PRIESTLEY MEDAL
Stanford's Carl Djerassi Wins 1992 Priestley Medal Rudy M. Baum, C&EN San Francisco
Carl Djerassi, one of America's preeminent organic chemists, has been named the 1992 recipient of the Priestley Medal for his contributions to chemistry and society. The Priestley Medal is the American Chemical Society's highest award. The Priestley Medal will be, in a sense, an exclamation point that caps a distinguished career in chemistry that has spanned five decades. By the time he receives the award next year, Djerassi, who is a chemistry professor at Stanford University, will have retired as an active research chemist to pursue numerous other interests. These include research on public policy issues, writing fiction, and the Djerassi Foundation, an artists' colony located south of San Francisco. A colleague says of Djerassi that he "is a giant in chemistry" who "has established world reputations as a scientist many times over, as an industrialist with major successes, and as a humanitarian scientist with an extraordinary record of effort and achievement." Of Djerassi's most well-known achievement—the synthesis and development of the first oral contraceptive—the colleague says, "It is unquestionably one of the major triumphs of chemistry from a social as well as a financial viewpoint." On the day I interviewed Djerassi for this article, strong northwesterly winds had swept Northern California clean of any trace of smog. The spectacular vistas that define the San Francisco Bay Area were almost startling in their clarity. We met at Djerassi's office at Stanford, and he immediately suggested that we conduct the interview at SMIP Ranch, located about a half-hour's drive from the university. The ranch— 28
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1200 acres of steeply rolling terrain in California's coastal range encompassing open hills overlooking the Pacific Ocean and deep redwood canyons—has been Djerassi's retreat for the past 25 years. SMIP originally stood for "Syntex Made It Possible," a reference to the company with which Djerassi was associated for more than 20 years. Another interpretation of the acronym, which Djerassi attributes to Felix Bloch, is sic manebimus in pace (thus we'll remain in peace), a phrase that is carved into the wooden sign at the entrance to the ranch. It is a magical place, possessed of stunning vistas and towering redwood trees, and studded with the distinctly modern sculptures by prominent artists, many of them from California, that Djerassi has commissioned. Djerassi is a short, handsome man of 67, who has, in his own words, a "stiff" left leg, the result of a skiing accident in Europe during his youth that led, many years later, to a fused left knee. The infirmity hardly slows him down. He continues to ski, he has trekked in the Himalayas, and he strides confidently toward whatever destination he has set for himself. We stopped twice on our drive through SMIP to Djerassi's striking redwood and glass home. The first stop was to traipse across an open meadow to a bluff that is the site of a redwood Japanese temple gate by N o r t h e r n California artist Bruce Johnson. We also stopped to walk to a rough bench set into a boulderstrewn bluff that overlooks the Pacific. Djerassi says it is one of his favorite spots on the ranch. From here, one sees a number of the sculptures that dot the hillsides, the canyon where Djerassi's house is set, and miles and miles of hills tumbling down to the coast.
His son Dale, a filmmaker, lives in a house on the far side of one of the hills to the west. The former home of his daughter Pamela, an artist who committed suicide in 1978, lies in another draw to the south. Pamela's suicide led Djerassi, who had long been a patron of the arts, to establish the Djerassi Foundation. Djerassi says he is "pleased and surprised" about winning the Priestley Medal. Surprised, he says, because although he has won his share of awards over the years, none of the ACS awards he has received since moving to Stanford in 1959 "have had anything to do with my academic research." Rather, the ACS awards since 1960 have focused on his synthesis of the first oral contraceptive in 1951 at Syntex, and on his efforts to develop environmentally benign, biorational pesticides at Zoecon, a c o m p a n y c o f o u n d e d by Djerassi in 1968. Djerassi calls himself a "professional polygamist," a reference to the diverse scientific endeavors he has successfully pursued through his career. Carrying the metaphor further, he says, "If there was a favorite wife, however, it was my academic wife. Yet that is the work that here in the U.S. has never really been . . . recognized is the wrong word, but something like that. "I would like to think that the Priestley Medal is, to a certain extent, for those long-term research programs I worked on at Stanford for the past 30 years—chiroptical methods, mass spectrometry, artificial intelligence, and marine natural products." Djerassi was born in 1923 in Vienna. As he writes in his autobiography "Steroids Made It Possible," published last year as part of ACS's Profiles, Pathways, and Dreams series, "How did I get into chemistry? I
