Known as the “Father of the Pill,” chemist and researcher Carl Djerassi, PhD, died on January 30, 2015, at the age of 91 from complications due to bone and liver cancer. Though he is credited with first synthesizing the key component of oral contraceptives, it is an accomplishment that he shared with other scientists, and a title that he never felt fully comfortable embracing. His legacy, both personal and professional, encompasses much more.
“Carl abhorred this [‘Father of the Pill’] term and had always steered away from this designation,” wrote Joseph Chang, PhD, chief scientific officer and executive vice president of product development at Nu Skin (email to M. Blumenthal, March 6, 2015). Formerly, Dr. Chang worked at Pharmanex, now a division of Nu Skin, with Dr. Djerassi. “It’s true he was the third member of a team responsible for the economical synthesis of norethindrone, but Carl was more than a chemist. His talents ranged far and wide and in later years, Carl transitioned seamlessly from a professor of chemistry [and] an art collector to a novelist and playwright. He singlehandedly created a new genre called science-in-fiction.”
Born in Vienna, Austria, Dr. Djerassi and his mother fled to Bulgaria to escape the increasing persecution of the Jews; later, in 1939, he moved to New York City. Showing the initiative and brashness that would come to define his adult life, Dr. Djerassi wrote directly to the first lady, Eleanor Roosevelt, to ask for assistance in funding his education. She responded, and her charity to a struggling refugee helped him earn a degree in chemistry, summa cum laude, from Kenyon College at the age of 18. He earned his PhD from the University of Wisconsin in 1945, the same year he became a naturalized citizen of the United States. After earning his degree, he began working as a research chemist at CIBA Pharmaceutical Co. in New Jersey, where he developed and patented tripelennamine (now sold by Novartis as Pyribenzamine®), the first commercial antihistamine. Four years later, at the age of 26, Dr. Djerassi became the associate director of research at Syntex in Mexico City. It was there that he would take the first steps toward the development of oral contraceptives.
Dr. Djerassi’s work at Syntex first was directed at synthesizing cortisone from diosgenin, a molecule derived from an inedible species of wild Mexican yam (Dioscorea mexicana, Dioscoreaceae). At the time, cortisone was derived mainly from animals, which caused the supply to be expensive and difficult to obtain. While Djerassi was successful in his partial synthesis of cortisone using diosgenin, he made a life-changing discovery: diosgenin could also be synthesized into progesterone, the synthetic version of the female sex hormone. Initially, the discovery was intended to treat infertility, as progesterone injections were already available for that purpose. While scientists were aware that estrogen and progesterone could halt ovulation, using it for contraceptive purposes was impractical and would have involved daily injections for the patient. Again starting with diosgenin, Dr. Djerassi and his team were the first to synthesize norethindrone, a form of progesterone that remained bioavailable during oral delivery. This would become the key ingredient in oral contraceptives, developed and tested by Gregory Pincus, PhD, and Harvard gynecologist John Rock, MD, between 1954 and 1956.
Following the discovery of norethindrone, Dr. Djerassi entered the world of academia, teaching chemistry at Wayne State University in Michigan before moving to Stanford University in California, where he would retire as professor emeritus in 2002. At Stanford, he became notable for his progressive hiring practices and dedication to increasing the diversity of the chemistry field, in particular his willingness to promote and empower women. During his tenure, he continued to hold a variety of positions at Syntex, including serving as president of the company from 1968 to 1972.
In 1968, Dr. Djerassi helped found the Zoecon Corporation and under its auspices continued to pursue his research, this time creating new, environmentally responsible methods of insect control. He maintained an interest in natural products and their chemistry, synthesizing marine natural products and pioneering new methods in organic chemistry.
“He had a long interest in nature as a source or template for drugs,” wrote Janice Thompson, PhD, who worked in Dr. Djerassi’s lab as a research associate (email to M. Blumenthal, February 2, 2015). “Indeed, he and Alex [Alejandro] Zaffaroni, PhD, (early CEO of Syntex) shared this interest and they founded Affymax (1988) to go back to nature looking for drugs with modern methods. Because of my similar interests, I was an early employee of the company, and I managed the natural product chemical collections (among other things),” continued Dr. Thompson. “Our initial focus was on plant extract collections from China, with an emphasis on traditional Chinese medicines [TCMs]. Some years later, he provided the initial funding for what became Pharmanex, and this company was focused on bringing TCMs to market in the United States right after DSHEA [Dietary Supplement Health and Education Act of 1994].”
The multiple commercially successful products Dr. Djerassi produced allowed him to indulge in his favorite hobbies, including art, and he became an avid collector of the Swiss-German painter Paul Klee. After the death of his daughter Pamela, who was a poet and a painter, in 1978, Dr. Djerassi became a patron of many aspiring artists; he sold some of his collection to open the Djerassi Resident Artists Program, an artist colony near Woodside, California, in her memory. Since its inception, more than 2,000 artists have participated in the program.
Following his own artistic desires, Dr. Djerassi began publishing his own short stories and fiction in 1986. His novels created a genre he termed “science-in-fiction.” Combining his scientific background and literary flair, he sought to integrate two fields of study that were perceived by some to be incompatible — art and science — and examine the human side of scientists and their work. In 1997, he continued in this vein as a playwright. His seven plays have been performed around the world, and all of his works have been translated into several different languages. He also published his memoir, This Man’s Pill (Oxford University Press, 2001), to commemorate the 50th anniversary of his discovery in Mexico.
Dr. Djerassi’s work gained him international acclaim and a staggering number of awards. For his work on the synthesis of a steroid contraceptive, he received the National Medal of Science in 1973, the first Wolf Prize in Chemistry in 1978, and was inducted into the National Inventors Hall of Fame in the same year. He received 32 honorary doctorates from institutions around the world, and his native Austria honored his work by issuing a stamp with his likeness in 2005.
Carl Djerassi — a self-described “intellectual bigamist” and “intellectual smuggler” — died at his home in San Francisco, California. He is survived by his son, Dale; stepdaughter, Leah Middlebrook; and a grandson.
—Hannah Bauman