Reflections

This section collects the essays from Reflections from the Frontiers (Explorations for the Future: Gordon Research Conferences 1931-2006), GRC's 75th anniversary commemorative publication.

Reflections on Matter
Carl Djerassi
Carl Djerassi
Stanford University
Competition, Steroids, and Maple Syrup

In 1951, as a twenty-eight-year-old scientist, I attended the first Steroid Chemistry Gordon Research Conference. At the meeting I found myself among top-notch chemists responsible for the rapid advances of steroid chemistry over the past half-decade, in a setting much like the Olympic arena where world-class athletes perform, compete, and demonstrate their brawn.

My own path to the height of the organic chemistry field had been steep and fast. As the offspring of two European physicians, my interest in medicine from a young age was not surprising; however, as a teenage refugee in the United States, I was financially unable to attend medical school. Learning of the many pharmaceutical companies in New Jersey, I sent employment inquiries to every address I could find. The only response came from the American branch of the Swiss company CIBA. Starting work there in 1942, immediately after graduation from Kenyon College, was my first foray into the world of medicinal chemistry.

As a junior chemist I was assigned to the lab of Charles Huttrer, where success came at an unusually fast pace. In less than a year we developed one of the world’s first antihistamines–Pyribenzamine, or tripelennamine. My interest in steroids was inspired by older laboratory colleagues at CIBA and by Louis Fieser’s treatise Natural Products Related to Phenanthrene. Recognizing the difficulty of earning a Ph.D. while working full-time, I left CIBA in 1943 to attend graduate school at the University of Wisconsin at Madison. I arrived just in time to witness Alfred Wilds’s and William Johnson’s groundbreaking work on the total synthesis of steroids. (Only one steroid, equilenin, had been totally synthesized at the time.) I was inspired by Wilds and set the sights of my doctoral thesis on the transformation of testosterone into estradiol.

Racing through my graduate studies, I received my Ph.D. in 1945 and returned to CIBA to continue work on antihistamines and antispasmodics. I used the independent research time CIBA granted to its chemists for steroid research just as the field’s breakthroughs were erupting. By 1949 Philip Hench and his colleagues at the Mayo Clinic had discovered the antiarthritic properties of cortisone. Millions of unrelieved arthritis sufferers seemingly guaranteed a huge market, but the partial synthesis of cortisone from bile acids (achieved by Lewis H. Sarett at Merck) had so far proven time consuming, complex, and expensive. Later that year I accepted an offer from George Rosenkranz to join the tiny company Syntex in Mexico City as associate director of chemical research. Our goal was to develop a superior synthesis of cortisone from a plant raw material (diosgenin from Mexican yams).

Though our methods were different, the Syntex team was engaged in close competition with two groups at Harvard University–one run by Robert Burns Woodward and one by Louis Fieser–and a group at Merck under Max Tishler. In June 1951 our three-man team sent a communication to the editor of the Journal of the American Chemical Society (JACS) titled “Synthesis of Cortisone.” We later learned that the journal (edited at Harvard) had agreed to hold up publication for a few days until Woodward and Fieser had submitted their communications. The Merck group’s submission was accepted shortly after. Competition was fierce; nonetheless, four communications appeared in the August issue of JACS, printed with clear indication that our submission had been accepted first–then a psychologically significant point that a half-century later seems rather childish.

The 1951 Steroid Chemistry GRC brought face-to-face all the competitors in the race to synthesize cortisone, as well as other chemists and biochemists doing steroid research. One would imagine this to be a rather contentious and awkward event. But as I wrote in The Pill, Pygmy Chimps, and Degas’ Horse,
[a]lthough my story thus far would seem to illustrate the competitive aspects of scientific research, it does not disclose the collegiality and mutual esteem that even bitter competitors, like athletes or mountain climbers, display after an event. . . . One afternoon, the leaders of the various cortisone teams were reminiscing about the events of the past year. Our competitiveness and paranoia had been forgotten.
Our macho sense of humor, however, had not. My Wisconsin classmate Gilbert Stork (then at Harvard), Woodward, Sarett, and I concocted a communication to the editor of JACS titled “Synthesis of Cortisone from Neohamptogenin”–the latter a supposedly inexhaustible steroid precursor from New Hampshire maple syrup. In the end we got cold feet and did not try to get it by the Cerberus guarding the JACS gates.

For the next three years I was graced with the honor of chairing the conference. We abided by the Gordon Conference code that fostered collegiality and pioneering scientific work: each conference had fewer than a hundred scientists participating; each participant had his moment to strut his scientific chops, and then happily obtain the pummel of tough criticism he must absorb to obtain recognition from his colleagues; and time was always taken to breathe in lakeside air and engage in the human act of socialization. (I deliberately use the male gender since, to my shame, I do not recall a single female speaker!) The Gordon Conferences magically bring out the best in scientists whose imaginations are defined by their research and whose prides are entrenched in their achievements.