired.' If it be proved that a hereditary character was originally somatogenic, it follows that somatogenic characters in time become hereditary. This is the reasoning I have used in reference to my experiments on the production of pigment on the lower sides of Flat-fishes, and I obtained similar evidence with regard to the excessive growth of the tail feathers in the Japanese Tosa-fowls, [Footnote: 'Observations and Experiments on Japanese Long-tailed Fowls,' Proc. Zool. Soc., 1903.] which is a modification of a secondary sexual character. In these fowls the feathers of the tail in the hens are only slightly lengthened.

I learned from Mr. John Sparks, who himself brought specimens of the breed from Japan, that the Japanese not only keep the birds separately on high perches in special cages, but pull the tail feathers gently every morning in order to cause them to grow longer. One question which I had to investigate on my specimens, hatched from eggs obtained from Mr. Sparks, was the relation of the growth of the feathers to the moult which occurs in ordinary birds. My experiment consisted in keeping two cocks, A and B, the first of which was left to itself, while in the second the feathers were gently pulled by stroking between the finger and thumb from the base outwards. The feathers in the tail were seven pairs of rectrices, two rows of tail coverts, anterior and posterior, four or five pairs in each row, a number of transition feathers: all these were steel-blue, almost black; in front of them on the saddle were a number of reddish yellow, very slender saddle hackles.

In September 1901, when the birds ware just over three months old, the adult feathers of the tail were all growing. The growing condition can be distinguished by the presence of a horny tubular sheath extending up the base of the feather for about one inch. When growth ceases this sheath is shed. In cock A growth continued till the end of the following March, when the longest feathers, the central rectrices, 2 feet 4-1/2 inches long. One of the feathers—namely, one of the anterior tail coverts—was accidentally pulled out on 11th February 1902, when it was 15-1/4 inches long and had nearly ceased to grow and formed its quill, and it immediately began to grow again and continued to grow till the following September, when it was accidentally broken off at the base: it was then 18 inches (44.5 cm.) long.

The effect of stroking in cock B was to pull out from time to time one of the growing feathers. Of the original feathers, one, the left central posterior covert, continued to grow till 13th July 1902, when it was 2 feet 9-1/2 inches long without the part contained in the follicle. All the feathers pulled out immediately commenced to grow again, except the last two pulled out 27th May and 13th July, which did not grow again till the following moulting season, in September.

The first right central rectrix in cock B was accidentally pulled out on 13th April 1902, when it was 2 feet 9-7/8 inches long. Its successor began to grow immediately, and in course of time pieces of it were broken off accidentally without injury to the base in the socket, which continued to grow until 16th June 1905, when it torn out of its socket. The total length of the feather with the pieces previously broken off, which were measured and preserved, was 11 feet 5-1/2 inches. It therefore continued to grow without interruption for three years and two months at an average rate of 3.6 inches per month.

In cock A only four of the short outer rectrices were moulted in the beginning of September 1902: the longer feathers—namely, central rectrices and tail coverts—which ceased to grow naturally in the spring of 1902, were not moulted till the beginning of October. This shows the great importance of pulling out the feathers as soon as they show signs of ceasing to grow, in order to obtain the abnormally long feathers. The central rectrices continued to grow till the beginning of September 1903, when that of the left side was 3 feet 6 inches long, that of the right about an inch shorter. The coverts had ceased to grow of their own accord some time before this, and the central ones of the posterior row were about 3 feet long.

