EDCAR ALLEN 



to the genital tract comes from the corpus 

 hiteum and then, after noting that "the 

 follicles are the only remaining ovarian 

 possibility," continued, "the presence of 

 maturing ova in large follicles is the cause 

 of the prooestrum and oestrus" and "the 

 renewal of the ova at ovulation (or their 

 atresia if this fails to occur) is the primary 

 cause of the degenerative changes of the 

 metoestrum." 



Except for the addition of the active role 

 of the estrogenic substances contained in 

 the follicular fluid, demonstrated by him- 

 self and Edward A. Doisy less than two 

 years later, the pattern of Allen's thought 

 for the next 20 years was contained in his 

 thesis — the cyclic origin of ova from the 

 germinal epithelium, the primacy of the 

 ovum, the growth effects of estrogens, the 

 consequences of their withdrawal, a dis- 

 counting (the word used in his thesis) of 

 the importance of the hormone of the 

 corpus luteum in the regulation of reproduc- 

 tive phenomena. 



Rarely has so much of the important 

 conceptualization of a pre-eminent scientist 

 been "roughed in" in his thesis. Also of 

 interest is the place of the thesis in the 

 history of American anatomy. It was written 

 at a time when the emphasis was shifting 

 from structural anatomy to functional anat- 

 omy. Rightly or wrongly, there were then, 

 as there are now, those who feel that this 

 trend could go too far. Allen seems to have 

 been caught in this controversy. At all 

 events, he must have felt compelled to 

 enlist the help of friends at Brown, for it 

 was the men there with their orientation 

 toward biology who seem to ha^'e been 

 less concerned with the amenities of the 

 time and to have recommended that he be 

 awarded the Ph.D. The omission of any 

 acknowledgment to indi\4duals or to in- 

 stitutions could have been an understandable 

 oversight in his haste to test the action of 

 follicular fluid on the vaginal epithelium 

 of the mouse, or it could have been a device 

 for avoiding any embarrassment. It is a 

 coincidence that 15 years later in an office 

 at Brown when a younger colleague was 

 threatening to look into the problem of the 

 hormonal control of mating behavior, Allen 



asked in his characteristically friendly way 

 and also somewhat paternally, ". . . why 

 don't you return to your woi-k on the 

 epididymis?" 



With hurdles of the thesis and its publica- 

 tion iK^iind him, and the conviction that 

 the follicular fluid contains the substance 

 he was seeking, he must have thought of 

 injecting follicular fluid from the large 

 follicles of the sow (he had seen them at 

 Brown) into ovariectomized mice and ex- 

 amining the vaginas for the sequence of 

 changes he had described in intact mice. 

 It is clear that the idea was not suggested 

 to him by anything he read. As he often 

 said jocularly, we did the work first and 

 looked up the literature later. The published 

 statement to this effect (J. Biol. Chem., 

 61: 711-727, 1924) was somewhat qualified 

 but almost as direct, ". . .we paid but little 

 attention to the papers of the various 

 workers who have claimed to have demon- 

 strated active preparations until after our 

 own first definitely positive results were 

 obtained." An unconventional approach, 

 but excuseable perhaps when the hunch is 

 as "logical" as it was to Allen. 



By the early spring of 1923 he had made 

 promising preliminary tests and a few days 

 before Charles Danforth left Palo Alto for 

 the Anatomists' meetings in Chicago, he 

 received an exultant telegram saying that 

 he (Allen) had succeeded in inducing estrus 

 in a spayed mouse by injecting follicular 

 fluid. Others had come close to the dis- 

 covery, but the reason they failed was that 

 no one had had a clear-cut practical test. 

 Danforth is the authority for saying that 

 the ideas back of all this were Allen's, 

 but in order to obtain a purified product of 

 the active hormone in the liquor folliculi 

 he was using, he enlisted the cooperation of 

 Edward A. Doisy whose laboratory was in 

 an adjoining building. Time has made it 

 clear that Doisy was undoubtedly the most 

 capable collaborator Allen could have found 

 anywhere for this kind of research. 



A side of Allen that ingratiated him to all 

 was seen at the time of the first announce- 

 ment of the discovery of the action of 

 follicular fluid on the vagina and is quoted 



