America and the Pill: A History of Promise, Peril, and Liberation (4 page)

The combined efforts of these and other individuals working

in various settings and capacities led to the discovery of the syn- thetic hormonal compound that suppressed ovulation. Pincus tested the compound on laboratory animals, but he couldn’t conduct any clinical trials on humans. For this, the collaborators turned to Harvard-trained obstetrician and gynecologist John Rock, who was the director of Brookline’s Reproductive Study Center. Rock and Pincus were both involved in research for treatments for infertility. Reproductive medicine was an expand- ing field in the 1950s. Infertile couples struggled in the midst of the baby boom, when it seemed as though everyone was procre- ating. Many clinical researchers who became involved in the development of the pill also sought cures for infertility. These physicians were interested in family planning. As one explained: “Every child should be a wanted child. Those who want them should be able to have them; those who don’t should be able to prevent them.”
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John Rock was among the physicians who worked on both fertility and contraception. Like Sanger and McCormick, Rock had a powerful independent streak that led him to defy

religious, legal, and cultural taboos. The grandson of an Irish immigrant tailor and son of a liquor store owner, Rock grew up with a spirit of adventure and risk taking. In high school he won a scholarship to travel in South America, and he began his work life on a banana plantation in Guatemala. Rebelling against his boss in Guatemala and then against his father, who wanted him to become a businessman, Rock entered Harvard College and pursued a career in medicine. He grew up true to his Catholic faith but with a strong belief that his conscience should be his most important guide in life.
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Rock became one of the pioneering physicians in the field of reproductive medicine, working on both infertility and contra- ception. A practicing Catholic and a social conservative, he be- lieved that in certain circumstances birth control was medically necessary, but only when there were particular health reasons to avoid pregnancy. Highly critical of routine use of birth control, he held “no brief for those young or even older husbands and wives who for no good reason refuse to bear as many children as they can properly rear and as society can profitably engross.”
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But Rock took issue with the Catholic Church’s prohibi- tion against birth control, because it prevented physicians from acting in what they believed to be their patients’ best interests. In the 1940s, he taught students at the Harvard Medical School how to fit patients with diaphragms—a bold move for a Catholic doctor in a state that outlawed the distribution of birth control information and devices. He advocated the lifting of legal restrictions that hindered physicians from providing patients with contraceptives. Later, he clashed openly with the Church, arguing that the pill was consistent with Catholic pre-

cepts. Rock insisted that it was not an “artificial” means of birth control because the hormones in oral contraceptives mimicked those that occurred naturally in pregnancy.
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Rock agreed to work with Pincus to test the potential for the hormone progesterone to inhibit ovulation in humans. Now all they needed was the essential ingredient: women who would volunteer for the studies. Rock found sixty volunteers. Some of the women who joined the clinical trials were infertil- ity patients at the Free Hospital for Women; other volunteers were nurses at the Worcester State Hospital. The complicated procedure included daily basal temperature readings, vaginal smears, and urine collection as well as monthly endometrial biopsies. The results were promising: The drug apparently in- hibited ovulation. But there were problems with the study. The numbers were too small, and only half of the women complied with the rigorous protocol. The challenge was to find a large group of volunteers who would be motivated to comply.

Katharine McCormick was frustrated by the difficulty of finding an adequate pool of volunteers. “The headache of the tests is the cooperation necessary from the women patients. I really do not know how it is obtained at all—for it is onerous— it really is—and requires intelligent, persistent attention for weeks.”
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She was eager to begin a major clinical trial but daunted by the challenge of finding women willing to participate.

