Carl Djerassi with his assistant, Arelina Gonzalez, 1951

Welcome to the third installment of our series chronicling the history of the birth control pill. In the previous installment, we learned about the iconoclastic chemist Russell Marker, who figured out how to synthesize large quantities of progesterone — the birth control pill’s active ingredient — from a yam called barbasco that grew wild in Mexico.

In 1949, Russell Marker dropped out of science — “I considered all chemists to be crooks,” he bitterly opined — and a scientist named Carl Djerassi was hired to head the lab at Syntex, the hormone-synthesizing laboratory in Mexico that Marker had co-founded in 1944. Within a few years, Syntex was a major player on the synthetic-hormone scene in Europe and the Americas.

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After Luis Miramontes’ successful experiments, all of the elements for Sanger’s “magic pill” were in place.

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Although progesterone could be manufactured in large quantities at this time, it could only be given intravenously. Progesterone was being used therapeutically to prevent miscarriage and treat excessively heavy menstrual periods. The lack of alternatives to injections represented a problem for these people — a daily pill would be easier and more convenient than frequent injections. In 1950, Syntex set their sights on the development of a synthetic form of progesterone that was more effective in smaller doses and could be administered orally rather than by intravenous injections. Such a development would be necessary before Margaret Sanger’s dream of a “magic pill” could come true.

Djerassi found a scientific article from 1944 that described a seed extract called strophanthidin, which made progesterone more potent when taken orally. Strophanthidin was chemically similar to progesterone; it just lacked a carbon atom. The experiments described in the article were inconclusive, so Djerassi decided to perform followup experiments. He attempted to rearrange the yam-derived progesterone to resemble the seed-derived molecule described in the paper. When the resulting substance was injected into rabbits it was found to have four to eight times natural progesterone’s potency.

Additionally, in pre-WWII Germany, a scientist had introduced a gas, acetylene, into one of the rings of an estradiol molecule, which converted it into a chemical that remained stable when taken orally. This could also help chemists create a form of progesterone that could be administered by pill rather than by syringe.

Luis Ernesto Miramontes

Luis Ernesto Miramontes, working at Syntex, was tasked to find an oral replacement for progesterone injections. By 1951 he had done so. Miramontes and Djerassi tested it, first on nonhuman animals and then on human subjects who suffered from excessively heavy menstrual periods. The new compound seemed hugely successful — when administered orally, it was eight times more potent than the progesterone synthesized by the body. A vehicle for Sanger’s “magic pill” had been discovered. It was called norethindrone.

Neither Marker nor Djerassi had envisioned anything resembling Sanger’s dream for a pill that would put women in charge of their own reproductive destinies, a pill that could be manufactured cheaply and made accessible worldwide. The scientists were mostly interested in the challenges involved in basic research. But thanks to researchers’ work over the first half of the 20th century, all of the elements for Sanger’s “magic pill” were in place: Progesterone was known to inhibit ovulation, it could be synthesized cheaply, and it could be taken orally. These disparate threads did not come together, however, until Sanger teamed up with a wealthy benefactor.

Stay tuned for the next installment of this series, in which Margaret Sanger and Katharine McCormick conceptualize and bankroll the development of the hormonal birth control pill.