Obituaries

Carl Djerassi

BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h1727 (Published 30 March 2015) Cite this as: BMJ 2015;350:h1727
  1. Ned Stafford, Hamburg

Key figure in the development of oral contraceptives

Joerg Sarbach/AP/Press Association Images

As a child in the 1930s, Carl Djerassi had planned to study medicine in his native Vienna, as both his mother and father had done. But in 1938 Nazi Germany annexed Austria. His parents were Jewish, and Djerassi and his mother fled, eventually settling in the USA. Mainly because of tight family finances, Djerassi would not study medicine. But as a chemist he would have a key role in one of the most important medical achievements of the 20th century—the development of oral contraceptives, known around the world simply as the pill.

In 2007 a panel of The BMJ’s editors and advisers named the pill as one of the top 15 medical milestones since 1840,1 the year when The BMJ was first published. Writing in The BMJ at the time, Djerassi agreed with this assessment. He noted that the two words—the pill—needed no additional explanation and were understood by almost everybody to mean oral contraceptives.2

“What single procedure or vaccine would be known by the equivalent labels of ‘the operation’ or ‘the jab’?” he wrote. “The answer is, none.” He added that “no other milestone has had as many societal, ‘non-medical’ consequences; the pill is a stone thrown into water that has produced ripples and waves way beyond any reasonable expectation.”

The first step toward the development of the pill’s key ingredient began in 1949, when the 26 year old Djerassi accepted a position as associate director of research in a small laboratory in Mexico City, operated by pharmaceutical firm Syntex. Djerassi had already attracted attention as a “wunderkind” chemist when he helped develop tripelennamine, the first commercial antihistamine,3at the pharmaceutical company Ciba in New Jersey. At Ciba he had also developed a deep appreciation of the powerful connection between chemistry and human health.

In Mexico, Djerassi initially focused on developing a simpler synthesis of an anti-inflammatory cortisone from the steroid diosgenin, which was derived from Mexican wild yams. After successfully completing this task in mid-1951, Djerassi focused on producing a synthetic version of progesterone—called a progestin—that could be ingested orally. At the time, progesterone was being used to treat menstrual disorders and infertility, but it had to be injected intravenously.

Djerassi’s team consisted of George Rosenkranz, director of the Syntex laboratory, and Luis E Miramontes, a Mexican student. On 15 October 1951 the team successfully synthesised norethisterone (sometimes called norethindrone), which could mimic progesterone when taken orally. The next month a US patent application was filed, with all three members of the team listed as inventors.

Although the team had developed norethisterone as a potential oral treatment for menstrual disorders and infertility, earlier studies by others had shown that high doses of androgens, oestrogens, or progesterone could halt ovulation. By the mid-1950s medical researchers—including Gregory G Pincus, John Rock, and M C Chang—were actively investigating the use of norethisterone, and two other progestins were subsequently developed by pharmaceutical firm G D Searle as oral contraceptives.

In 1957 the US Food and Drug Administration (FDA) approved the progestins as treatments for “menstrual disorders.” In 1960 the FDA approved Searle’s Enovid (mestranol and norethynodrel) for use as an oral contraceptive, and two years later it approved Syntex’s Ortho-Novum (norethindrone and ethinyl oestradiol). In subsequent years, other pharmaceutical firms entered the oral contraceptive market.

Because of his employment agreement with Syntex, Djerassi received only a token payment of $1 as an inventor of norethisterone. He was, however, able to buy stock shares of the private company at the bargain price of $2 each. When Syntex became a publicly traded company, Djerassi became a wealthy man. He later bought a large ranch near San Francisco and named it SMIP, short for Syntex Made It Possible.

Djerassi was born on 29 October 1923 in Vienna. His Bulgarian father was a dermatologist and specialist in sexually transmitted diseases. His Austrian mother initially practised medicine and later dentistry. His parents divorced when he was a young child, and Djerassi spent summers with his father in Bulgaria. When he and his mother fled Austria in December 1938, he went to Bulgaria while his mother travelled to England to arrange passage to the US.

In December 1939 Djerassi and his mother arrived in New York City with around $20 cash. They settled in nearby New Jersey, and Djerassi enrolled at Newark Junior College, which only offered a two year programme. He wrote a personal letter to Eleanor Roosevelt, wife of President Franklin D Roosevelt, saying he needed financial help. Djerassi received a scholarship to attend Tarkio College in Missouri. After one year he transferred in 1941 to Kenyon College in Ohio, where, a year later and only 18 years old, he earned a bachelor’s degree in chemistry.

After spending a year at Ciba as a junior research chemist and also marrying the first of his three wives, he began doctoral work in organic chemistry at the University of Wisconsin at Madison, earning a doctorate in 1945. He returned to Ciba, staying until his move to Mexico. His marriage ended in divorce in 1950 after Norma Lundholm, a woman he had been having an affair with, became pregnant. Djerassi later said a condom had failed. He married Lundholm, and they had a daughter and a son.

In 1952 he left Mexico to take an associate professor position at Wayne State University in Detroit, where he initiated natural product research of antibiotics, alkaloids, and terpenoids. He returned to Mexico City in 1957 as vice president of research at Syntex, and in 1959 he was appointed professor of chemistry at Stanford University.

Widely recognised as a brilliant and ambitious workaholic, Djerassi introduced new physical research techniques for organic chemistry and life sciences. The techniques, including mass spectrometry and optical rotatory dispersion, enhanced research strategies, especially for steroid hormones and alkaloids. He held several high level positions with Syntex into the 1970s, and was affiliated with several start-up firms. These included Zoecon, which he founded in 1968 to produce insect pest control products using contraceptive principles.

Djerassi published more than 1200 scientific papers, and in his Stanford laboratory he trained some 300 chemists from more than 50 countries. He was also a public advocate of the use of oral contraceptives and spoke out on other social issues. He was added to President Richard Nixon’s so called enemies list for his opposition to US involvement in the Vietnam war.

In 1976 he and his second wife divorced. Two years later their daughter committed suicide on Djerassi’s ranch. In her memory, he turned part of the ranch into an artists’ colony. In the mid-1980s, after nearly 40 years dedicated to research, Djerassi decided to close his Stanford laboratory gradually and focus on creative writing instead. One of the two major impulses for the decision came from his 1985 marriage to Stanford English professor, Diane Middlebrook, who was a feminist, poet, and an acclaimed biographer. Her books include Her Husband: Ted Hughes and Sylvia Plath—A Marriage. The other impulse came from his being diagnosed with colon cancer.

In 1989 he published his first novel, Cantor’s Dilemma, about a cell biologist who must decide whether or not to commit scientific fraud to win a Nobel prize. Other novels about scientists followed, a genre he labelled “science in fiction.” He also wrote three autobiographies and several plays, including Foreplay: Hannah Arendt, the Two Adornos, and Walter Benjamin, which played in London in 2014.4

During the last two decades of his life, Djerassi divided his time between his California ranch, London, and Vienna.

Predeceased by his wife, Diane Middlebrook, in 2007, Djerassi leaves a son and a stepdaughter.

Notes

Cite this as: BMJ 2015;350:h1727

Footnotes

  • Carl Djerassi (b 1923; bachelors degree in chemistry from Kenyon College, Ohio, 1942; doctorate in chemistry from the University of Wisconsin, Madison, 1945), died from complications of liver and bone cancer on 30 January 2015.

References

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