Russell Marker. Image: Penn State University Archives
Welcome to the second installment of our series chronicling the history of the birth control pill. Previously, we learned about the role a sex hormone called progesterone plays in inhibiting ovulation. Scientists had no easy way to isolate significant amounts of this chemical and wanted to find a quick and inexpensive method for synthesizing large quantities of progesterone.
Russell Marker was born to Maryland sharecroppers in 1903. Hoping to escape rural life, Marker was one of only two students in his junior-high class to attend high school. He graduated in three years and enrolled at the University of Maryland, where he earned bachelor’s and master’s degrees in chemistry. He needed one more class to receive his doctorate, but refused to take it, believing he had already mastered his chosen subject, organic chemistry. He was only interested in working in the lab and thought the required course would be a waste of his time. (The university did eventually award him an honorary doctorate in 1987.)
A wild-growing yam in Mexico provided chemicals that could be refined into progesterone, the active ingredient in the Pill.
At the time, the scientific community was abuzz with discoveries being made about hormones. They held tremendous potential for research, but scientists couldn’t figure out how to isolate large quantities of them for study. Up for a challenge, Marker set out to find a way to synthesize one hormone, called progesterone, in abundance. He hypothesized that plants from the genus Dioscorea, which includes yams and agaves, would be cheap sources of steroid hormones. Marker was specifically hoping to find plants rich in sapogenins, which are chemically similar to cholesterol.
The structures of cholesterol and progesterone are similar; our bodies can convert cholesterol to progesterone. Image: Open University
Our bodies can alter the chemical structure of cholesterol and convert it into sex hormones such as progesterone, but the process could not be replicated in the lab. Marker, however, believed that he could convert cholesterol to progesterone by manipulating pH and temperature levels. He and his assistant conducted scores of experiments, each process tedious and slow. Eventually, though, they produced something that was one step away from human pregnanediol, which itself was easily converted to progesterone. They had done this by bringing sapogenin (derived from sarsaparilla) to 200 degrees Fahrenheit overnight in a sealed tube of acetic anhydride. This technique, still in use today, became known as the Marker degradation.
Having found a successful technique for converting plant-derived sapogenin to progesterone, Marker sought a plant that could produce progesterone in greater abundance. In the early ’40s, while visiting a botanist in Texas, Marker looked through his host’s library and found a photograph taken in Veracruz, Mexico, of a large tuber, cabeza de negro, which could supposedly reach several hundred pounds. Despite political unrest and an inability to speak Spanish, Marker traveled to rural Mexico and enlisted local help in locating cabeza de negro, which he learned was slow-growing and would thus be impractical to cultivate agriculturally — but the wild supply seemed to be without limit. Back in the United States, he was able to extract sapogenin from a dried portion of the root, and converted it into progesterone.
In October 1942, Marker, with half of his life’s savings, returned to Mexico on his own, where locals helped him collect 10 tons of the root. It was chopped with machetes into chips, sun-dried, and taken to Mexico City to be ground into a powder. He extracted the dried root with alcohol and evaporated it until it became a syrup. He returned to the United States with this syrup, and produced more than three kilograms of progesterone — the biggest batch of progesterone that had ever been in one place. In January 1944, having relocated to Mexico City, he co-founded a lab named Syntex — a portmanteau of “synthesis” and “Mexico” — to synthesize progesterone on a large scale.
Dioscorea composita is a wild yam, different from those we eat. In its natural state, the yam won’t prevent pregnancy, but it contains a chemical that can be transformed in a laboratory into the active ingredient in hormonal birth control. Image: Science Museum, London
In May 1945 he left Syntex over financial disputes and founded a competing lab in Texcoco, 30 miles from Mexico City, called Botanica-Mex. However, he was having trouble obtaining cabeza de negro as his root collectors were mysteriously dying or being attacked — these crimes were believed to be perpetrated by Syntex, eager to retain their monopoly. Marker started to collect other varieties of wild yams in Mexico, including one that contained a nearly pure sapogenin (a subtype called diosgenin). This particular wild yam was called barbasco by the indigenous population, and it became the industry’s choice for the raw material in hormone synthesis. While cabeza de negro took six to nine years before it contained enough diosgenin to be commercially viable, barbasco matured in half that time.
Barbasco proved an even greater boon when chemists at Upjohn discovered how to use an enzyme to attach an additional oxygen atom to the molecule, enabling them to produce cortisone and all of its derivatives from diosgenin. Thus, barbasco not only yielded progesterone for birth control pills, but could be synthesized into cortisone, another chemical that revolutionized medicine. Mexico’s hormone industry was further strengthened by the inability to grow barbasco outside of its native range — it was never successfully transplanted in the United States, and even when it could be grown in other places, the diosgenin content was significantly lower when compared with those growing wild in Mexico.
Now that we had a way to produce progesterone in abundance, we were one step closer to being able to create the “magic pill” that Margaret Sanger dreamed of.
Stay tuned for our next installment of this series, in which we will meet the scientists who figured out how to make progesterone into a pill.
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