The Birth of the Pill: How Four Crusaders Reinvented Sex and Launched a Revolution (20 page)

Marker was a maverick. He was prematurely bald, powerfully built, and chronically impatient. At twenty-three, just shy of earning his doctoral degree in chemistry, he’d quit because the University of Maryland had required him to take classes in which he had already earned a master’s degree. He couldn’t bear the thought of wasting his time. Without a doctorate, Marker bounced around the world of science, from the Ethyl Corporation (where he helped develop the octane-rating system for gasoline still used to this day) to the Rockefeller Institute. While at the Rockefeller Institute, he became interested in hormones. Marker observed that scientists were doing interesting work on hormones, but most hormones remained scarce and prohibitively expensive. The high prices stymied research. Progesterone at that time was so expensive that research scientists couldn’t afford to experiment with it at all. Even if the scientists could afford small amounts of the drug and even if their research led to fantastic breakthroughs, patients in need of the newly developed drugs would never be able to afford them. But Marker had a hunch that progesterone and other hormones could be made much more cheaply from vegetables. He mentioned this to his boss at the Rockefeller Institute, Dr. P. A. Levene, but Levene told him it had already been tried and hadn’t worked. Marker refused to accept such an abrupt dismissal. “I said it was a practical thing to work on and that if I couldn’t work on them at the Institute, then I would find
a place I could work on them
,” he recalled. He quit and accepted a position with Pennsylvania State College, taking a massive pay cut from $4,400 to $1,800 a year.

For a chemist, sex hormones such as progesterone and estrogen are relatively easy to manipulate, which is why they intrigued Marker. Sex hormones are steroids, organic molecules that share a common structure of carbon and hydrogen atoms arranged in four fused rings. Thousands of hormonal compounds have the same structure. The structure of progesterone, for example, is similar to that of testosterone. Their simplicity makes modification easy. With a few chemical steps, male hormones can be converted to female hormones and female hormones into male. New discoveries were coming rapidly as Marker began to dabble in this burgeoning field. At Penn State, he managed to make thirty-five grams of progesterone from the urine of a pregnant woman. At the time, doctors were beginning to treat women who suffered frequent miscarriages by giving them small doses of progesterone. The president of Parke-Davis, a drug company that helped finance Marker’s work, was thrilled, saying the company could sell Marker’s progesterone at a thousand dollars a gram. Marker soon figured out a way to do even better by making progesterone from bull urine. Meanwhile, other scientists found they could make sex hormones by modifying the chemical structure of cholesterol, although this method still proved expensive and time consuming. By 1940, Marker made a huge breakthrough and confirmed the hunch he’d had while working for the Rockefeller Institute, developing a five-step chemical process to produce progesterone from a compound found in the sarsaparilla root. His search for a plant that would yield even more of the key compound led him to Mexico and the
cabeza de negro
.

Soon scientists all over the world began manufacturing progestins (the term for synthetic versions of the natural hormone) and trying to improve on Marker’s work. Marker helped found a new company, Syntex, which quickly became one of the world’s leading suppliers of progesterone. But true to character, Marker soon became frustrated, saying he had never received his share of the profits generated from his work. When he quit, he destroyed all of his papers. His replacement, a Hungarian Jewish chemist named George Rosenkranz who had fled Europe during the war, struggled to replicate Marker’s work. Marker had been secretive about his methods and never even bothered to label the chemicals in his lab, relying on sight and smell to tell one from another. Within five years, though, Rosenkrantz not only matched Marker’s work but also worked out the synthetic production of androgens and estrogens. In 1949, Rosenkrantz recruited a young Austrian-born American named Carl Djerassi, who had left the University of Wisconsin to work in Mexico because he had heard that Russell Marker and
others were doing revolutionary work
there. Djerassi was determined to improve the company’s progestins.

