- 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
Marker’s sudden departure dealt a hard blow to Syntex, for he took with him all his notes on the synthesizing process; but the firm quickly recovered. It recruited George Rosenkranz from a Havana pharmaceutical firm—and Rosenkranz promptly reconstructed from published Marker papers, and his own research experience, the Marker process. In 1949 the firm also recruited a Viennese, Carl Djerassi, whose research genius was of the same order as Marker’s. Syntex’s progesterone production grew exponentially, with a proportionate drop in price. The hormone was sold for eighteen dollars a gram in 1945; in 1952, Syntex sold ten tons of it to a single company, Upjohn, for only forty-eight cents a gram.
For Pincus’ purpose, however, this synthetic hormone was no better than the other kind, since it was ineffective when taken by mouth. Not until 1952 did Djerassi report his synthesis of a type of progesterone which—when tested on rabbits, guinea pigs, monkeys, and finally, three women suffering from grave menstrual problems, at the National Institute of Child Health and Human Development in Bethesda, Maryland—proved to be immensely more potent (by a factor of ten or more) than the natural hormone, whether injected or orally administered. It was called norethindrone; and simultaneously with its public announcement Syntex applied for a patent on it. Three years later, or nineteen months after a full report of Djerassi’s work had been published in the American Chemical Society’s Journal , G. D. Searle of Chicago filed for a patent on a close isomer of norethindrone which Searle’s Frank Colton had allegedly developed in work wholly independent of Djerassi’s. Called norethynodrel, it proved orally effective, and in due course, it, like Syntex progesterone, received full patent protection.
Searle and Syntex were of course on the list of companies to whom Pincus addressed his letters of inquiry; and when he received, in prompt response, consignments of fifteen different progestational compounds, Searle’s norethynodrel and Syntex’s norethindrone were among them. Moreover, of all the fifteen these two proved most effective in the tests Chang soon made of them on laboratory animals. The two were then tested, in cooperation with Rock, on volunteer women, employing the same regimen that had been used with natural progesterone—a pill a day for twenty days beginning on the fifth day of the cycle. It was found that a mere forty milligrams of norethindrone, or a mere twenty of norethynodrel, as compared with three to four hundred of natural progesterone, sufficed effectively to prevent ovulation.
Now came the final, most daring phase of Pincus’ enterprise—the phase in which his personal qualities and energy became indispensable to the project’s success. Called into full exercise were his stubborn optimism, his drive, his ability as an organizer, his capacity to inspire a research team with a sense of mission, and (perhaps most important of all) his supreme self-confidence and consequent willingness to take chances that a less confident man would not have risked.
While the tests of synthetic progesterone were being completed, there impended a conference (the fifth) of the International Planned Parenthood Federation, a world body founded by Margaret Sanger in 1952. It was to be held in Tokyo in late October, 1955. Pincus proposed to Rock that the two of them attend it and present to the assembled delegates, and to the world press, a report on the work in progress. Rock demurred, emphatically: the test results thus far, though encouraging, were far from conclusive; the conference was in essence a propaganda forum for birth control; and any scientist who there talked hopefully of developing a contraceptive pill would make world headlines at grave risk to his professional reputation. Rock not only refused to go, he urged Pincus not to go either. Pincus went all the same, accompanied by Chang, their ways paid by Mrs. McCormick. Both men presented papers. Chang’s was simply a review of possible ways in which a physiological contraceptive might someday be developed. It mentioned hormone-level manipulations as one of the ways but stressed that too little was known about “the basic mechanisms of … reproductive physiology” to enable scientists to proceed as yet in other than a “hit or miss” fashion. Pincus, on the other hand, having presented the results of the tests he and Chang and Rock had made of norethindrone and norethynodrel, boldly inferred from these that the “delicately balanced sequential processes involved in normal mammalian reproduction” could be disrupted “in such a way that no physiological cost to the organism is involved.” This, he said, was the objective of the Worcester Foundation’s work and would “undoubtedly be attained.“” His implication, which attracted world press attention, was that the attainment would be soon.
Thus did Pincus make sure that there would be adequate funding, mostly from Mrs. McCormick, for what was bound to be by far the most expensive as it was the most risky part of the entire undertaking—the conduct of field trials with thousands of women, and dozens of professional people.