As it seemed possible that there was some natural congenital difference in growth of feathers between cocks A and B, I commenced early in March 1903 to pull and stroke the feathers of the left side only in cock A, leaving those of the right side untouched. On 30th July on the left side the central rectrix and the first and second posterior coverts were still growing, on the right side the central rectrix was also growing, but the first and second posterior coverts had ceased growth and formed their quills. The first posterior covert on the left or pulled side was 3 inches longer than that of the right. The second posterior covert on the left side was still longer. The first and second posterior coverts of left side did not cease growth till 26th August. On 2nd September the left central rectrix was almost at the end of its growth, the right had ceased to grow a little before. The left was about an inch longer than the right. Thus both in length in duration of growth the feathers of the pulled side were longer than those of the right, and this was the result of treatment continued only six months, and commenced some months after the feathers had begun to grow. I have no doubt, however, that the pulling out of the feather as soon as it shows signs of forming quill, so that its successor at once grows again, is even more important in producing the great length of feather than the stroking of the feather itself.

In this case, then there is no doubt (a) that the long-tailed birds are artificially treated with the utmost care and ingenuity by the Japanese, who produced them; (b) that the mechanical stimulus in my experiments did cause the feathers to grow for a longer period and attain greater length; (c) that the tendency to longer growth is, even when no treatment is applied, distinctly inherited. It is a legitimate and logical conclusion that the inherited tendency is the result of the artificial treatment. No other breed of fowls shows such excessive growth of tail feathers. It may be admitted that individuals differ considerably in their congenital tendency to greater growth, i.e. greater length of the tail feathers, but according to my views this is not contradictory to the main conclusion, for every hereditary character shows individual variation.

It may be pointed out here that on the Lamarckian theory the conception of adaptations is not teleological: they do not exist for a certain purpose, but are the result of external stimulations arising from the actions and habits of the organism. The latter conception is the more general, for cases of somatic sexual characters exist which cannot be said to have a use or function. For example, the comb and wattles of Gallus are sexually dimorphic, being in the original species larger in the cock than in the hen. There is no convincing evidence that these appendages are either for use or ornament. They are, in fact, a disadvantage to the bird, being used by his adversary to take hold of when he strikes. The first thing that happens when cocks fight is the bleeding and laceration of the comb, as they peck at each other's heads. This laceration of the skin is, in my view, the primary cause of the evolution of these structures, leading to hypertrophy. But in this, as in other cases, the hereditary result is regular, constant, and symmetrical, while the immediate effect on the individual is doubtless irregular.



CHAPTER V

Mammalian Sexual Characters Evidence Opposed To The Hormone Theory

Perhaps the most remarkable of all somatic sexual characters are those which are almost universal in the whole class of Mammalia, the mammary glands in the female, the scrotum in the male. We have considered the evidence concerning the relation of the development and functional action of the milk glands to hormones arising in the ovary or uterus, now we have to consider the origin of the glands and of their peculiar physiology in evolution. The obvious explanation from the Lamarckian point of view, and in my opinion the true one, is that they owed their origin at the beginning to the same stimulation which is applied to them now in every female mammal that bears young. There is, as we have seen, a difficulty in explaining how the occurrence of parturition causes the secretion of milk to begin, but it is certain that the secretion soon stops if the milk is not drawn from the glands by the sucking action of the offspring, or the artificial imitation of that action. A cow that is not milked or milked incompletely ceases to give milk. When the stimulus ceases, lactation ceases. The pressure of the secretion in the alveoli causes the cells to cease to secrete, much in the same way that pressure in the ureters injures the secretory action of the renal epithelium. In the earliest Mammals we may suppose that the young were born in a well-developed condition, for at first the supply of milk would not have been enough to sustain them for a long time as their only food. We must also suppose that the mother began to cherish the young, keeping them in contact with her abdomen. Then being hungry they began to suck at her hair or fur. The actual development of the milk glands in Marsupials has been described by Bresslau [Footnote: Stuttgart, 1901.] and by O'Donoghue. [Footnote: Q.J.M.S., lvii., 1911-12.] The rudiment of the teat is a depression or invagination of the epidermis from the bottom of which six stout hairs arise. The follicles of these hairs extend down into the derma, and from the upper end of the follicle, i.e. near the aperture of the invagination, a long cellular outgrowth extends down into the derma, branches at its end, and becomes hollow. These branches are the tubules of the future milk gland. Another outgrowth from the follicle forms a sebaceous gland. Later on the hairs and the sebaceous glands entirely disappear, and the milk gland alone is left with its tubules and ducts opening into the cavity of the teat. This is clear evidence that the milk gland was evolved in connexion with hairs, and was an enlargement of glands opening into the hair follicle, but it is difficult to understand why a sebaceous gland is developed and afterwards disappears. This would seem to indicate that the milk gland was not a hypertrophied sebaceous gland, but a distinct outgrowth, which however had nothing to do with sweat glands.

