23-2 CHF 2005 9/8/05 2:45 PM Page 8 George Rosenkranz (center) displays a test tube of yam-derived diosgenin, the substance needed to produce steroid hormones, and its raw source material, Mexican yams. Grouped around him from left to right are Alex Nussbaum, Mercedes Velasco, Gilbert Stork, Jan Pataki, Enrique Batres, Juan Berlin, Carl Djerassi, Rosa Yashin, Octavio Mancera, Jesùs Romo. CHF Collections. Courtesy of Roche. LifeLife afterafter SyntexSyntex By Alejandro Zaffaroni Early Years of age. My father was in the banking business, Alejandro Zaffaroni at My life started in Montevideo, Uruguay, many and our family enjoyed a good standard of living. CHF in 2004. Photo by years ago. Uruguay is a small country; today Early in my life, I lost both my parents. My Steven Begleiter. it has three million people. Back then life in mother passed away when I was 12 years of age, Uruguay was wonderful. It was a great place to and my father when I was 18. Now, when I look live—safe and peaceful—and the standard of back, I think that loss forced me to learn to be on living was high. For many years, Uruguay was my own. I was also lucky enough to have an uncle known as the Switzerland of South America. and an older sister who supported and encour- The social and political organizations were aged me to continue my education. very progressive: women were allowed to vote; After earning a B.Sc. at the University of it had the highest rates of literacy; it was the Montevideo in 1941, I began studying at the first social democracy on the continent; pri- school of medicine. I soon realized, however, that mary, secondary, and university education was anatomy was not one of my favorite courses. I (and still is) free. had taken some chemistry and biochemistry The population was and still is mainly of courses while in premed, and I decided to study European descent, mostly Italians and Span- biochemistry instead. Since there was no bio- iards. My grandfather emigrated from Italy chemistry degree in Uruguay or South America, TheThe EarlyEarly DaysDays and arrived in Uruguay when he was 16 years I started to inquire about studying abroad. of Syntex Continued on page 11 By George Rosenkranz Flashbacks from My Life The reaction of the owner, Angel Vieta, dean If I examine my early youth, I can detect hardly of the University of Havana medical school, was any signs of entrepreneurship. Sure, critical deci- negative. To quote: “In the 18 successful years at sions had to be made: first, to leave Hungary to my firm, I never had a chemist. Why should I hire study in Switzerland over the strong objections you now?” My answer was short and bold: “Give of my parents; later, to abandon my academic me a chance and I’ll show you.” career, my wonderful mentor, Leopold Ruzicka, Apparently impressed, he offered me the and the old continent for an essentially unknown glorious salary of $20 a week. I did not fail him. future. In retrospect, I consider the causes of A dozen products later, I was making $1,000 a these events, speaking in chemical terms, more month and 15% on those products’ sales. The the push-pull effect of the grave political circum- university offered me a professorship. I declined stances of that time than entrepreneurship. but eventually agreed to direct a research program When Pearl Harbor was attacked, I was in Summer 2005 Summer for Ph.D. candidates in my laboratories. The most 2005 Summer Havana waiting for a boat to Ecuador, where I famous of my two dozen students of those days George Rosenkranz at had been offered a chair in organic chemistry at was Ernest Eliel, who became a president of the CHF in 2004. Photo by Steven Begleiter. the University of Quito. After a futile wait, I de- American Chemical Society. 23:2 cided to take advantage of President Fulgencio My Zurich-born interest in steroids led me to 23:2 Batista’s decree allowing refugees to settle in look for domestic sources of steroidal sapogenins Cuba. And when the national university showed suitable for hormone synthesis. Finding none, I no interest in me, I tried to get a job at the largest imported sarsaparilla root from Mexico and made local pharmaceutical firm—Laboratorios Vieta- small quantities of progesterone and testosterone. Plascencia. Rumors of these activities led to an invitation to Chemical Heritage Chemical Heritage visit a start-up firm in Mexico named Syntex. Alejandro Zaffaroni (left) and Carl Djerassi discuss norethindrone, Chemical Heritage the first orally effective progestational agent and the first wholly Continued on page 10 synthetic hormone. Sold by Syntex as Norinyl. CHF Collections. Courtesy of Carl Djerassi. 