didn't have any childhood chemistry sets; I never blew up our basement; I never had chemistry in high school (in fact, I never graduated)/' Both his Bulgarian father and Austrian mother were physicians, and Djerassi assumed that he would follow in their footsteps. Djerassi left Vienna for Bulgaria after Hitler's Anschluss (annexation of Austria). He arrived in the U.S. with his mother in December 1939. His undergraduate career was compressed into five semesters: two at Newark Junior College, New Jersey, where a "superb" chemistry teacher, Nathan Washton, converted Djerassi from a premed major to a chemistry major; one at Tarkio College in Missouri, which happens to have been the alma mater of Wallace Carothers (the Du Pont chemist who invented nylon); and two semesters plus a summer at Kenyon College in Ohio, from which he received his bachelor's degree in 1942. He received his Ph.D. in chemistry from the University of Wiscon-
sin, Madison, in 1945, after only two years of study. A golden touch has characterized Djerassi's entire research career. After graduating from Kenyon College, not yet 19 years old, he worked for a year as a junior chemist at Ciba Pharmaceutical Products, Summit, N.J., in the laboratory of Charles Huttrer. Together, they discovered one of the first antihistamines, tripelennamine, which became the drug of choice for millions of allergy sufferers. At Wisconsin, Djerassi began what would become his lifelong intellectual love affair with steroids. He chose as his Ph.D. thesis project the partial aromatization of androgenic steroids to estrogens. As he writes in "Steroids Made It Possible," in the early 1940s this problem was of major practical significance because "testosterone was available industrially by partial synthesis from cholesterol, whereas estradiol still had to be extracted laboriously from pregnant mare's urine." Working w i t h his Ph.D. adviser, Alfred L. W i l d s , D j e r a s s i achieved the desired partial aromatization reaction. He and Wilds also coined the term "dienone-phenol rearrangement" to characterize a related aromatization reaction, a phrase that became the title of Djerassi's doctoral thesis as well as the accepted generic term for this type of reaction. Djerassi d e s c r i b e s many of his extensive scientific accomplishm e n t s in " S t e r o i d s Made It Possible." He writes, "Without a shred of embarrassment I acknowledge my intellectually polygamous nature." Thus, in his scientific career he has "been active in the development of new medicinal agents (antihistamines, oral contraceptives, and topical corticosteroids) that are still being used
by millions; the isolation, structure elucidation, and partial synthesis of several hundred natural products (steroids, lipids, terpenoids, alkaloids, and antibiotics); certain aspects of their biological function and biosynthesis; and, perhaps most important, the development of physical methods (such as optical rotatory dispersion, optical and magnetic circular dichroism, mass spectrometry, and computer artificial int e l l i g e n c e techniques) for the solution of stereochemical and structural problems." This research has led to the publication of more than 1100 papers and seven books of which Djerassi has been the author or coauthor. Djerassi believes that his most significant scientific contributions have been in the development of new methodologies for characterizing organic molecules. In his case, the techniques were usually first tested on steroid models, but the research was generally applicable to other organic compounds. Djerassi is largely recognized as having introduced modern chiroptical methods such as optical rotatory dispersion and circular dichroism into organic chemistry. The octant rule, which provides a rapid method for establishing absolute configurations of ketones without resorting to standards of known absolute configuration, evolved from these studies of steroids. This research continued into the early 1980s with the characterization by variable-temperature circular dichroism of chiral molecules in which the chirality is due solely to isotopic substitution. The studies produced the first quantitative estimates for the conformational preference of axial deuterium or carbon-13 over their hydrogen or carbon-12 counterparts. In the field of organic mass spectrometry, Djerassi and his coworkers have published nearly 300 papers and four books. They were pioneers in developing a detailed knowledge of the fragmentation behavior of organic molecules by using model compounds—which were frequently and not surprisingly steroids— and extensive isotopic labeling. Djerassi's text, "Mass Spectrometry of Organic Compounds," is still one of the most cited texts in this field. June 3, 1991 C&EN
