The Birth of the Pill: How Four Crusaders Reinvented Sex and Launched a Revolution (35 page)

Jack Searle was a short, slender man with wire-rimmed glasses. Though he looked like a Midwestern conservative,
at heart he was a risk taker
, and he reinvested his company’s profits in state-of-the-art laboratories and manufacturing plants, urging his research directors to be aggressive and come up with more new drugs. No doubt that’s why Searle hired men like Pincus, scientific gamblers who lost more often than they won. Jack Searle knew that it took only one big product to change the fortunes of a corporation. He’d seen Smith, Kline & French, one of his competitors, double its sales with the discovery of the new tranquilizer Thorazine. Another competitor, E. R. Squibb & Co., reported that nearly half its sales were coming from products introduced in the past five years, including Nydrazid, an antibiotic used to treat tuberculosis. The drug industry was booming in the 1950s. Americans were spending like never before on their health, and each year brought a new array of so-called wonder drugs. And no drug company in the country was pouring
a higher percentage of its revenue
back into research than Searle. Jack Searle was determined to hit it big.

Even though it had not scored a huge hit since Metamucil, Searle was getting along nicely, with earnings of $6 million
on sales of $26 million in 1955
. Its stock was rising, and the family was grooming a new generation of leaders. The next wave included
Sue Dixon’s husband, Wes
, who was appointed an executive vice president in charge of foreign markets in January 1956. It also included Sue’s two brothers, Dan (who would go on to become the company’s president when Jack Searle retired) and Bill (who would become the director of sales and marketing). But Sue Dixon, despite her college degree and sharp intellect, was not being groomed for a job in the company. In part that was because she was pregnant for a good part of the 1950s, but that wasn’t the biggest reason. The biggest reason was that she was a woman, and even women who were unmarried and childless were seldom considered for high-level corporate jobs. That much became obvious to Sue Dixon even when she chose a college and a major. Her brothers were encouraged to study medicine and business; she was pushed into fine arts.

Had she considered trying for a career in science or business, given her family’s work?
“Me?”
she asked. “Women didn’t work.” Even her fine arts degree proved to have little practical use. She gazed across the living room at her husband and smiled. “I wanted to be a great commercial artist, but that all went down the drain with Wes Dixon!”

Marriage and motherhood ended any chance she might have had for a career, but Sue Dixon nevertheless had an advantage over many of her friends and peers. After giving birth to her first two children, she was able to take time before getting pregnant again, largely because her marriage coincided with the work Pincus was doing for her father’s company.

Jack Searle liked the fact that his company was still small enough for the chief executive to be involved at every level. He trusted his research men, Al Raymond and I. C. Winter, but he still liked to sit in on their meetings and ask questions of the chemists and biologists in the room.

Despite their radically different backgrounds (Jack Searle grew up in prosperity and liked to hunt and play golf), he and Pincus got along well. Both men were calm, confident, and bold. At one point in the early days of clinical trials, Searle flew to Puerto Rico with Winter to meet Pincus and Rock and see firsthand how the pill was changing lives. Dr. Garcia said Searle immediately
grasped the pill’s “sociological implications”
and became a champion for the cause. Even before his company began selling the pill, Jack Searle donated money to
the cause of population control
.

Searle had many reasons to continue pushing the pill toward the market. He had a jump on the competition, which meant the pill, if all went well, might earn a great deal of money. He also believed that this medicine, whatever its flaws, would be a force for good, that it would help women and help the planet.

He was still a business executive, though, which meant balancing risk and reward. On the risk side, there was Dr. Rice-Wray stating publicly that the side effects were too great for this pill to be widely administered to women; there were the scientists who said it would require at least five years of testing to be certain that a daily pill for healthy women would not have long-term, unforeseen dangers; and, of course, there was the Catholic Church, which had already made it clear that it would oppose the use of any such contraceptives.

In the end, Jack Searle decided to go ahead—cautiously.

By 1957, Pincus was preparing an important scientific paper for the
American Journal of Obstetrics and Gynecology
on the results of his human trials in Puerto Rico, which would lend credibility to the cause and take the pill a step closer to reality. Searle encouraged him to proceed. But to be careful, he advised Pincus that it would be best to
omit the company’s name
from the paper.

TWENTY-SEVEN

The Birth of the Pill

A
FTER THE MEETING
of scientists in Skokie, Pincus and Searle once again tinkered with the makeup of their drug, which was now being referred to among team members by its trademarked name, Enovid (pronounced eh-NAH-vid). Pincus had a simpler name. He called it The Pill, as if it were the only one that mattered. There was no such thing as The Soap or The Vacuum or The Car, but this product was beginning to earn a special identifier in his and others’ minds because its tablet form so sharply differentiated it from any contraceptive device that had come before. This wasn’t merely an incremental improvement; this was a radical reinvention, and it was exactly what women needed. This was
the pill
, the one they’d been waiting for, the one that changed everything.

By 1957, Pincus and Rock both felt confident that the pill worked and worked safely. Their biggest challenges were to get more women to try it and, at the same time, see if they could do something to reduce the severity of the side effects.

Pincus wasn’t as worried as Rice-Wray about how much women were suffering. Some people involved in the Puerto Rican trials attributed the reactions among women in San Juan to the “
emotional super-activity of Puerto Rican women
,” and Pincus continued to believe—or hope—that many of the side effects were merely psychosomatic. To test that theory, he designed a simple experiment. He took one group of women and gave them Enovid with the usual warnings about possible reactions. He took another group and
told
them they were getting Enovid but gave them a placebo instead—along with the same warnings on side effects that he’d given the first group. He also told members of this group that they should use an additional form of birth control to be certain they didn’t get pregnant. The third group received the real Enovid and no warnings about side effects.