8 9 23-2 CHF 2005 9/8/05 2:45 PM Page 10 The Early Days of Syntex Life after Syntex Continued from page 8 Continued from page 9 Syntex Going to the United States retire. The new head of our depart- utilized my paper chromatography On my arrival in Mexico I found a I managed to get a scholarship to come ment, Elmer Stotz, formerly of technique to produce cortisone at the small family enterprise dedicated to the to the United States thanks to the Insti- Harvard, told us at one of our first lowest cost and in the shortest time and manufacture of progesterone based on tute of International Education. My meetings that he was working on cy- thus was able to upstage all other methods of a brilliant but tempera- two options were Harvard University tochrome C and wanted all of us to “pharmas.” mental chemist, Russell E. Marker (see or the University of Rochester. work on his project. This created a To Mexico—and Back CH, Summer 1987, pp 3–6). However, I boarded a Liberty ship in Monte- problem for me because I had already The early years of Syntex in Mexico the owners had had a bitter falling-out video while World War II was still go- started working on my paper chroma- were a great experience for me. We with Marker, who left and shortly ing on and arrived in the United States tography idea and was convinced it were doing transformative science and thereafter set up a competitive venture. at the port of New York on 16 August would work out. I asked Stotz if I could had an incredible group of very smart In a burst of true entrepreneurial 1945, two days after the Japanese had still work on my own project on my and talented scientists. The progress we spirit, I accepted the offer to take over surrendered. For me, arriving in New own time at night, and he agreed. After made in the area of steroids made us the technical part of direction. My York at that time was an unforgettable a few months he reviewed my own realize that Syntex could become an compensation was roughly equivalent experience. It was like a big party: peo- work, saw that I was onto something, important company at the edge of new to the one in Havana but included the ple were celebrating in the streets; there and told me to forget about his project technology. Once we realized this po- option of buying 15% of Syntex stock was music; it was incredible. After a and to continue with my own work. I Russell Marker with his Syntex lab assistants, 1945. CHF Collections. Courtesy of Roche. tential, George and I started to trans- at book value. No big deal, since the couple of weeks I went on to Harvard. have always appreciated the opportu- form Syntex from a chemical company company was $330,000 in the red and Since profits selling hormones and There I met a young professor who ex- nity he gave me. Going Public into a pharmaceutical company. practically broke. For years to come, steroid intermediates were significant, plained my options. I would be part of I finished my Ph.D. in 1949 and The stage was set for the next big step in At one point, we realized that to my darling wife, Edith, and I faced the nobody questioned my budget. I in- a group of six students following a re- stayed at Rochester while I continued Syntex’s history: the change of owner- become a top-tier pharmaceutical com- dilemma of whether to buy a new vested in research, bringing the most search program under the guidance of my postdoctoral work. I developed a ship. This occurred when the legendary pany we needed to move to the United household item or invest in company talented scientists available to Mexico. the professor. paper chromatography technique that Wall Street entrepreneur Charles Allen States. Carl Djerassi, one of our distin- stock. Interestingly, organic chemists, in con- I then went to visit the University became very useful in the synthesis of decided to acquire the promising Mexi- guished Syntex scientists, had recently There were no manuals, no process trast to biologists, were more ready to of Rochester. During those times, the steroids; it allowed for much cheaper can upstart and eventually take it public. started teaching at Stanford University descriptions, and reagents and inter- assume risks. entire medical school was working on and faster analyses than the methods This group acquired 100% of the in Palo Alto, California. Carl encour- mediates bore coded labels. My staff The big exception was an outstand- the Manhattan Project. As a foreign developed by others at about the same Syntex stock for $2 million in cash and aged us to settle in Palo Alto.