That the intra-uterine gestation, or its cessation, were not originally necessary to determine the functional periodicity of the milk glands is proved by their presence in the Monotremes, which are oviparous. It is evident from the conditions in these mammals that both hair and milk glands were evolved before the placenta.

It may also be pointed out here that, according to the evidence of Steinach, in the milk glands at least among somatic sexual characters there is no difference between the male and female in the heredity of the organs. The zygote therefore, whether the sex of it is determined as male or female, has the same factor for the development of milk glands. On the chromosome theory as formulated by Morgan this factor must be in the somatic chromosomes and not in the sex-chromosomes, and must be present in every zygote. All the cells of the body, assuming that somatic segregation does not occur, must possess the same chromosomes as the zygote from which it developed, and whether the sex chromosomes are XX or XY or X, there must be at any rate one chromosome bearing the factor for milk glands. The functional development of these depends normally, according to the evidence hitherto discovered, on the presence or absence of hormones from the ovary or from the uterus.

If we attribute, as in my opinion we must, the primary origin of the milk glands in evolution to the mechanical stimulus of sucking, we may attempt to reconstruct the stages of the evolution of the present relation of the glands to the other organs and processes of reproduction. In the earliest stage represented by the Monotremata or Prototheria, there was no intra-uterine development. We must suppose that in the beginning the sucking stimulus caused both growth and secretion, for at first there was nothing but sebaceous or sweat glands, and although a mutation might be supposed to have produced larger glands, no mutation could explain the influence of hormones on the growth and function of such glands. Then heredity of the effect of stimulus took place to some slight degree, and this would occur, according to my theory, only in the presence of the hormone from the ovary in the same condition as that in which the modification was first caused. This would be of course after ovulation, and after hatching of the eggs. In the next stage, if we adopt the modern view that Marsupials are descended from Placental Mammals, the eggs would be retained for increasing periods in the uteri, and would be born in a well-developed condition, since lactation would demand active sucking effort on the part of the young. The early Placentalia would inherit from the Monotreme-like ancestors the development of the milk glands after ovulation, although no sucking was taking place while the young were inside the uterus. It seems probable that the relation between parturition and actual milk secretion originated with the sucking stimulus of the young after birth.

There is good evidence that the secretion of milk may continue almost indefinitely under the stimulus of sucking or milking. Neither menstruation nor gestation put an end to it. Cows may continue to give milk until the next parturition, and if castrated during lactation will continue to yield milk for years. Women also may continue to produce milk as long as the child is allowed to suck, and this has been in some cases two or three years or even more. Moreover, lactation may be induced by the repeated act of sucking without any gestation. This has happened in mares, virgin bitches, mules, virgin women, and in one woman lactation continued uninterruptedly for forty-seven years, to her eighty-first year, long after the ovary had ceased to be functional. Lactation has also been induced in male animals, e.g. in a bull, a male goat, male sheep, and in men. [Footnote: Knott, 'Abnormal Lactation,' American Medicine, vol. ii (new series), 1907.] We may conclude, therefore, that the secretion of milk normally begins by heredity after parturition, and this, in accordance with what we have learned about hormones in connexion with the reproductive system, is probably the consequence of the withdrawal of the hormone absorbed from the foetus. I do not think it is necessary to suppose, as do Lane-Claypon and Starling, that the hormone physiologically inhibits the dissimilative process and augments the assimilative, and that the withdrawal of the hormone at parturition therefore causes the dissimilative process, i.e. secretion of milk. My conclusion is that the process of secretion set up by the mechanical stimulus of sucking is inherited as it was acquired, so that it only begins to take place in the individual in the absence of the hormone from the foetus, which was absent when the process was acquired. The growth of the gland during gestation would then be due to the postponement of the process of secretion in consequence of the presence of the foetal hormone, and in this way this hormone has become in the course of evolution at once the stimulus to growth and the cause of the inhibition of secretion.

