But Russell Marker turned the entire problem upside-down. Instead of viewing progesterone synthesis as a game of addition, he saw it as a game of subtraction. Rather than building the steroid out of smaller molecules, he decided to start out with an even larger molecule and whack off pieces until only progesterone was left. (In the jargon of chemistry, he intended to perform a degradation rather than a synthesis.) All he needed was a starting molecule that was even larger than progesterone.
Marker finally settled on a class of compounds known as phytosterols, large molecules similar to cholesterol but that are found in plants instead of animals. Marker attempted to prune away pieces of the phytosterol molecule in order to leave behind a progesterone molecule. He achieved success almost immediately by starting with a molecule of diosgenin—a type of phytosterol found in sarsaparilla roots—and degrading it into progesterone. It was a very good start, but even though he had demonstrated that his novel method worked, he still needed to show that his degradation technique could create progesterone on an industrial scale. To do that, he would need lots and lots of diosgenin. And that presented a new problem.
The stringy roots of the sarsaparilla plant were simply too meager a source of diosgenin to be useful in commercial production. Marker needed to find another plant with diosgenin—one that was large, cheap, and packed full of diosgenin molecules. He knew there were several species of plants containing diosgenin in the southwest United States, all tuberous plants with thick roots. So—like Valerius Cordus four centuries earlier—Marker embarked upon a plant-hunting expedition. In 1940, he ventured into the hot, unruly wildlands of Texas and Arizona. He tried root after root, but none of the thin American tubers produced enough diosgenin.
He eventually drifted south, crossing the Rio Grande into Mexico. There, in the state of Veracruz, Marker finally unearthed a plant with a remarkably high concentration of diosgenin. It was Dioscorea composita, the Mexican yam. These yellowish tubers boasted elephantine roots that weighed up to one hundred pounds, requiring a wheelbarrow to move them around. Marker hauled one fifty-pound yam back into the United States, bribing custom officials to allow him to transport the prohibited agricultural material across the border. Back at Penn State, he applied his degradation process to the diosgenin extracted from the yam. Success! The D. composita produced enough progesterone to enable industrial-level production.
Marker approached pharmaceutical companies and touted his clever degradation method, hoping to partner with one of them to produce commercial progesterone. These meetings did not go well. Marker was far more skilled as a chemist than as a pitchman, often lapsing into dull and highly technical disquisitions. But perhaps more damaging to Marker’s cause, pharma execs were already skeptical about his unheard-of technique for creating the progesterone—and when they learned that this degradation process required gargantuan yams from a third-world country just a couple decades removed from a revolutionary war, they merely shook their heads in disbelief.
D. composita could grow only in the warm, dry climate of Mexico, which at the time was a disorganized and highly undeveloped country harboring dangerous anti-American sentiment against its wealthy and arrogant neighbor to the north. The pharmaceutical companies were convinced there was no way the yam could be reliably and safely collected in Mexico on the scale necessary for industrial production. Every pharma company that Marker approached turned him down.
Marker reacted to this setback in his usual manner. He resigned from his highly productive academic laboratory at Penn State and set up his own private lab in an old pottery shed in Mexico City. If the pharma companies would not collaborate with him, he would manufacture progesterone on his own. He paid Mexican laborers to unearth ten tons of yams, enough to fill a large truck, and began degrading their diosgenin. Working in isolation for two months, Marker produced an incredible three kilograms of progesterone—an amount that was quite probably more than the total supply of synthetic progesterone on Earth. Since progesterone was selling for $80 per gram—approximately $1,000 per gram in 2016 dollars—Marker had created the equivalent of three million dollars’ worth of the hormone in his very first try. He had discovered a synthetic chemistry philosopher’s stone: a means to transform yams into gold.
But he still needed a pharmaceutical business partner to help him distribute the hormone. He no longer wanted anything to do with the American pharma businesses that had turned up their noses at him. On the other hand, he knew nothing at all about the Mexican pharmaceutical industry and he only spoke a few rudimentary words of Spanish. Undaunted, he leafed through the Mexico City phone book until his finger came to rest upon a promising listing, a small pharmaceutical enterprise by the name of Laboratorios Hormona S. A.