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Priestley Medal In a collaboration with Joshua Lederberg and Edward Feigenbaum that dates back to the late 1960s, Djerassi has also played an important role in applying artificial intelligence techniques for structure elucidation of natural products. And for the past two decades, Djerassi and his coworkers at Stanford have focused on the characterization of novel marine sterols that have no counterpart in terrestrial organisms. They have isolated more than 100 marine sterols, and have carried out difficult underwater investigations of the biosynthesis of a number of such compounds. Efforts to understand the biological role of the marine sterols led to isolation and characterization of novel m a r i n e p h o s p h o l i p i d s . This turned out to be an unexplored area that led to numerous novel structures with significant bearing on biological membrane structure and function. The most recent research on mar i n e sterols, Djerassi says, has "pleased me enormously because it is an inadvertent completion of a circle" in his career as a chemist. The first oral contraceptive synthesized—in Syntex's Mexico City research laboratory—was 17a-ethyn y l - 1 9 - n o r t e s t o s t e r o n e . At t h a t time, 19-norsterols were unknown in nature, Djerassi points out. It t u r n s o u t , h o w e v e r , t h a t 19norsterols are common in many sponges, where they replace cholesterol. The thesis research of Djerassi's final Ph.D. student was the complete characterization of t h e b i o s y n t h e s i s of these compounds. The paper describing this research, Djerassi notes, will be the last paper he submits to the Journal of the American Chemical Society. In addition to his research, Djerassi says, "I have always been extremely interested in collaborations w i t h scientists from developing countries." That interest stems from the first two-year stint he spent working in Syntex's Mexico City laboratory and supervising the work of a dozen or more Mexican colleagues, years he calls "among the most productive ones of my chemical career." While at Syntex, Djerassi 30
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became involved with the Instituto de Quimica of the National University of Mexico. All of the institute's research expenses were borne by Syntex, and most of the original staff members were trained in one way or another by Syntex. In 1957, during Djerassi's second three-year period in Mexico City, then as Syntex's research vice president, the company instituted an industrial postdoctoral fellowship program in which numerous chemists have participated. Contacts between Djerassi and a number of Brazilian chemists eventually led to the establishment of the National Academy of Sciences' U.S.Brazil chemistry program. Djerassi chaired the program for its first several years, and he convinced a group of senior U.S. chemists, among them Henry Taube, Harry Gray, William Johnson, Charles Overberger, John Baldeschwieler, and George Hammond, to become involved with the program. Djerassi participated in numerous Pugwash Conferences in the 1960s and 1970s. In 1967, at the 17th Pugwash Conference on Science & World Affairs, he presented a paper on his Mexican and Brazilian research experiences entitled "A High Priority? Research Centers in Developing Nations." In it, he outlined how a basic research center might be established in a country where no
such centers existed and where t h e r e w e r e n o t yet e n o u g h trained scientists available to staff it. This proposal eventually led to the creation of the International Centre for Insect Physiology & Ecology (ICIPE) in Nairobi, Kenya, which Djerassi calls "one of the most remarkable examples of international cooperation by academies." NAS, the American Academy of Arts & Sciences, the Royal Society of London, the Royal Swedish Academy of Sciences, and the Max Planck Gesellschaft cooperated in the creation and continued operation of ICIPE. But, as Djerassi notes, as far as chemistry is concerned, "it is late in the game for me," and our conversation at SMIP focused largely on other interests. Djerassi now lives on the Stanford campus with his third wife, Diane Middlebrook, who is an English professor at Stanford. SMIP Ranch, where he lived for a number of years after his divorce from his second wife in 1976, remains a sanctuary where he can work undisturbed by the outside world. His home, designed by Gerald McCue, who is now the dean of Harvard's School of Architecture & Design, a n d his p a r t n e r Frank Tomsick, is all redwood and glass, light and angles. Outside the dining area, in a clearing between the house and the redwood trees that surround it, is a kinetic sculpture by New York artist George Rickey. During a break in our interview, I gazed at t h e s p i d e r y , m o v i n g , stainless steel arms of the sculpture, glinting sunlight dappling t h r o u g h the redwood branches. This spot is a special one; it casts a spell over an observer. After touring the house and grounds with Djerassi, I realized that it contains a dozen such places, specifically located to take advantage of an angle of sunlight, a view of a cluster of r e d w o o d s , or t h e e v e r - p r e s e n t wind rushing in from the ocean. In 1985, Djerassi was operated on for colon cancer. An adamant nonsmoker, Djerassi says, "I always considered myself a very healthy person. Suddenly, I wasn't." During his recuperation, "I came to terms with