This interpretation does not, however, agree with the case of Dasyurus. If the foetal hormone is absorbed from the pouch, as I have suggested, in order to explain the persistence of the corpora lutea during lactation, then the secretion of milk after parturition ought not to take place. But in this case the sucking stimulus has been applied to the glands after a very short gestation, while the hormone from the foetus is being absorbed in the pouch, and therefore the hereditary correlation between secretion and absence of foetal hormone may be assumed to have been lost in the course of evolution.

We have next to consider the question of the evolution of the corpora lutea. If these bodies are formed only in Mammals which have uterine gestation, and not in Prototheria, they cannot be the only essential source of the hormone which stimulates the development of the milk glands, since the latter develop in Prototheria. Again it is difficult, it might be said impossible, to believe that an accidental mutation gave rise to corpora lutea the secretion of which caused uterine gestation and ultimately the formation of the placenta. It seems more probable that the retention of the originally yolked ova within the oviduct, however this retention arose, was the essential cause of the formation of the placenta and all the changes which the uterus undergoes in gestation. The absorption of nutriment from the walls of the uterus, and the chemical and mechanical stimulation of those walls, might well be the cause of the diversion of nutrition from the ovary, leading gradually to the decline of the process of secretion of yolk in the ova.

The conceptions and the mode of reasoning of the physiologist are very different from those of the evolutionist. The former concludes from certain experiments that a given organ of internal secretion has a certain function. The corpora lutea, for example, according to one theory are ductless glands, the function of whose secretion is to establish ova in the uterus and promote their development. Another function suggested for the secretion of the corpora lutea is to prevent further ovulation during pregnancy. The evolutionist, on the other hand, asks what was the origin of this corpora lutea, why should the ruptured ovarian follicles after the escape of the ova in Mammals undergo a progressive development and persist during the greater part of the whole of pregnancy? It seems obvious that the corpora lutea in evolution were a consequence of intra-uterine gestation, for they occur only in association with this condition, and it is impossible to suppose that a mutation could arise accidentally by which the ruptured follicles should produce a secretion which would cause the fertilised ova to develop within the oviducts. The developing ovum within the uterus may, however, reasonably be supposed to give off something which is absorbed into the maternal blood, and this something would be of the same nature as that which was given off by the ovum while still within the ovarian follicle. The presence of this hormone might cause the follicular cells to behave as though the ovum was still present in the follicle, so that they would persist and not die and be absorbed. But this leaves the question, what is lutein and why is it secreted? Lutein is a colouring matter sometimes found in blood-clots, and probably derived from haemoglobin. In the corpus luteum the lutein is contained in the cells, not in a blood-clot.

