Carl Djerassi (1923–2015)

Few lives at the top of chemistry and industrial accomplishments in the 20th century have been as remarkable as that of Carl Djerassi, who died in San Francisco on January 30 at the age of 91. To a considerable extent, his life became known as ‘fascinating’, catalyzed by his own portrayal of it. This feature of his persona cannot, and will not, dilute the one major scientific contribution he made, but it somewhat obfuscated the true picture.Photo: Margo Davis.View Large Image | View Hi-Res Image | Download PowerPoint SlideDjerassi was born in 1923 in Vienna to secular Jewish parents who were physicians. After a brief move to Bulgaria, his father’s birthplace, Djerassi and his mother returned to Vienna for its cultural richness, including the superior schooling available. After the annexation of Austria by Nazi Germany, his mother and he were among the quota for evacuation to America. Now 16, Djerassi promptly displayed an example of the bravado that would typify his career and life — he sought the intercession of none other than Eleanor Roosevelt for college financial assistance, successfully. After a short stint at Tarkio College in Missouri, where he earned a bit of additional money by giving lectures on Bulgaria and Europe to church groups, he obtained a degree in chemistry from Kenyon College in Ohio, followed by a job at the American branch of the Swiss pharmaceutical company Ciba in Summit, New Jersey. Here, he was part of a group that developed pyribenzamine, a major antihistamine. He stayed at Ciba only a year and then pursued and obtained a Ph.D. from the University of Wisconsin in 1945, followed by a return to Ciba for the next three years.By the late 1940s, word of Djerassi’s talent had spread, notably at the annual Laurentian Hormone Conferences in Quebec, where one of several with open ears was the steroid chemist George Rosenkranz. He had been appointed in 1945 to lead a newly formed company, Syntex, whose goal was to pursue the production of steroids from plant sources, the most timely of such quarries being cortisone. Djerassi joined this intrepid outfit in 1949 and its fortunes soon rose.Beyond cortisone, Syntex and its precursor company had been interested in progesterone, the steroid hormone that maintains the condition of pregnancy. It had long been suspected that administration of exogenous progesterone might produce a contraceptive state. Although available or readily converted from plant sources — chemical achievements by Syntex’s co-founder Russell Marker — progesterone itself had limitations for an oral delivery-based pharmaceutical. In 1951, Djerassi and Luis Miramontes, a student doing his Ph.D. at the company, synthesized multigrams of the progesterone derivative 19-norprogesterone, with the means of evicting the methyl group at position 19 perhaps having been conveyed to Djerassi by his former Ph.D. adviser A.L. Wilds. They then attached an ethynyl group at position 17, which was correctly anticipated to boost the compound’s oral efficacy. A historical point often overlooked is that Syntex’s initial interest in orally-active progesterone analogs was based on their envisioned use in the treatment of certain gynecological and menstrual conditions, not to induce a contraceptive state. But the latter potential soon became evident and this shifted Syntex’s fortunes into high gear, particularly since the quest for the production of cortisone had been won by Merck in 1949.The Djerassi team’s process for 19-nor-17α-ethynyltestosterone (norethindrone), and the patent that protected it, launched Syntex into the oral contraceptive market. This project, led by Djerassi, is the basis for his correct claim that they were the first to synthesize the steroid that became, later, the basis for one of the first two oral contraceptives (the Syntex pill being second to one brought to market by G.D. Searle). Some objected to Djerassi’s self-portrayal as ‘the father’ of the Pill. He, however, was always careful to state that his achievement was being the first to synthesize a compound that would become one of the oral contraceptives. In addition, he gracefully conceded in his several autobiographies that a more correct term was ‘a’ father, giving proper credit to Gregory Pincus and M.C. Chang at the Worcester Foundation and characterizing both Pincus and himself as ‘fathers’.Djerassi, like most industrial chemists, held no invention rights of his own but bought shares in the company. In due course, he became both wealthy and world famous. He used these two stations vivaciously all through the remainder of his life.By the time of Syntex’s zenith, Djerassi had become a Professor at Stanford University where he displayed an astonishing level of research productivity. He also was a prolific classroom teacher, welcoming a heavy load, not only in chemistry but also in an inspired human biology course he created that was wildly popular (students had to apply with an essay and only half got in). He trained more than 300 graduate students in his overall career and, within the guild, became internationally recognized for his work on the application of spectroscopic methods to organic chemistry, in parallel with the wider fame he acquired in the Syntex era.With time, Djerassi increasingly became a public statesman of science, particularly around the Pill and the social revolution it had created. He bought a vast tract of land overlooking the Pacific, naming it ‘SMIP’ (for ‘Syntex Made it Possible’), where he hosted artists and other intellectuals and assembled a fine collection of paintings, especially by Paul Klee. In these years, he also embarked on an admirable philanthropic strand in his life, which he continued. But his greatest passion during this phase of his life and afterwards was writing fiction and then plays — the promotion of which he undertook with fierce intensity. Most of these centered on science and/or the flaws of its practitioners, often coupled with broader societal themes. He staged his plays in Vienna, London and New York and elsewhere, and had hoped to have reviews like Michael Frayn got for ‘Copenhagen’, for example, but these did not come. He also wrote four autobiographical works and in the final one, published only months before his death, Djerassi delved into his motives behind these endeavors in fiction and on the stage. One can admire him for the cleverness of his novels and plays, as well as a well-intended desire to convey science and its culture, but there was often a certain ponderous tone to the dialogue. Djerassi wanted his plays to not only be applauded by critics for their virtues as pure theater, but to have them be seen as exemplars of his statesmanship for the cause of science, analogous to the contributions of J.B.S. Haldane as an essayist or Carl Sagan as a populist. He may have fallen short on both of these laudable goals, but his endeavors deserve admiration.Any chemist of Djerassi’s accomplishment would hope for esteem in the guild, and this he surely had, as well as a wider circle beyond chemistry, including sociology. He received many honors including both the U.S. National Medal of Science and National Medal of Technology, and the first Wolf Medal of Israel. As one who always referred to himself, correctly, as a displaced person, these surely were significant. In the last decades of his life, Djerassi’s unquenchable intensity was manifest by a very active triangulation between Vienna, London and San Francisco, even as his final illness began to close in. Indeed, after his death his calendar was found to have entries of numerous lectures and trips scheduled way into 2015. He was predeceased by three wives and a daughter, and is survived by a son, grandson and stepdaughter.Carl Djerassi gave very much to the world. He was as complex as he candidly portrayed himself, and leaves us saddened that we will no longer have the man and his works to surprise and stimulate us.