Welcome to the fourth installment of our series chronicling the history of the birth control pill. In the previous installment, progesterone, the birth control pill’s active ingredient, could only be administered intravenously. Scientists working in Mexico figured out how to alter its chemical structure so that progesterone would be active when taken orally.
Katharine McCormick was born into a moneyed family and was, in 1904, the second female graduated by the Massachusetts Institute of Technology. After receiving her degree in biology, she married a wealthy man, but shortly into the marriage she gained control of her husband’s estate due to his illness. She put a lot of this money to good use: In the 1920s, she aided Margaret Sanger’s efforts to smuggle diaphragms into the country.
Katharine McCormick, a philanthropist and one of the first scientifically trained women, provided early funding for the Pill.
Her involvement with Sanger didn’t end there; indeed, both Sanger and McCormick had a lot in common, despite Sanger’s working-class childhood and McCormick’s privileged upbringing. According to historian Elaine Tyler May, McCormick and Sanger both had “a tremendous faith in the possibility of science,” and Sanger “believed that science held the key to contraception and to women’s emancipation.” Back in the ’20s, Sanger wrote:
Science must make woman the owner, the mistress of herself. Science, the only possible savior of mankind, must put it in the power of woman to decide for herself whether she will or will not become a mother.
In 1950, McCormick again joined forces with Sanger. In the mid-’40s, after a countrywide tour of family-planning clinics, Sanger had come to the conclusion that the diaphragm was not an adequate form of birth control, revitalizing her hope for a “magic pill.” Neither pharmaceutical companies nor the government wanted to invest in contraceptive research, considering it a “disreputable” area of study, so Sanger hatched a scheme to bankroll the independent development of an oral contraceptive. At Sanger’s behest, McCormick provided the lion’s share of funding for the project — more than $2 million (compared to the value of a dollar in the year 2000, that would be about the equivalent of $12 million). Sanger and McCormick tapped Gregory Pincus to conduct the research. McCormick, thanks to her education in biology, oversaw the research in addition to funding it.
In the 1930s, while a professor at Harvard, Pincus was the first to fertilize a rabbit’s ova in a test tube, a technique that later formed the basis for in vitro fertilization. At the time, this was considered morally outrageous and, although Harvard recognized his achievement as one of the most significant in its history, Pincus was denied tenure in 1936.
After that debacle, Pincus became an independent researcher. He and colleague Min-Chueh Chang experimented with synthetic progesterone, hoping to discover a cure for infertility. In their initial experiments, Pincus’ lab used progesterone synthesized by Russell Marker’s method. They confirmed previous experiments on small mammals, but found that large doses of progesterone were required to inhibit ovulation.
In 1952, Pincus encountered Harvard gynecologist John Rock, who was engaged in experiments with progesterone — also with the goal of treating infertility. While Pincus was experimenting on rabbits, Rock was already conducting trials on humans. Rock’s treatment involved blocking ovulation for two years, under the hypothesis that a period of “rest” would lead to a “rebound” that would jump-start fertility. Because preventing pregnancy wasn’t the purpose of his treatment, he was able to skirt Massachusetts’ legal ban against the distribution of information about birth control. Many of Rock’s patients suffered from irregular periods, and once on the experimental therapy many became convinced they were pregnant, as the side effects mimicked pregnancy. Pincus suggested that instead of administering hormone therapy daily, it be administered for 21 days with a seven-day reprieve, allowing the subjects to experience regular menstruation. The benefit of this would be twofold, as patients would have regular periods and also be disabused of the notion that they were pregnant.
In any case, Pincus was shocked to find out that, for all intents and purposes, a hormonal contraceptive was already being tested on human subjects. Still, the drug needed to be tested as a contraceptive, rather than as a treatment for infertility.
However, the dilemma of potency still remained — the drugs were being injected intravenously at high doses, and weren’t yet effective when administered orally. This dilemma was solved by the independent discoveries of Luis Ernesto Miramontes of Syntex and Frank Colton of Searle, who had synthesized a variety of progesterone that was effective in pill form. These drugs were intended as “menstrual-cycle regulators,” but it seemed to Pincus that a contraceptive pill’s chemical structure had already been produced by other scientists, none of whom had appreciated its contraceptive potential. Pincus’ lab tested these compounds on rabbits and rats, evaluating their effectiveness and safety. With successful animal testing under his belt, Pincus set his sights on testing progesterone as a contraceptive in humans.
Pincus sought a gynecologist to co-lead the clinical trials, and chose John Rock. Despite her Catholic background, Sanger objected to this choice, thinking a Catholic “would not dare advance the cause of contraceptive research.” McCormick, however, approved of him, believing that he could keep his scientific pursuits separate from his religious beliefs; Sanger eventually came to look highly upon him as “[a] good R.C. and as handsome as a god.” Rock’s Catholicism probably also helped mitigate the scandalous nature of their research, if ever so slightly. Pincus, in fact, had ruled out working with a fellow Jew, believing that such a partnership would further stigmatize his research. Rock and Pincus masked their early clinical trials under the cover of Rock’s research into infertility. These preliminary tests led to large-scale field trials.
Stay tuned for our next installment of this series, in which clinical trials for the birth control pill — the largest at the time — are undertaken.