For reasons not completely understood, synthetic progesterone was not particularly effective when taken orally. Injections were painful, and even those required larger doses than most other sex hormones. Djerassi set out to create a more potent progesterone that would work when taken orally. He remembered a paper he’d read in college describing how a chemist named Max Ehrenstein had removed a carbon atom from a molecule and replaced it with a hydrogen atom. To Djerassi, it was as if Ehrenstein “had transformed a very elaborate mansion . . . into a
funky little vacation house
.” It was a highly inefficient operation, but it gave him ideas. His modifications produced a new compound four to eight times more potent than the old ones. Perhaps best of all, his new compound was also able to survive absorption in the digestive tract, which meant it could be taken orally. Djerassi thought the new compound might be effective in helping women with menstrual disorders. He didn’t know that another young chemist—Frank Colton of G. D. Searle & Co.—had also been inspired by Ehrenstein to develop virtually the same thing. And neither Djerassi nor Colton knew that Gregory Pincus was searching for exactly such a compound.

“
Not in our wildest dreams
,” Djerassi said, “did we imagine that this substance” would one day become the active ingredient in a birth-control pill.

FOURTEEN

The Road to Shrewsbury

M
ARGARET SANGER AND
Katharine McCormick were counting on Pincus more than ever. Other researchers were exploring new forms of contraception, but most of the work involved sloppy stuff such as foams and jellies that did nothing to promote sexual spontaneity or pleasure. Sanger wanted a more precise instrument, something wholly new and groundbreaking. Yet so far neither McCormick nor Planned Parenthood had come up with enough money to capture Pincus’s full attention and ensure that he would see the research project through to the finish.

In May 1953, as Pincus and Rock were launching their first round of tests on humans, Sanger suggested that she and McCormick pay a visit to Shrewsbury to meet Pincus and see if he was someone McCormick might wish to support. McCormick wrote back that she would be delighted to make the trip. Her only request was that the journey be planned for a weekday, because, as she wrote, “I do not like to plan for any motoring on Sundays for it simply means waiting in a long line of cars, as
the crowds are so great
on that day.”

The meeting was set for June 8—a
hot and humid Monday
. McCormick’s chauffeur-driven Rolls-Royce glided through the rolling hills of central Massachusetts, past the sturdy working-class homes of Shrewsbury, and onto the macadam driveway of the Worcester Foundation.

The women were not put off by the utilitarian, cheaply furnished offices; the poor ventilation in the animal rooms; or the jerry-rigged appearance of the laboratories. If anything, they seemed captivated by the place’s scrappy charm, and they were especially enthusiastic about Pincus’s plan for testing John Rock’s patients. At one point, Chang heard McCormick whisper in Sanger’s ear: “
This is the place
.”

As the tour concluded that afternoon, McCormick asked Pincus how much money he needed. He had already negotiated a grant of $17,500 from Planned Parenthood to cover the first year of clinical trials, and Planned Parenthood had already turned to McCormick for help in paying for the work. McCormick had agreed to pay
half of the $17,500
.

Now, as she strolled the grounds of the Worcester Foundation, McCormick asked for the big picture. How much would it take to fund the entire research program? How much would it take to get her pill?

Pincus answered: $125,000.

McCormick nodded and thanked Pincus for his time. She and Sanger got back in the car and returned to Boston.

The next day, McCormick phoned Pincus to say she would write
a check for $10,000
, with more to come. That night, as Pincus might have been relaxing at home, celebrating with a cocktail, and telling Lizzie that at last he would have enough money to commit real effort to the search for an oral contraceptive, the skies turned a sickish purple as a terrifying tornado tore across Worcester and Shrewsbury. The tornado killed nearly one hundred people, injured more than eight hundred, and left thousands homeless. Entire houses were lifted from their foundations and relocated. Couches and refrigerators were sucked through windows. Sheets of sidewalk flew through the air as if weightless. A brand new tool factory was reduced to a jumble of brick and metal. At the Worcester Foundation, a roof was destroyed on one building and a small amount of lab equipment suffered damage when windows shattered. But no one was hurt.

For Pincus, it was a week to remember.

FIFTEEN

“Weary & Depressed”

K
ATHARINE M
c
CORMICK WAS
always impatient. Once, she complained about Christmas—“the long stretch of holidays irritates me”—
because no work gets done
.