Chemical investigation shows that the lutein of the corpus luteum is almost if not quite identical with the colouring matter of the yolk in birds and reptiles. Escher [Footnote: Ztschr. f. Physiol. Chem., 83 (1912).] found that the lutein of the corpus luteum had the formula C{40}H{56} and was apparently identical with the carotin of the carrot, while the lutein of egg-yolk was C{40}H{56}O{2} and more soluble in alcohol, less soluble in petroleum ether, than that of the corpus luteum. The difference, if it exists, is very slight, and it is evident that one compound could easily be converted into the other. Moreover, the hypertrophied follicular cells which constitute the corpus luteum secrete fat which is seen in them in globules. The similarity of their contents therefore to yolk is very remarkable, and it may be suggested that the hormones absorbed from the ovum or embryo in the uterus acts upon the follicular cells in such a way as to cause them to secrete substances which in the ancestor were passed on to the ovum and formed the yolk. It may be urged that this idea is contradictory to the previous suggestion that the absorption of nourishment by the intra-uterine embryo was the cause of the gradual decline of the process of yolk-secretion by the ova in the ovary, but it is not really so. Originally in the reptilian ancestor, or in the Monotreme, the ovum in the follicle secreted yellow-coloured yolk. The materials for this, at any rate, passed through the follicle cells, and it is probable that these cells were not entirely passive, but actively secretory in the process. Substances diffusing from the ovum would be present in the follicle cells during this process, and probably act as a stimulus. The same substances diffusing from the ovum during its development in the uterus would continue to stimulate the follicle cells, and thus explain not merely their persistence, but their secretory activity. The ovum being no longer present in the ovary, the secretions would remain in the follicular cells, and the corpus luteum would be explained.

If this theory is sound, it would follow that corpora lutea are not formed in cases where the ova are not retained in the oviduct during their development. The essential process in the development of these structures is the hypertrophy and, in some cases at least, multiplication of the follicular cells in the ruptured follicle. I have already mentioned that this process does not occur in Teleosteans whose ovaries were studied by me. These were species of Teleosteans in which fertilisation is external. Marshall, in his Physiology of Reproduction, [Footnote: London, 1910, p. 151.] quotes a number of authors who have published observations on the changes occurring in the ruptured follicle in the lower Vertebrata, and also in the Monotremes. According to Sandes, [Footnote: 'The Corpus Luteum of Dasyurus,' Proc. Lin. Soc., New South Wales, 1903.] in the latter there is a pronounced hypertrophy of the follicular epithelium after ovulation, but no ingrowth of connective tissue or blood-vessels from the follicular wall. Marshall himself examined sections of the corpus luteum of Ornithorhynchus and saw much hypertrophied and apparently fully developed luteal cells, but no trace of any ingrowth from the wall of the follicle. This fact would appear to be quite inconsistent with the theory above proposed, but it must be remembered that the ovum of Monotremes is known to remain for a short period in the oviduct, or in other words to pass through it very slowly, and to absorb fluid from its walls, as shown by the considerable increase in size which the ovarian ovum undergoes before it is laid. It would be interesting to know how long the rudimentary corpus luteum persists in Ornithorhynchus: the period, according to my views, should be very short. It is remarkable that in the results quoted by Marshall a well-developed corpus luteum was found and exclusively found in the lower Vertebrates which are viviparous. For example, among fishes in the Elasmobranchs Myliobatis and Spinax; in Teleosteans, in Zoarces; in Reptiles, in Anguis and Seps. Buehler on the other hand, confirmed my own negative result with regard to oviparous Teleosteans, and also found no hypertrophy of the follicle in Cyclostomes which are also oviparous. In the viviparous forms mentioned there is yolk in the ovum which is retained in oviduct or ovary, but additional nutriment is also absorbed from the uterine or ovarian walls. In these cases there is no placenta and generally no adhesion of ovum or embryo to walls of oviduct or ovary. These facts alone would be sufficient to disprove the theory that the corpora lutea are organs producing a secretion whose function is to cause the attachment of the embryo to the uterine mucosa. It is also, in my opinion, unreasonable to suppose that the rudimentary corpora lutea of lower viviparous Vertebrates arose as a mutation the result of which was to cause internal development of the ovum. Habits might easily bring about retention of the fertilised ova for gradually increasing periods, [Footnote: According to Geddes and Thomson (Evolution of Sex, 1889), the common grass-snake has been induced under artificial conditions to bring forth its young alive.] and the correlation between the retained developing ova and the hypertrophy of the ruptured follicles is comprehensible on my theory of the influence of substances absorbed by the walls of oviduct or ovary from the developing ovum.

