Gertrude Belle Elion (1918-1999).

Abstract

G ertrude Elion, a pioneer in drug development and one of only 11 women scientists to win the Nobel Prize, earned her master's degree in chemistry from New York University in 1941. She found work teaching nurses and testing food products—finding employment as a research scientist was difficult for women in those days. Her opportunity came with the arrival of the Second World War and the diminished supply of male scientists. She was hired by the Burroughs Wellcome Company to work as a research assistant in the laboratory of George Hitchings. And so began a collaboration that would last for Elion's entire career. Elion and Hitchings started to investigate the mechanisms of purine and pyrimidine metabolism and the incorporation of these building blocks into nucleic acid. By exploring the effects of incorporating purine and pyrimidine structural analogs into DNA—a revolutionary approach—they discovered a long list of extremely important drugs: thioguanine and 6-mercaptopurine for treating acute leukemia, pyrimethamine for malaria and toxoplasmosis, and the antibacterial trimethoprim. Next came azathioprine, an immunosuppressive drug that improved the success of renal transplantation and the treatment of autoimmune disease. They developed the first truly effective antiviral compound: acyclovir for the treatment of herpesvirus infection. Further studies of the antiviral effects of pyrimidine and purine analogs led to the discovery of AZT, the first drug for HIV. These discoveries were triumphs of rational drug design based on the exploration of metabolic pathways. In recognition of their work, Elion and Hitchings (together with James Black) were awarded the 1988 Nobel Prize for Physiology or Medicine. Worldwide recognition of Trudy Elion's role as a pioneer in rational drug design and as an articulate spokeswoman for science continued to grow even after her formal retirement from Burroughs Wellcome in 1983. To the end of her life she maintained a demanding travel schedule, which she pursued not for personal reward but for the opportunities her travels provided to promote the cause of science and to encourage those just beginning a career in research. It was at the end of her magnificent career with Burroughs Wellcome that Trudy's association with Duke University in Durham, North Carolina, began. Trudy enthusiastically accepted an offer to join the faculty at Duke in a part-time appointment to work with and mentor medical and graduate students. From 1983 until the end of her life, Trudy served as a mentor for many medical and graduate students in the neuro-oncology and pediatric bone marrow transplant programs. Despite her hectic travel schedule, Trudy spent a great deal of time with her students and was an inspiration to them all. During her years at Duke, she published more than 25 papers with her students and taught them invaluable lessons about how to do science and, just as important, why to do science. Trudy regularly attended the American Association for Cancer Research annual meetings where the students presented their work, and she made a point of being at their presentations whenever possible. Most of her students are now pursuing successful careers in academic medicine. All of them remember the experience of working with a Nobel laureate who was brilliant and insightful, as expected, but who was also stimulating, supportive, and inspirational. Trudy's material rewards for this effort were meager—a small stipend and a modest office—but she never asked for more. Ironically, she was looking forward to moving into a much larger and nicer office—with two windows—but died the evening before the move. We know that Trudy enjoyed her career with our students, and we know that her mentorship was a career highlight for them. But perhaps the greatest beneficiaries of her time at Duke were the faculty and staff, especially those of us who worked most closely with her, who were able to know and learn from a most gracious person and a brilliant and determined scientist.