The owners of Laboratorios Hormona were German and Hungarian Jews who had fled the rising anti-Semitism that consumed 1930s Europe. They joined forces with Marker and together founded a new company that they anointed Syntex S. A. The firm was devoted to manufacturing hormones using Marker’s degradation process. But just as Marker’s former bosses at Penn State, the Rockefeller Institute, and the Ethyl Corporation might have predicted, less than two years after Marker founded Syntex he sold all his shares in the company and left Mexico, abandoning all rights to Syntex’s unprecedented supply of progesterone. He also abandoned science. He severed all ties with former friends and colleagues in chemistry and dropped out of sight in order to devote himself to a new passion: eighteenth-century silversmithing. This time, the interest stuck. Until the end of his days, Russell Marker spent most of his time fashioning intricate Rococo tureens and surtout des tables.
Like Vonnegut’s fictional Hoenikker, Marker was never concerned with money or the practical utility of his research. He just liked to play with the “real games” of nature. Despite his eccentric and impractical nature, he had left behind what no other scientist had achieved: a breakthrough method for creating progesterone on an industrial scale.
Witnessing the out-of-nowhere success of Syntex, several American companies finally adopted the Marker degradation method, and by the early 1950s there were more than two hundred different progesterone compounds on the market. This abrupt glut of the hormone led to a flood of new research on female reproduction at academic laboratories around the world. One of these laboratories was in Cambridge, Massachusetts, and run by a Jewish biologist named Gregory Pincus.
In the early nineteenth century, a large influx of wealthy and educated German Jews immigrated to the United States and were quickly assimilated into American culture, becoming New York bankers, slave-owning plantation owners, western bordello madams, and Indian-fighting cavalrymen. The next wave of Jewish immigrants followed a very different path, however. Arriving at the end of the nineteenth century, these less well-to-do Eastern European Jews looked and sounded quite different from most Americans and mostly headed to inner city ghettoes like Manhattan’s Lower East Side.
The old line Jews, already integrated into mainstream America, grew concerned about the new arrivals. Many of the established German Jews took it upon themselves to try to help Americanize their Eastern European brethren, and one of the most prominent examples of these charitable efforts was the Baron de Hirsch Fund. The Jewish philanthropist Maurice de Hirsch admired the way Norwegian immigrants in Minnesota had rapidly become good American wheat farmers. The perceived success of these Scandinavian émigrés inspired de Hirsch to put forth a straightforward idea. Instead of placing the incoming Eastern European Jews in ghettoes, what better way to convert them into full-blooded Americans than to turn them into farmers. Just as Norwegian immigrants became wheat farmers in Minnesota, de Hirsch’s Fund would help Jewish immigrants become chicken farmers in New Jersey.
In 1891, the town of Woodbine, New Jersey was founded as an agricultural settlement for Eastern European Jews with the aid of de Hirsch money. The fund subsidized the purchase of farm land for Jewish immigrants and paid to train them for their new lives. However, de Hirsch’s grand dream did not work out quite t
he way he envisioned. Most nineteenth-century European immigrants to the United States, including the Norwegians, had already been farmers in Europe. When they came to the New World, they brought with them extensive knowledge of farming. European Jews, in contrast, were mostly merchants and tradesmen. Instead of possessing farming skills, most of the Eastern European Jews arrived in the USA brought with them a long tradition of scholarly religious study, frequently analyzing religious texts for rabbinical guidance on everyday matters.
In Woodbine, the imported Jews applied their Talmudic skills to chicken farming. They contemplated the fowl and inquired, “Vi tut a hun lebn?” How does a chicken live? The Eastern European immigrants scrutinized the bird carefully, trying to unriddle how it produced eggs and how one might improve upon its egg-laying abilities. Since these Jews were used to setting up yeshivas (educational institutions) to study religious texts, it was quite natural for the Woodbine community to establish the Baron de Hirsch Agricultural College in 1894 to formalize their inquiry into the mysteries of the chicken. If these Jews were going to be farmers, they were going to be scholarly farmers.