The case of Dasyurus, however, seems inconsistent with this argument, for, as previously mentioned, Sandes found that in this Marsupial the corpora lutea persisted during the greater part of the period of lactation, which continues for four months after parturition. During the whole of this time there are no embryos in the uteri, and therefore it might be urged absorption of hormones from the embryos cannot be the cause of the persistence of corpora lutea in pregnancy. But it seems to me that a complete answer to this objection is supplied by the peculiar relations of the embryos to the pouch in Dasyurus and other Marsupials. The skin of the pouch while the embryos are in it is very soft, congested, and glandular; at the same time the embryos when transferred to the pouch at parturition are very small, immature, and have a soft delicate skin. The relation of embryos to pouch in Dasyurus, therefore, is closely similar to that of embryos to uterus after the first few days of pregnancy in the Eutheria. It is true there is no placenta, but the mouths of the embryos are in very close contact with the teats, and both the skin of the embryos and that of the pouch are soft and moist. If any special substances are given off by the embryos in the uterus in ordinary gestation, the same substances would continue to be given off by the embryos in the marsupial pouch, and these must be absorbed by the skin of the pouch. In this way it seems to me we have a logical explanation of the fact that the corpora lutea in the Marsupial are not absorbed at parturition as in Eutheria. As Sandes says the 'greater part of the period of lactation,' it would appear that absorption of the corpora lutea takes place when the young Dasyurus have grown to some size, become covered with hair, and are able to leave the teats or even the pouch at will. Under these conditions it is obvious that diffusion of chemical substances from the young through the walls of the pouch would come to an end. It would be interesting in this connexion to know more of the relation of egg and embryo to the pouch and to the corpora lutea in Echidna. In Ornithorhynchus the eggs are hatched in a nest and there is no pouch.

On this view that the corpora lutea are the result, not the cause, of intra-uterine gestation, it would no longer be possible to maintain the theory that the corpus luteum in the human species is the cause by its internal secretion of the phenomenon of menstruation. This was the theory of Born and Fraenkel. [Footnote: See Biedl, Internal Secretory Organs (Eng. trans.), 1912, p. 404.] Biedl's conclusion is that the periodic development and disintegration of the uterine mucous membrane in the menstrual cycle is due to the hormone of the interstitial cells of the ovary. Leopold and Ravana found that ovulation as a rule coincides with menstruation, but may take place at any time. Here, again, the problem must be considered from the point of view of evolution. It can scarcely be doubted that the thickening and growth of the mucous membrane in the menstrual cycle is of the same nature as that which takes place in pregnancy. When the ovum or ova are not fertilised the development comes to an end after a certain time, differing in different species of Mammals, and the membrane sloughs, returns to its original, state, and then begins the same process of development again.

Menstruation, then, must be interpreted as an abortive parturition, both in woman and lower Mammals, though in the latter it is not usually accompanied by hemorrhage, and is called pro-oestrus. The question then to be considered is, what determines parturition and menstruation? The presence of the fertilised ovum must have been the original cause of the hypertrophy of the uterine mucous membrane, and in its congenital or hereditary development the chemical substances diffusing from the ova in the uterus or even in the Fallopian tube may well be the stimulus starting the hypertrophy. But what determines the end of the pregnancy? Is it merely the increasing distension of the uterus by the developing foetus? This could scarcely be the case in the Marsupials in which the foetus when born is quite minute. Nor can we attribute parturition to renewed ovulation, for this occurs in Dasyurus only once a year. All we can suggest at present is that a certain periodic development takes place by heredity in presence of the hormones exuded by the fertilised ovum and the embryo developed from it. When the ovum or ova, not being fertilised, die the period of development is (usually) shortened and pro-oestrus or menstruation occurs. In the dog, however, the period of the oestrus cycle is about the as that of gestation—namely, six months.

