FOREWORD 



development of the gonads and the meta- 

 morphosis of the Wolffian and Miillerian 

 ducts into the secondary internal reproduc- 

 tive organs was rapidly worked out in 

 animals of every vertebrate order, by an 

 army of in\'estigators too numerous to 

 mention in a short resume. The story of the 

 first appearance of primordial germ cells 

 and their migration through the tissues of 

 the embryo to the newly forming gonads, 

 adumbrated in the 1880's by the work of 

 Semon, was confirmed and extended to 

 several species of mammals. If in these 

 latter creatures and in the human species, 

 th(> complete line of descent from the 

 fertilized ovum to the first appearance of 

 the germ cells is till not as clear as in many 

 lower forms, enough at least was discovered 

 within a few decades to indicate an essential 

 similarity in the history of the germ cells 

 in all vertebrates. 



To the embryologists of Europe and 

 America w^e owe in large part also the 

 successful analysis of the mammalian repro- 

 ductive cycle that has been achieved during 

 this half century. In order to procure 

 mammalian embryos of known age the time 

 of ovulation and fertilization had to be 

 related to the outward manifestations of the 

 estrous cycle. Comparati^'e description of 

 the cycles of the various mammals for this 

 purpose was climaxed by the discovery, or 

 rather rediscovery and practical application 

 of cyclic changes in the vaginal epithelium 

 by C. R. Stockard and G. X. Papanicolaou. 

 The vaginal smear method, thus introduced 

 to the experimental laboratories, made pos- 

 sible a wide range of investigations on the 

 physiology and biochemistry of the cycle 

 and the ovarian hormones. As apphed to the 

 white rat by Herbert M. Evans and J. A. 

 Long it became a basic tool in such studies. 



Another influence which also greatly for- 

 warded investigation of the ovarian cycle 

 has already been mentioned. This was the 

 efTort of the gynecologists and especially 

 gynecologic pathologists to interpret cychc 

 events in the human ovary and uterus. One 

 of the most notable American discoveries, 

 that of the influence of the corpus luteum 

 in decidua formation by Leo Loeb, stemmed 

 from his familiarity with the German studies 

 on the human cvcle. Much of our knowledge 



of th(^ corpus luteum and its hormone, 

 progesterone, was in fact won by investiga- 

 tors who approached the problem through 

 gynecology. 



Had it not b(>en for the first World War, 

 moreover, European gynecologic experi- 

 menters might have attained clear knowl- 

 edge of the estrogenic hormones, for even 

 before 1900 Emil Knauer and Josef Halban 

 of Vienna had demonstrated in a preliminary 

 w^ay the endocrine dominance of the ovaries 

 over the uterus, and by 1913 various in- 

 vestigators, notably Henri Iscovesco of Paris 

 and Otfried Fellner of Vienna, had pre- 

 pared crude extracts which we now know 

 contained estrogens. It remained, however, 

 for the American zoologist-anatomist Edgar 

 Allen and his biochemical colleague E. A. 

 Doisy, e(iuipped with the vaginal smear 

 method of testing ovarian hormone action, 

 to isolate an estrogen from the fluid of the 

 Graafian follicles, thus starting an era of 

 ovarian endocrinology which has ultimately 

 resulted in clear definition and discrimina- 

 tion of estrogens and progestins and their 

 respective effects upon the uterus and other 

 organs of the reproductive system. Applying 

 this new knowledge to the complexities of the 

 human reproductive cycle, the zoologists, 

 embryologists, gynecologists and endocri- 

 nologists, among them several distinguished 

 contributors to the first edition of this 

 work, have combined forces to work out a 

 clear account of the endocrine basis of 

 menstruation and the implantation of the 

 primate embryo. 



The parallel story of the hormones of the 

 testis can be read in the successive editions 

 of Sex and Internal Secretions. Berthold's 

 proof, published in 1849, that in fowls the 

 testis presides over the development of the 

 cock's comb, wattles, and spurs ultimately 

 led to the isolation of the first known 

 androgen in F. C. Koch's laboratory at 

 Chicago, and thence to the development of 

 a great body of knowledge about androgenic 

 steroids. 



The more complex history of the hor- 

 mones of the hypophysis, becoming some- 

 what clearer in each successive edition of 

 this work, well illustrates a main theme of 

 this introductory essay, namely the de- 

 pendence of scientific advance upon the 



