A Science Odyssey
People and Discoveries

Drugs developed for leukemia

Gertrude Elion (b. 1918) found out about the Burroughs Wellcome drug company through her father, a dentist; the company had sent a drug sample to his office. Elion had graduated at the top of her class at Hunter College in 1937, but due to the Depression and the fact that she was female, she had trouble finding a job where she could apply her chemistry training. She had temporary and part-time jobs and took courses toward a masters degree, but kept hoping for a real research opportunity. In 1944, on her father's suggestion, she went to Burroughs Wellcome for an interview. George Hitchings (b. 1905) hired her on the spot for $50 a week.

Hitchings' research team was launching an investigation of nucleic acids. At that time, little was known about them. Oswald Avery had recently discovered that they were part of DNA, and carried genetic information. But the structure of DNA and the nucleic acids' exact function would not be known for another decade. Hitchings split the nucleic acids up among his assistants. Elion was assigned a subgroup called purines. (Two of the four bases in DNA are purines -- adenine and guanine.) Hitchings reasoned that since bacteria, tumors, and certain parasites need large amounts of nucleic acid to reproduce, you could interrupt their life cycles by interfering with the nucleic acid. With that goal, he gave his researchers freedom to pursue the problem.

Elion created hundreds of purine compounds and investigated how they worked. Within two years, she was publishing papers on her findings. The breakthrough year was 1950. She created a purine chemical that disrupted the formation of leukemia cells. It was tested on animals successfully and then on humans. It brought about complete remission, but patients all eventually relapsed and died.

Elion was now riveted by cancer chemotherapy. She found that by minutely altering one of the compounds, it stopped tumor growth in mice. This was 6-mercaptopurine, or 6-MP for short. It was rapidly approved for use in childhood leukemia. Again it caused remission, but did not cure the disease. Eventually doctors would learn to use 6-MP in combination with other drugs and reach a cure rate of about 80 percent.

Meanwhile, in 1958, other researchers had found that 6-MP could also interfere with the immune system. That was a good thing when it came to organ transplants. Elion and Hitchings gave one of these researchers a chemical that they had synthesized -- a close relative of 6-MP that was later called azathioprine (trade name Imuran). When the British researcher told them the results were "not uninteresting," Hitchings was delighted. He knew that, "translated from the British, he had a very exciting result." Imuran worked in organ transplants with dogs. By 1961, kidney transplants on humans were attempted, and soon, with the help of Imuran, patients were surviving.

Looking further into the purine chemicals, and refining those she had made, Elion also developed drugs to treat gout and a few South American parasitic diseases. After Hitchings' retirement in 1967, Elion became head of the Department of Experimental Therapy, and turned back to an idea from 20 years before: a drug to treat viral infection. People thought it couldn't be done, but in the early 1970s Elion's team developed acyclovir (trade name Zovirax), effective against herpes, shingles, and Epstein-Barr virus. Elion retired in 1983 and within a year her former unit used her methods to develop AZT, the first drug licensed in the United States to treat HIV. In 1988 Elion, Hitchings, and Sir James Black of London received the Nobel Prize in physiology/medicine. The Nobel committee said of the recipients, "While drug development had earlier mainly been built on chemical modification of natural products, they introduced a more rational approach based on the understanding of basic biochemical and physiological processes."

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