The so-called descent of the testicles occurs exclusively in Mammals, in which with a few important exceptions it is universal. This is a very remarkable case of the change of position of an organ in the course of development. The original position of the testis on either side is quite similar to that of the same organ in birds or reptiles. The genital ridge runs along the inner edge of the mesonephros, with which the testicular tubules become connected. The testis, with the mesonephros, forming the epididymis, closely attached to it, projects into the coelom, and without losing its connexion with the peritoneum changes its position gradually during development, passing backwards and downwards until it comes to lie over the wall of the abdomen just in front of the pubic symphysis of the pelvic girdle. There the abdominal wall on either side of the middle line becomes thin and distended to form a pouch, the scrotal sac, into which the testis passes, still remaining attached to the peritoneum which lines the pouch, while the distal end of the vas deferens retains its original connexion with the urethra. The movement of the testis can thus be accurately described as a transposition or dislocation.

Various causes have been suggested for the formation of the scrotum, but no one has ever been able to suggest a use for it. It has always been quite impossible to bring it within the scope of the theory of natural selection. The evolution of it can only be explained either on the theory of mutation or some Lamarckian hypothesis. The process of dislocation of the testis does not conform to the conception of mutation, nor agree with other cases of that phenomenon. A mutation is a change of structure affecting more or less the whole soma, but showing itself especially in some particular organ or structure. But I know of no mutation occurring under observation which consisted, not in a change of structure or function, but merely in a change of position of an organ from one part of the body to another, and moreover a change which takes place by a continuous process in the course of development. If the testes were developed from the beginning in a different part of the abdomen, there might be some reason in calling the change a mutation. Moreover, if it is a mutation, why has it never occurred in any other class of Vertebrates except Mammals?

In 1903 Dr. W. Woodland published [Footnote: Proc. Zool. Soc., 1903, Part 1.] a Lamarckian theory of this mammalian feature, the probability of which it seems to me has been increased rather than decreased by the progress of research concerning heredity and evolution since that date. Dr. Woodland correlated the dislocation of the testes with the special mechanical features of the mode of locomotion in Mammalia. His words are: 'The theory here advocated is to the effect that the descent of the testes in the Mammalia has been produced by the action of mechanical strains causing rupture of the mesorchial attachments, such strains being due to the inertia of the organs reacting to the impulsiveness involved in the activity of the animals composing the group.' The 'impulsiveness' is the galloping or leaping movement which is characteristic of most Mammals when moving at their utmost speed, as seen, for example, in horses, deer, antelopes, dogs, wolves, and other Ungulata and Carnivora. It is obvious that when the body is descending to the ground after being hurled upwards and forwards, the abdominal organs have acquired a rapid movement downwards and forwards; when the body reaches the ground its movement is stopped suddenly, while the abdominal organs continue to move. The testes therefore are violently jerked downwards away from their attachments and at the same time forward. The check to the forward movement, however, is momentary, while the body is immediately thrown again upwards and forwards, which by the law of inertia means that the testes are thrown still more downwards and backwards. There is no reason to suppose, as Dr. Woodland suggests, that any rupture of the mesorchium was the usual result of these strains, but a constant pull or tension was caused in the direction in which the testes actually move during development. On this theory we have to consider (1) how such strains could cause a shifting of the peritoneal attachment, (2) why the testes should be supposed to be particularly affected more than other abdominal organs. The answer to the first question is that the strains would cause a growth of the connecting membrane (mesorchium) at the posterior end, accompanied by an absorption of it at the anterior end. The answer to the second question is that the testes are at once the most compact and heaviest organs in the abdomen, and at the same time the most loosely attached. The latter statement does not apply to the mesonephros or epididymis which has moved with the testis, but the latter cannot function without the former, and it may be supposed that the close attachment of the epididymis to the testis had come about in the early Mammalia before the change of position was evolved.