- Historic Sites
The Story Of The Pill
How a Crash Program Developed an Efficient Oral Contraceptive in Less Than a Decade
August/September 1978 | Volume 29, Issue 5
Within a few years thereafter each of the hormones had been proved by laboratory analysis to be not a single substance, but a family of compounds whose chemical structures are very similar (there are in fact some twenty estrogens); and both estrogen and progesterone were being manufactured commercially from such source material as pigs’ ovaries and human urine. The manufacturing process was elaborate and time-consuming. The living body easily makes steroids (fat-soluble compounds, including all the sex hormones) out of cholesterol, but laboratory chemistry can do so only with difficulty—and alternative sources of raw material which could be more easily processed had not yet been discovered. Hence the production costs and unit price of estrogen and progesterone were very high and the supply severely limited, while the market for them swiftly grew. Estrogen had been found effective as a medicine for dysmenorrhea (painful menstruation) and irregular periods. Progesterone was in demand for women who were deficient in this hormone and consequently “chronic aborters.” And both hormones were needed in growing quantity by scientists for laboratory studies of mammalian reproduction.
Early in the 1930’s Gregory Pincus made a name for himself, not only among scientific colleagues but also with the public at large, when he managed by chemical and mechanical means to cause unfertilized rabbit eggs to grow and divide in test tubes, thereby producing rabbits having mothers but no fathers. Sensationalized reports of this appeared in the press, and there ensued much popular excitement about the possibility of producing human babies in the same way, though Pincus himself emphatically disavowed any intention of experimenting toward that end. In 1936, the year in which he published The Eggs of Mammals , a classic in its field, he was experimenting with the ways in which progesterone operates to facilitate implantation. He was also studying the effect of estrogen on ovulation in mated rabbits (rabbits do not ovulate unless mated).
Simultaneously, of course, as part and parcel of his own work, he kept close tabs on the reported experiments and hypotheses of others laboring in his field. He read Carl C. Hartman’s highly influential Time of Ovulation in Women (1936), wherein conclusions about the role of hormones and the endocrine system in human reproduction were boldly drawn from recent research results. It is highly probable that he read a paper entitled “The Prospects for Hormonal Sterilization” by Columbia University gynecologist Raphael Kuzrok, a paper published in 1937 wherein Kuzrok speculated about the possibility of using sex hormones to prevent ovulation. It is certain that Pincus read, in that same year, a paper by A. W. Makepeace, G. L. Weinstein, and M. H. Friedman of the University of Pennsylvania reporting an experiment in which progesterone was administered to mated female rabbits, with the result that the rabbits did not ovulate. This greatly impressed him: fourteen years later he was to make a duplication of the reported experiment the starting point for his work toward the Pill.
Meanwhile, Pincus faced a major crisis in his personal life; his professional career was in jeopardy. That he had done brilliant work at Harvard, none could deny. When the university issued a pamphlet in 1936 as part of its tercentenary celebration, Pincus’ parthenogenic rabbit was cited in it as one of the outstanding scientific achievements of the institution’s three hundred years. Hence the total unexpectedness of the blow dealt him by the university less than a year later. He was then notified that he would not be promoted to associate professor at the end of his second three-year term as assistant professor, which meant, by the administrative rules then in force, his dismissal from Harvard’s faculty the following year. It was perhaps fortunate for his emotional equilibrium that a prior arrangement enabled him to spend the last year of his Harvard appointment in Cambridge, England (he worked in the Strangeway Laboratory there), rather than in Cambridge, Massachusetts. Certainly it was fortunate for his career that his friend, Hudson Hoagland, who had become chairman of the biology department at Clark University in 1931, was, in his own words, “incensed” by Pincus’ dismissal. Hoagland was convinced, as he wrote later, “that academic politics, including some antisemitism [and] jealousy toward Pincus on the part of some… were the reasons for his discontinuance.” There was nothing passive about Hoagland’s indignation. When no other position was opened to Pincus in America as the year wore on, Hoagland obtained private funds to bring him to Clark as a “visiting professor” in 1938.