November 2009

Cecil Pickett: Advancing Drug Metabolism and Discovery

rat liver glutathione s-transferase
Three-dimensional image of a dimer of rat liver glutathione S-transferase 3-3, a member of the GST family of drug-metabolizing enzymes. Biochemistry (1992) 31, 10169-10184.

Although his undergraduate days were a bit trying, Pickett’s next destination, graduate school at the University of California, Los Angeles, was the exact opposite: total fun. “I couldn’t believe they actually paid me to go to school,” he says. “I could now spend all of my time actually focusing on my research or the classes I was taking.”

That research would entail looking at the heterogeneity of mitochondria and their interaction with the endoplasmic reticulum, under the guidance of Joseph Cascarano. Pickett notes that Cascarano was demanding as a mentor and expected a lot of his students, but Pickett was quite comfortable with demanding schedules. After completing his Ph.D. in 1976, Pickett even spent two more years as a postdoctoral fellow at UCLA, working with Cascarano and Verne Schumaker in the chemistry department.

Into the Breach of Industry

As he was deliberating his next career move, Pickett became very interested in a particular Journal of Biological Chemistry paper he had come across that discussed the conversion of preproalbumin to proalbumin. The corresponding authors on that paper were Al W. Alberts and P. Roy Vagelos, who worked at the Merck, Sharp & Dohme Research Laboratories.

“I remember seeing that affiliation and not even realizing that it represented a pharmaceutical company,” Pickett says. “In graduate school, I wasn’t really educated about the potential of doing research in industry, so the name didn’t mean that much to me.”

Still, Pickett decided to write a letter to Vagelos and ask if he could join his laboratory; he was startled when he later found out exactly what Merck was but also was pleasantly surprised when he received an offer to join the company. “Cascarano was very influential in my decision to accept the offer,” Pickett says. “He had done an internship with a pharmaceutical company, so he was familiar with the culture of industry. And, although he hoped I would consider staying in academia, he told me that Merck would be a good place to work, because they had a strong history of supporting science.”

Pickett soon would experience this supportive culture firsthand. At one of the first meetings he had with Alberts and Vagelos, the recently appointed head of Merck Research Laboratories, he was told to respect the company’s long-term goals and interests but that he should not be afraid to try to establish his own career and pursue his own interests.

“I found that very enlightening,” Pickett says. “But I think Vagelos was ahead of the curve in that he understood that individuals given the freedom to be creative often come up with the initial discovery that eventually leads to a new drug, and he made a concerted effort to seek out talented people in academia to fill out positions in Merck. I feel extremely fortunate that I was chosen near the forefront of that effort.”

Pickett was also fortunate in that scientist Anthony Y. H. Lu had just joined Merck.

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