Gregory Pincus was born in Woodbine in 1903, a member of the first generation of Woodbine-raised Jews. Two of his uncles were agricultural scientists at the Baron de Hirsch College, exposing him at an early age to the idea that it was possible to manipulate and improve upon the biology of Mother Nature. Studious and hard-working, Pincus received a Ph.D. in biology from Harvard University, became an assistant professor in general physiology at Harvard, and then a professor of experimental biology at Clark University in Worcester, Massachusetts, where he founded the Worcester Foundation for Experimental Biology. In this academic laboratory, Pincus used progesterone to investigate what he called “the big questions”: “Why does an egg start to develop and why does it continue to develop?”
Though Pincus seemed to have fulfilled de Hirsch’s dream of integrating Eastern European Jews into the American way of life, Pincus remained an academic outsider. The period between the 1910s and the 1940s was the era of numerus clausus, a bigoted university quota system that restricted the number of Jews permitted at Ivy League institutions. Pincus looked different and spoke differently than his mostly WASPy colleagues. His foreign appearance would eventually contribute to a scandal that changed the course of his career.
At Clark, Pincus studied the eggs of the Oryctolagus cuniculus, a fluffy-tailed, buck-toothed laboratory rabbit. However, he soon found that it was difficult to precisely control the intricacies of rabbit fertilization. He began to wonder—instead of fertilizing the rabbit egg inside the rabbit—in vivo, in the vocabulary of biology—might it be possible to fertilize the egg outside of the rabbit? After several years of experimentation, he managed to fertilize a rabbit egg in a Petri dish. This was the very first in vitro fertilization of a mammalian egg.
Though Pincus did not seek any publicity for this achievement, the newspapers soon characterized Pincus as a modern day Frankenstein who was engineering “fatherless rabbits.” Lending credibility to such charges was Pincus’s personal appearance: his disheveled hair, crooked eyebrows, and dark and wild eyes made Pincus the spitting image of Rotwang, the deranged scientist who built a female robot in the contemporaneous film Metropolis. His notoriety soared when a reporter asked him if he intended to grow human beings inside of test tubes. Even though he actually replied, “I am not trying to create human life in the laboratory,” the newspaper misprinted the quote as “I am trying to create human life in the laboratory.”
For the rest of his career, Pincus was dogged by questions about his blasphemous (and nonexistent) process of “Pincogenesis.” The fact that he was foreign-looking and Jewish only exacerbated the cloud of condemnation that hung over him. Though Pincus did his best to remain out of the public spotlight, the damage had already been done, and he found it difficult to raise funds for his research. He even took up an extra shift as a lab janitor to help keep his laboratory afloat. Discredited and isolated, Pincus was not sure how he would find enough financial support to enable his laboratory to resume its former luster investigating the big questions. Things looked fairly hopeless until he met Margaret Sanger.
Sanger was born in New York to a working-class Irish Catholic family—which in 1879 meant a very large family. Sanger believed that her mother, who had borne eleven children and endured seven miscarriages, perished at age fifty as a result of the debilitating effects of so many pregnancies. Staring across her mother’s coffin, Sanger pointed her finger at her father and cried, “You are responsible for this! She had too many children!”
Sanger’s hostility towards uncontrolled pregnancy was reinforced by her work as a nurse on the Lower East Side of Manhattan. One common feature in the lives of the poor immigrants to whom Sanger tended was the botched five-dollar back-alley abortion, pursued by desperate women who could not support another child. Sanger yearned for a cheap, convenient, and reliable method of birth control to help these women, but no new method had been developed since the invention of the diaphragm in 1842 for women and the full length condom in 1869 for men. In 1914, Sanger coined the term “birth control” and began to provide women with pamphlets and diaphragms—activities that violated federal law.