The first group reported side effects in 23 percent of their cycles. The second group, which received placebos that could not have possibly caused any reactions whatsoever, reported side effects in 17 percent of their cycles. The third group—women taking Enovid with no warnings—experienced side effects in only 6 percent of cycles.

Pincus’s experiment violated two basic rules of modern medical research. His patients were not informed of the purpose of the study, nor were they warned of the risks. But the results nonetheless further convinced him he was right—many of the side effects were imaginary, the results of expectation and fear.

Reassured, Pincus set out to recruit more women.

Clarence Gamble, the eugenicist who had been sponsoring research in Puerto Rico for years, offered to fund a second trial. He connected the Pincus team with the medical director at Ryder Memorial Hospital in Humacao, a city thirty-five miles from San Juan on the east coast of Puerto Rico. Gamble had been working with the hospital for more than twenty years. Earlier that same year, he had donated a cautery machine, which was used to perform sterilizations, and donated money to
train a doctor in how to use it
. He also donated a red Jeep so that hospital workers could navigate the muddy, mottled streets of Humacao as they visited patients.

The job of testing Enovid at Ryder Hospital fell to Dr. Adaline Pendleton Satterthwaite, the only obstetrician-gynecologist on staff. Like Dr. Rice-Wray, Dr. Satterthwaite was an American-born woman who had come to Puerto Rico as a religious missionary. At Ryder, she delivered about six hundred babies a year. She learned quickly after arriving in Puerto Rico that many pregnant women came to the hospital for two reasons: to have their babies and, immediately afterward, to get sterilized. “
O, doctora, opéreme
,” they would tell her. If not for the incentive of sterilization, Satterthwaite said, most of the women would have delivered at home with midwives. Still, Satterthwaite often refused. Unless the women had three or more children and the consent of their husbands,
she would not sterilize
. Instead, she would teach them to use a diaphragm.

Now, to test the pill, she chose an area of Humacao called La Vega, which Gamble described as “the most impressive” slum he had ever seen, with no toilets or sewers and housing so crowded there was
scarcely room “for a squeezed pedestrian.”
Gamble hired a woman to take a census of La Vega, going door to door and asking mothers how many children they had, whether they were sterilized, and what type of
birth control they were using, if any
. Satterthwaite began recruiting in La Vega as well as offering Enovid to the women who had been denied sterilization at the hospital.

She had no trouble finding willing patients, but once again, side effects complicated the work. Women complained of breakthrough bleeding, nausea, and headaches. In examining her patients, Satterthwaite noticed another cause for concern: Women taking the pill for several months appeared to be suffering inflammation of the cervix, the part of the womb whose tip projects into the upper area of the vagina. The inflammation wasn’t necessarily harmful, but it might have caused bleeding in some patients. “Whatever you call it,” she observed, “
the cervix looks angry
.”

Still, women desperate to avoid pregnancy continued to enroll in the studies. With trials now underway in two Puerto Rican communities, Pincus and his team began work on a third location in Port au Prince, Haiti. The increasing numbers of patients gave Pincus and Searle hope that they might soon have enough information to prove Enovid’s safety.

Meanwhile, Pincus continued experimenting with different dosages and chemical variations, aiming to reduce the side effects. He tried putting a small amount of antacid in each pill, but it wasn’t clear if it made any difference. At one point, Pincus and Chang discovered that Searle’s compound had accidentally been contaminated with a tiny amount of synthetic estrogen, also known as mestranol. All along, Pincus had been sticking with progesterone and trying to avoid using estrogen because it was known to cause cancer, and he was worried about the long-term effects of its use. His assumption had been that progesterone was safe for women but that estrogen might not be. When he learned of the accidental contamination, Pincus ordered the drug company to get rid of the estrogen, not only because he thought it might be unsafe but because he thought the estrogen might have been responsible for some of the side effects. But when Searle sent the pure form of Enovid to Puerto Rico, the results were a surprise. Not only did the nausea persist, women began experiencing even more breakthrough bleeding.

Now it dawned on Pincus that the accidental contamination might have been a good thing. With more experimentation, he found that breakthrough bleeding increased when the estrogen dose fell, and nausea and breast pain increased when it rose. He also discovered that when the estrogen levels were too low, the pill was less effective in preventing pregnancy. Now, instead of purifying the pill, he suggested that Searle intentionally make its ten-milligram tablets with 1.5 percent mestranol, which seemed to Pincus like it might be the sweet spot. The side effects did not disappear completely, but they were reduced, and the bleeding all but stopped.

They would stick with this one.

Still, in the first months of 1957, dropout rates remained high and the number of women enrolled in the study low—too low, Pincus believed, to win FDA approval.

Pincus knew he would never be able to test the pill on tens of thousands of women. Even thousands looked like a stretch. But there was no benchmark, no solid number that he knew he would need to get FDA approval. So to make his studies sound more impressive, he stopped talking about the number of women participating in trials. In fact, he stopped talking about women altogether. Instead, he talked about the number of menstrual cycles observed in the experiments. “
In the 1,279 cycles
during which the regime of treatment was meticulously followed,” he wrote in one study, “there was not a single pregnancy.”

Pincus wasn’t the first to employ this trick. Drug companies often used so-called life-tables to analyze data for drugs that were continually used, arguing that the length of time and the number of doses taken mattered more than the number of people taking them. Given that Pincus couldn’t openly test his pill in the United States and continued to have problems finding adequate numbers of women in Puerto Rico, the switch in measurement standards made a difference. Simply put, 1,279 menstrual cycles sounded more impressive than 130 women.