Lacking access to volunteers, researchers turned to involun- tary subjects. In one of the most disturbing episodes in the de- velopment of the pill, Pincus forced fifteen psychiatric patients at the Worcester State Hospital to participate in trials that would afford them no benefit. Unlike the women in Rock’s

earlier study, most of whom were infertile and eager to test the pill’s potential to temporarily suppress ovulation, thus possibly stimulating the ovaries when the drug was withdrawn, the psy- chiatric inmates were neither at risk of pregnancy nor hoping to become pregnant. Experimental programs involving coer- cion were used to test other drugs as well at the time, before professional standards prohibited such practices. Nevertheless, because the pill was tested on physically healthy women who had nothing to gain by participating in the study and possibly a great deal to lose in terms of unknown risks and side effects, serious ethical questions have been raised about these tests.
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Critics have long faulted doctors, scientists, and pharmaceu- tical companies for exposing women to dangerous tests of high- dose hormonal contraceptives. While there were certainly some clear cases of abuse and unethical practices, such as the coercive studies using psychiatric patients, the testing of the pill largely conformed to the standards of the day and often exceeded them. At the time there were few regulations in place for the testing of drugs. Compared to other countries, the United States had relatively stringent requirements for gaining govern- ment approval because of FDA regulations. But it was not until 1962 that doctors were required to inform patients if the drugs they prescribed were experimental. Standards of informed con- sent for the testing of drugs were in the distant future.
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Although progesterone and estrogen had been administered to women for decades to treat gynecological disorders and pre- vent miscarriages, finding a large enough volunteer group to test the contraceptive effectiveness of these hormones presented a major challenge. The laws against contraception in Massachu-

setts, where small initial trials had been conducted, ruled out that state as a site for a large study. John Rock had previously studied the pill for its “rebound effect” to encourage fertility, with the hope that after an infertile woman stopped taking the pill, she would then start ovulating and become pregnant. That research did not violate any laws. But Rock knew that if he tried to test the drug as a contraceptive, he could face criminal charges resulting in steep fines and imprisonment.

So the researchers considered several other possible sites for a study, within the United States as well as outside the country. Katharine McCormick worried about finding a stable popula- tion of willing and cooperative volunteers. “Human females are not easy to investigate as are rabbits in cages,” she noted. She was concerned that if the women did not stay in one place to allow for adequate follow-up exams, or if they did not take the pills consistently, “the whole experiment has to begin over again—for scientific accuracy must be maintained or the re- sulting data are worthless.”
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In 1956, Rock and Pincus finally decided to conduct the first large-scale clinical trials in Puerto Rico. The island ap- peared to be an ideal setting for several reasons: No laws pro- hibited contraception, and in fact, there was already an established network of sixty-seven birth control clinics on the island. With more than six hundred people per square mile, Puerto Rico was one of the most densely populated areas of the world. Impoverished women living in crowded, disease- ridden conditions were desperate for birth control. At the time, the only option available to them for reliable contraception was sterilization, which had been vigorously promoted and was

widespread on the island, due in large measure to funding from the wealthy eugenicist Clarence Gamble, a longtime advocate of sterilization of the poor. Puerto Rican women wanted a nonsurgical, reversible, and effective means of preventing preg- nancy. Women who volunteered for the studies were given pills containing 10 milligrams of progesterone and small amounts of estrogen, many times greater than the pills on the market today. But at the time researchers were uncertain whether lower doses of hormones would be effective, and they wanted to be sure that the pill they tested would prevent pregnancy.
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In Puerto Rico, two women conducted the on-site trials, Dr. Edris Rice-Wray and Dr. Adaline Satterthwaite. Rice-Wray, a faculty member at the Puerto Rico Medical School and direc- tor of the Public Health Department’s Field Training Center for nurses, was medical director of the Puerto Rican Family Planning Association. Working with Pincus and Rock, she set up a research site in a suburb of San Juan. Satterthwaite, who like Rice-Wray was born and trained in the United States, es- tablished a trial site in Humacao, a rural area. The women they recruited were eager to participate. Already saddled with large families, many were in poor health and malnourished, longing for an effective yet reversible contraceptive. So many women volunteered that some sites resorted to waiting lists.