The anti-obscenity Comstock Act of 1873 made it illegal in the United States to disseminate information on contraception. In addition, thirty states had laws explicitly prohibiting the distribution of contraceptives. Consequently, during World War I, American servicemen were the only Allied troops not provided with condoms and, not surprisingly, American soldiers were afflicted with the highest incidence of sexually transmitted disease of all the warring countries.
Under the Comstock Act, Sanger was indicted in 1915 for sending diaphragms through the mail. She was arrested again in 1916 for opening the first birth control clinic in the country, in New York. But Sanger would not be thwarted. In 1921 she founded the American Birth Control League, the precursor to Planned Parenthood. For the following three decades she did everything in her power to raise awareness of birth control and to deliver contraceptives to American women. All the while she was obsessed with a singular dream. She envisioned a pill for women that could be taken like Aspirin that would enable them to take control of their pregnancies.
Sanger was no scientist. She did not know anything about the hormonal biology of reproduction, the science of pharmaceutical development, or even how the drug industry worked. She had no clue how feasible—or how wildly implausible—an aspirin-like birth control pill actually was. Though she repeatedly approached pharmaceutical companies with the idea of developing an oral contraceptive, they always rebuffed her, citing the Comstock Act and the fear of a Catholic boycott of all their products. “Besides,” one pharma exec knowingly informed her, “Why would women want to take a pill every single day just to control conception?”
Despite her passion for a birth control pill, as 1951 rolled around, Sanger, now in her seventies, had all but given up. She had visited every major pharma company, some more than once, and had failed to persuade a single one of the potential value of such a drug; and she still had no idea about whether it was even scientifically possible to create the hypothetical pill. Sensing she was running out of time, she decided to switch tactics. Perhaps she could persuade a scientist to try to create a pill entirely on his own, outside of the pharma industry.
If she had possessed any knowledge of the realities of drug development in the 1950s, she would have realized just how unlikely it was for an academic scientist to create a novel medication at a university; post-FDA, the development costs for new drugs were prohibitive even for the best-funded academic laboratories. Oblivious to the extreme impracticality of her idea, she began to contemplate which scientist to target. He would have to be someone with a proven record of quality scientific research in female reproductive physiology. He would also have to be someone in a position so desperate they would be open to the overtures of a seventy-year-old feminist activist pursuing her wild dream o
f helping women control their fertility—and willing to pursue a controversial and probably illegal drug. Sanger eventually identified someone who checked off all the boxes. It was Gregory Pincus.
Though she had no ability to evaluate Pincus’s scientific prowess, the same achievement that had publicly disgraced him and rendered him desperate—in vitro fertilization—persuaded her that he possessed the talent to create a birth control pill. Sanger invited Pincus to a dinner party hosted by the director of the Planned Parenthood Federation. By the end of the dinner, she had secured him a Planned Parenthood grant to support his existing research into animal fertilization. But she also outlined her real goal, the development of the world’s first oral contraceptive. He confidently assured her that, yes, he could indeed develop such a drug—all he needed was a great sum of money.
Though the American businessman King C. Gillette is often considered the inventor of the disposable safety razor, it is more accurate to say that Gillette had the inspiration to create a disposable safety razor. He convinced a metallurgist named William Emery Nickerson to actually figure out how to turn Gillette’s inspiration into a commercial reality. At the time, it was not known how to sharpen a thin square of steel to a razor-sharp edge, but with Gillette’s financial support Nickerson managed to solve this tricky engineering problem. Margaret Sanger and Gregory Pincus formed a similar relationship. Sanger nursed a dream of an oral contraceptive, but had no idea how to convert her dream into reality. So she found someone who did. And just as Gillette funded Nickerson’s research, Sanger found a way to fund Pincus. That way was Sanger’s good friend Katharine Dexter McCormick.
McCormick’s life started out like a storybook. She was born into an aristocratic Chicago family whose roots could be traced all the way back to the Mayflower. She studied biology in college and became the first woman to graduate from MIT. She married the dashing young Stanley McCormick, the heir to the massive International Harvester Company fortune. But before long, her charmed life crumbled around her. Her husband developed schizophrenia in his early twenties and was soon lost to incurable madness.
The Drug Hunters Page 17