Gertrude Belle Elion changed the way drugs are discovered with the new methodology that she and Hitchings created. They compared normal and abnormal cell metabolism and reproduction and then created antimetabolites to interfere with the life cycle of abnormal cells without harming normal cells. Elion focused on the purine bases (adenine and guanine), which are two of the four bases that are part of the larger nucleic acid (DNA) molecule, which carries genetic information.

Using this methodology in 1950, Elion synthesized a cancer drug, diaminopurine, which interfered with the metabolism of leukemia cells (abnormal white blood cells). It produced a complete remission in an acutely ill leukemia patient who had a relapse after two years and died. Saddened, Elion then made and tested over one hundred compounds. Finally, she substituted a sulfur atom for the oxygen atom on a purine molecule and made 6-mercaptopurine (6-MP), the first effective leukemia drug.

Elion's 6-MP (marketed as Purinethol in the United States) was the first childhood leukemia drug capable of causing a complete, though temporary, remission. Before the development of this drug, 50 percent of all children with acute leukemia died within three to four months. Eventually, a combination of 6-MP with other drugs could effectively cure childhood leukemia. By the early 1990's, the 6-MP therapy could cure 80 percent of patients with acute lymphoblastic leukemia.

6-MP also suppressed the immune system, which had implications for organ transplant surgery. In 1959, Robert Schwartz tested 6-MP on rabbits injected with a foreign compound, and the drug prevented their immune systems from producing antibodies. Then, the British surgeon Roy Calne used 6-MP on dogs receiving kidney transplants; the dogs given the drug outlived the dogs who did not receive 6-MP.

Elion remembered that she had synthesized azathioprine (Imuran), a complex version of 6-MP, and that this related compound did not affect cancer cells but was a better immunosuppressant than 6-MP. Calne then used Imuran for a successful organ transplant on a collie named Lollipop. Using the same drug, Dr. Joseph Murray performed the first successful kidney transplant between unrelated people in 1962. In the 1960's, Elion also developed allopurinol (Zyloprim), another compound related to 6-MP. This drug was effective for treating gout and many diseases occurring in South America.

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