The developers of the pill were particularly concerned about its safety. They put in place elaborate precautions to monitor the health of the women who took part in the trials, such as frequent medical exams and lab tests. Study partici- pants in impoverished areas received medical attention vastly superior to what was normally available to them. The re-

searchers were particularly sensitive to the effects of the pill because it was intended for healthy women. It was not a drug to cure a disease, which could have been tested on patients who were already sick. By the standards of the day, the studies were scrupulously conducted.

But there were serious problems with the trials. The high doses of hormones caused side effects such as nausea, headaches, and dizziness. In 1956, Rice-Wray reported that 17 percent of the participants complained of these symptoms. Even though the 10-milligram pill “gives one hundred percent protection against pregnancy,” she concluded that it caused “too many side reactions to be acceptable.” Rice-Wray tried to convince Rock and Pincus to end the study because of these problems, but they considered these symptoms to be minor and dismissed her concerns. Pincus claimed that many of the women’s symptoms were psychosomatic. He asserted, “Most of them happen because women expect them to happen.” But the side effects were real and serious, prompting many women to drop out of the study.
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Although women continued to volunteer for the studies, the investigators faced considerable hostility from suspicious offi- cials and the media. Local newspapers published false reports that a “woman dressed as a nurse” was distributing “sterilizers” and that “Nordic whites” were using “the coloured races as ‘guinea pigs.’ ” Priests and disapproving husbands also persuaded some women to drop out of the studies.
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Eventually, Rice-Wray and Satterthwaite were both forced to resign their positions. Yet there is no evidence that the researchers intentionally put women at risk. Women volunteered freely and enthusiastically.
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The women of Puerto Rico were not the only ones taking part in testing the oral contraceptive. Rock, Pincus, and their colleagues conducted studies in Haiti, Massachusetts, and New York City as well. Other researchers were also testing the pill at sites inside and outside the United States, including Ten- nessee, Seattle, Chicago, Los Angeles, Mexico City, Hong Kong, Australia, Ceylon, Japan, and Britain. The data collected from these trials contributed to the development of the com- pound that eventually received approval for marketing. After the drug was cleared in 1957 for the treatment of various gy- necological disorders, developers in the United States and Britain began the process of gaining permission to market the pill for use as a contraceptive.
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The approval process took place in several stages. The United States had a formal regulatory procedure; Britain did not. Nevertheless, Searle’s product, known as Enovid in the United States and Enavid in Britain, came on the market in both countries in 1957 as a treatment for infertility and men- strual disorders. Three years later Searle submitted a request that Enovid be allowed for use as a contraceptive. British au- thorities refused to discuss or even monitor Enavid for contra- ceptive use, insisting that the issue was too politically and morally sensitive. In the United States, the 1938 Food, Drug, and Cosmetic Act defined a drug not simply as something in- tended to treat a disease, but as a product “affecting the struc- ture or function of the body.” Under that definition, all contraceptives fell under FDA jurisdiction.

Government officials tried to distance themselves from the social and moral implications of the oral contraceptive by con-

centrating exclusively on safety concerns. As the FDA Deputy Commissioner wrote to a U.S. senator, “Although we recog- nize the presence of moral issues, they do not come within the jurisdiction of the FDA. Our consideration has to be confined to safety for intended use.”
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At the time, the FDA was over- whelmed with thousands of requests for approval of new drugs, with only a few regulators on staff. The application to market Enovid as a contraceptive was assigned to Dr. Pasquale DeFelice, a young obstetric gynecologist who was still completing his residency. Because of his lack of experience and the paucity of medical experts available within the FDA, the agency relied heavily on the advice of outside medical practitioners. In Feb- ruary 1960, the FDA wrote to seventy-five physicians at lead- ing medical schools around the country asking them to evaluate the safety of Enovid. Many responded positively, re- porting that they had found the drug to be safe and effective for short-term use in treating gynecological problems. But those reports were largely irrelevant to the question of the pill’s long-term use as a contraceptive.