Numerous works by resident artmy own mortality. I asked myself however, he is working on a novel whether I would have lived a differ- that does not involve science at all ists are in place in the redwood ent life if five years earlier I had because, he says, "I don't want to be forests and on the open hills of known I would come down with typed. I don't want people to say the SMIP. Djerassi notes with a smile cancer. It took very little reflection only thing I can write about is scien- that on three occasions Cornell to answer in the affirmative." The tists." The new novel, provisionally University chemist and Nobel Launext question, he says, was obvious: entitled "The Other Marx," deals reate Roald Hoffmann has been in residence at SMIP as a poet. "PeoK n o w i n g what he knew then, with writers and critics. would he lead a different life in the In addition to his scientific autobi- ple at Berkeley and Stanford didn't coming five years? The answer, ography, "Steroids Made It Possi- know that their famous theoretical again, was yes. ble," Djerassi has completed his colleague was only 30 minutes He decided that his goal was not memoirs, "The Pill, Pygmy Chimps, away," he laughs. to do more science. So over the past and Degas's Horse," which will be At the conclusion of our interseveral years he has been engaged released in 1992. "I have always en- view, Djerassi suggests that we in an orderly process of closing his joyed reading biographies and auto- drive to the program's studios, lolaboratory at Stanford. That process biographies, and I have read those cated in the renovated, 12-sided will be completed later this year. of quite a number of scientists," he ranch barn. We take my car and Djerassi will continue to teach un- says. "I find the vast majority of drive up over a steep, windswept dergraduate courses in Stanford's them tell you nothing about the per- hill, and down into a sunny draw human biology program. And he son. I think this is very important to the studios. Pamela Djerassi's plans to participate in a major com- for the public to know." Djerassi former home is a short distance parative study of the U.S. and Japa- suggests that the unwillingness of away; it now serves as the program nese pharmaceutical industries be- many scientists to reveal themselves director's residence. As we drive, ing carried out at Stanford. Djerassi as complete human beings is a major Djerassi talks briefly of his daughwill focus on birth control ter's s u i c i d e , an e v e n t in the two nations. about w h i c h he w r o t e movingly in "A Scattering One of the principal activof Ashes," an essay pubities Djerassi decided to foI would like to think that the lished earlier this year in cus on as an alternative to the Hudson Review. Priestley Medal is, to a certain extent, chemistry was writing. He At the studios, we enwould use his knowledge of for those long-term research programs counter two young Polish science and scientists to artists with whom Djerassi write in a genre he calls I worked on at Stanford plans to meet later in the "science-in-fiction." "The for the past 30 years day to discuss an environidea of doing something mental sculpture they very different intellectually would like to erect at a locathat draws on my life as a scientist is very exciting," Djerassi factor behind the skewed view of tion on the ranch. The smell of says. scientists held by many nonscien- wood smoke is in the air—hundreds He had already published a num- tists. Djerassi has also published po- of rough-hewn, charred wooden ber of short stories over the years in ems in literary journals, and his first hearts, each about a foot in diameter literary magazines. They have now collection, "The Clock Runs Back- and two inches thick, are stacked been collected into a paperback edi- wards" (C&EN, May 13, page 56), outside the studios. The hearts are destined to be part of an artwork, tion, "The Futurist and Other Sto- was published early this year. ries." In 1989, he published his first His other abiding passion is the the final shape of which I can only novel, "Cantor's Dilemma," a darkly Djerassi Foundation's Resident Art- guess. Most of the resident artists comic tale that explored a variety of ists Program. Established in 1979 in are at lunch, so we can tour a numethical issues that scientists face. memory of his daughter, Pamela, ber of studios without disturbing "Cantor's Dilemma" was generally and now located at SMIP Ranch, the them. Djerassi escorts me through well received critically, and it has program provides an opportunity the facilities with obvious pride. I been translated into German, Japa- for creative artists to work together have been on tours like this through nese, and Spanish. in excellent studio facilities for peri- innumerable chemistry laboratories Djerassi has since completed a sec- ods of from two weeks to three following interviews, tours that ond novel, "The Bourbaki Gambit," months. The program is unusual were conducted by chemists justifiwhich deals with problems faced by among resident artists programs in ably proud of the research environaging academic scientists in the U.S., that it includes dance and perform- ments they had created. This tour of Japan, and Europe, as well as the im- ing arts in addition to literature, mu- a composer's studio, a darkroom, a portance of peer recognition in sci- sic, and visual arts. More than 500 painter's studio, and a large, enence. Djerassi plans to write a third artists have participated in the pro- closed performance area seems enscience-in-fiction novel that will ex- gram since its inception, and it has tirely appropriate, my guide this amine the role of scientists in the become the largest artists' colony time a renowned chemist who has turned his gaze to new frontiers. • public policy process. Currently, west of the Mississippi River. June 3, 1991 C&EN
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