Pioneering the Pill

Most people experience at least one event that changes the direction of their lives. For George Rosenkranz-the man who made "the pill" possible-it was a stopover in Cuba. In 1941, he was on his way by boat from Switzerland to a position as a professor of Organic Chemistry at the University of Quito in Equador. But the ship that was scheduled to pick him up in Cuba never came. Pearl Harbor had been bombed, and the world changed. So Rosenkranz-stranded on the island-went to work for a pharma company.

Even with a degree in chemical engineering from the Swiss Federal Institute of Technology in Zurich, Rosenkranz claims that, starting out, "I had no knowledge of the pharmaceutical industry." Of his first effort to develop a compound, he says, "I went eeny, meeny, miny, mo; threw in a little chemical reasoning; and dreamt up a formula." The product, an oil soluble bismuth preparation for sexually transmitted diseases-penicillin was not available yet-was a "tremendous success." His salary took a huge leap, and he acquired the confidence to begin pursuing his own line of study: synthesizing hormones.

George Rosenkranz

His first step was to collect wild yams, which he discovered did not grow in Cuba. So he had students in Mexico and Peru find them and ship them to him. From those inedible vegetables, he made small quantities of progesterone and testosterone. Syntex, a Mexican company that was trying to synthesize hormones, heard of his work and offered him a position. The pharma company "was in shambles and nearly bankrupt," he says. Its lead R&D person had departed, leaving all his work in a code no one could decipher.

In 1945, Rosenkranz moved to Mexico and took on the job with the attitude, "Life is too short, I have my own methods, let's get to work." Within two months, he developed a process for synthesizing progesterone from a wild Mexican yam root called barbasco, and Syntex was back in business. Next, he proceeded to develop industrial syntheses for all of the sex hormones-male and female-except estrone.

A brief look at George Rosenkranz's background and accomplishments:

At the time, Mexico lacked a PhD program in chemistry, so Rosenkranz recruited researchers from Mexico and around the world. When asked how he accomplished that with a start-up budget, he replies simply, "Charm."

Among those he persuaded to join Syntex were Carl Djerassi, a young Austrian refugee who was already well known for his research and writing, and Alejandro Zaffaroni, who became Rosenkranz's lifelong friend and later founded Alza (now a J&J company) and Affymetrix. Rosenkranz put the team to work with the charge of producing a full line of hormones.

One of its first successes was to beat Big Pharma in the highly publicized quest to synthesize cortisone, an animal-derived steroid used to relieve the pain and inflammation of arthritis. Being first to market with a blockbuster product-Synalar, a topical corticoid-gave Syntex the revenue, stability, and worldwide reputation it needed to further its groundbreaking R&D. Then the team became the first scientists to develop a process for producing norethindrone, which would become the active ingredient in birth control pills.

But in the 1950s, birth control was a controversial concept. After a 1957 FDA approval of norethindrone for menstrual disorders, Syntex's US marketing partner, Parke-Davis, got cold feet about manufacturing a product that religious groups opposed and refused to publish or release its norethindrone studies. So, in 1960, Searle, with a nearly identical hormone, norethynodrel, was first to market the product that revolutionized family planning. Later, Syntex joined Ortho in marketing norethindrone as a contraceptive and was a major player in the US birth control market for nearly 40 years.

George Rosenkranz, Syntex CEO, with his lifelong friend, Alex Zaffaroni (left), founder of Alza(1955).

The next big breakthrough for Rosenkranz's team was the development of the anti-inflammatory Naproxen, a pain management therapy. Syntex launched it in 1973, and to this day, it is recommended by pharmacists more often than any other. By then, Rosenkranz had been named president and CEO, a position he held for 25 years.

"I was absolutely sold on, and I still believe in, participating management," he says. "I always inquired and listened to everyone's opinions, but in the end, I made the final decision. You have to remember that the information you receive is always biased. People have their own agendas. One thing I learned is that to be a CEO is a very lonely job."

During his tenure, Syntex established operations in Canada, the United States, the United Kingdom, France, Spain, and Belgium, growing into a diversified pharma giant with a $5.3 billion market capitalization. It also funded and helped create an advanced degree program at the National University of Mexico's Instituto de Quimica. In its early years, the program's students could fulfill undergraduate thesis requirements through research they conducted at Syntex.

Rosenkranz remained Syntex's chair of the Science Committee and was elected to the honorary position of founding chairman until Roche bought the company in 1994. The acquisition left him with mixed emotions. "Syntex was dismantled," he laments. "There are no products, no divisions. But Roche is an important company, and only they know the real purpose behind the acquisition of Syntex." On the subject of industry consolidation, Rosenkranz says, "I don't believe big is beautiful."

Although technically retired for the past 20 years, Rosenkranz is still active in the industry. He is a member of the board of Digital Gene Technologies and president of the advisory board of ICT Mexicana, an organization that merges the goals of science and industry. His scientific interest has shifted slightly from hormones to pheromones, and his favorite role is that of consultant to Pherin Pharmaceuticals in Menlo Park, California, where he provides guidance in the design and screening of vomeropherin compounds.

"Pheromones have tremendous CNS [central nervous system] activities," he says. "I synthesized the first of those substances 50 years ago in the laboratory. It turned out to be a very interesting compound, and there's clinical work being done now in different areas. One of which is premenstrual tension, and that project is in Phase III. Pherin also has an agreement with a large Dutch pharmaceutical company, Organon.

Rosenkranz, who was born in Hungary, educated in Switzerland, and lived in Mexico for 66 years, speaks six languages. He is an active world-class bridge player who has won many US and Mexican national championships and authored 14 texts on the subject. At 85, in addition to his consulting job, he still works out at the gym, plays the piano, and writes. He divides his time between Mexico City and Mountain View, California, where he is a neighbor of Zaffaroni. "We get together at least twice a week," he says. "We kick around problems, look at new adventures, talk about science, and generally play the role of devil's advocate."

Last year, Mexico's President Vincente Fox awarded Rosenkranz the "Condecoracion Eduardo Liceaga," the country's highest award for contributions to the health field.