Now, in the fall of 1953, she was even more impatient than usual.

“I haven’t heard a word about the Pincus work,” she complained to Sanger in a letter dated September 28. Only three months had gone by since her meeting with Sanger and Pincus at the Worcester Foundation in Shrewsbury, but already she feared the worst. “I do hope they have not run into difficulties,” she wrote. “There has now been time enough . . . to get some sort of an idea as to how progesterone could function. I am most anxious to hear what they think of it and of
the scope of the tests in action
.”

A week later, Sanger sent word of a troubling rumor: Planned Parenthood did not intend
to fund Pincus’s research beyond January 1954
. Sanger said she had been unable to confirm the rumor, but she was angry and concerned. Pincus’s strongest advocate within the Planned Parenthood administration, Paul Henshaw, had been fired recently after a
power struggle with William Vogt
. Sanger complained to McCormick that the organization’s leaders were paying no attention to “the greatest need of the whole P.P.F. movement . . . that of
a simple, cheap, contraceptive
.” And if all that weren’t enough, Sanger got news that Planned Parenthood had named John Rock—“the ardent Roman Catholic,” as she called him—chairman of its research committee. “You will recall what a very charming person John Rock is,” she wrote, “but that does not mean his interest in contraception is sufficient for him to become a Chairman of a Research Committee, whose object should be the discovery or the
development of a simple contraceptive
.”

Sanger urged McCormick, who had recently moved from California to Boston, to pay Pincus another visit and see what she could learn. “His work, it seems to me,” Sanger wrote, “is the nearest to reality and it would be a shocking and devastating happening . . . if he should not be able to
bring it to a final conclusion
.”

Pincus could see the same issue Sanger did, that Planned Parenthood was not fully committed and might not ever fully commit. As a result, he was hedging his bets.

The scientist had earned his way back into the good graces of
G. D. Searle & Co. In launching his quest for a birth-control pill, he had made it a point to use Searle to supply many of the progestin compounds he was testing, trying one after another to see which worked best in much the same way a chef might try subtly different spices in a new dish. Carl Djerassi at Syntex and Frank Colton, Searle’s scientist, had both discovered how to make synthetic forms of progesterone, but each compound had a slightly different chemical structure and each produced slightly different results. Some worked well by injection but not orally. Some required higher doses than others to be effective. Pincus and Chang worked their way through thousands of laboratory rats in the exploration process, hoping as they worked that the results in humans would track with those in rats. Of the three progestins Pincus liked best—known by their chemical names norethynodrel, norethandrolone, and norethindrone—two were made by Searle. “The Searle Company seems to have
a bit of luck these days
since we have tested a large number of other compounds,” he wrote to Al Raymond, the man who had all but declared Pincus worthless two years prior. Years later, one scientist looking at the data from Pincus’s early tests said he was surprised that Pincus had chosen Searle’s compound because the one made by
Syntex had performed better
. If Pincus were biased toward Searle, he had good reason. He was not confining his activity to progesterone research. He couldn’t be sure the funding Sanger and McCormick provided would continue. Even if the funding did continue, the results were difficult to predict. And even if he got good results with Rock’s patients, he had no idea what would happen when it came time to test the new drug on thousands of women at a time. Was such a thing even possible in a country that still restricted access to birth control? Would foreign countries allow American scientists to come in and experiment on their citizens? The entire project could crash to a halt at any moment.

In the meantime, Searle was funding the Worcester Foundation at a rate of about $5,600 a month, making it the Foundation’s biggest private backer by far and accounting for about
8 percent of the Foundation’s total income
.

Searle executives were interested in Pincus’s progesterone research, but they were interested in his other activities as well. In the summer of 1953, Pincus, clearly optimistic about his standing with the big drug company, and perhaps optimistic as well about his birth-control pill or his baldness cure, purchased nineteen shares of Searle stock at $48.50 per share. He asked the company to deduct the cost of the stock from his pay at a rate of $18.43 a week.