Pioneer of Rational Drug Design ... Gertrude Elion

Last Editorial Review: 12/30/2004

On February 21, 1999, Gertrude Elion, who won the Nobel Prize for Physiology of Medicine, died suddenly at age 81. She was born in 1918 in New York. While she was in her teens, her grandfather and mother died of cancer. Their deaths were to shape her lifelong interest in cancer treatment.

After she received a master's degree in chemistry from New York University in 1941, she tried to get a job as a scientist but women were not generally accepted as scientists at the time. Instead, she taught nurses. And then she tested pickles and berries for a food company.

Elion got her big break because there was a manpower shortage in the pharmaceutical industry during World War II. She was hired at Burroughs Wellcome as an assistant to Dr. George Hitchings in 1944.

Together with Dr. Hitchings, she began comparing normal human cells with cancer cells and pathogenic (disease-causing) organisms. Their aim was to discover differences in how nucleic acids (the building blocks of DNA and RNA) are metabolized in these diverse cells.

Elion and Hitchings exploited those differences in nucleic acid metabolism to create highly targeted drugs that selectively blocked the growth and reproduction of certain cancer cells and pathogenic organisms. This approach to drug development was entirely new. Elion and Hitchings did not just sit and screen randomly chosen molecules, as was commonplace at the time. They used their knowledge of nucleic acids to design new drugs.

The revolutionary approach of Elion and Hitchings led them to discover new drugs at a remarkable rate. Elion and Hitchings identified two important anticancer drugs, thioguanine and 6- mercaptopurine. Then pyrimethamine, a drug used successfully in the management of malaria. Next came an antibacterial drug in common use for urine infections, trimethoprim, followed by azathioprine. They discovered allopurinol, which blocks the formation of uric acid and is used to treat gout.

Elion's research group was involved in the discovery of acyclovir, a drug that selectively blocks the reproduction of herpes virus. The success of acyclovir disproved the assumption of many scientists who thought an effective and selective antiviral drug to be an impossibility. Scientists trained by Elion first saw the anti-HIV potential of AZT, which at the time was merely an unused anti-cancer drug.

We have not referred to her as Dr. Elion since she never finished her doctoral work! However, when she and George Hutchings shared the Nobel Prize in 1988, the Nobel committee noted that each of the drugs they had discovered was worth a prize in itself.

Source: Kent R, Huber B: Obituary: Gertrude Belle Elion (1918-99). Pioneer of drug discovery. Nature 398: 380, 1999.

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