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. Bühler 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.