Gertrude Belle Elion

AMERICAN CHEMIST AND MEDICAL RESEARCHER
1918–1999

The Nobel Prize Committee rarely honors the work of scientists who develop new drugs. However in 1988, in awarding the Nobel Prize in physiology or medicine to Gertrude Elion and her colleague at the Burroughs

American chemist Gertrude B. Elion (right) with her colleague George H. Hitchings, recipients, with Sir James W. Black, of the 1988 Nobel Prize in physiology or medicine, "for their discoveries of important principles for drug treatment."

Wellcome Pharmaceutical Laboratories, George Hitchings, it recognized the work of this pair that led to the development of a series of important drugs, among these drugs used to treat malaria, the leukemias, viral infections, and some forms of impaired immune response.

Born on January 23, 1918, in New York City, Gertrude Elion graduated from Hunter College, in New York, in 1937 with an A.B. degree in chemistry. Unsuccessful in her efforts to enroll in graduate school, she worked for several years in pharmaceutical companies and as a teacher in New York City high schools while continuing her education part time. She earned an M.S. degree from New York University in 1941.

In 1944 Elion joined the Wellcome Research Laboratories, a subdivision of Burroughs Wellcome, as a senior research chemist; by 1967 she was head of their experimental therapy section. Probably the only woman to hold a top-ranking position in a major pharmaceutical company, in 1967 and for many years after, she is said to have felt that she experienced no discrimination at Burroughs Wellcome.

Her early work focused on the metabolism of nucleic acids. In 1944 little was known about these compounds beyond the fact that deoxyribonucleic acid ( DNA ) is the main component of the cell nucleus, and that DNA is composed of repeating units, called nucleotides, whose structures incorporate heterocyclic bases (that is, organic compounds with rings containing nitrogen atoms; the four bases involved are adenine , cytosine , guanine , and thymine ). Elion's hope was that an understanding of the synthesis of nucleic acids in normal cells (and eventual comparisons with nucleic acid synthesis in malignant cells and in disease-causing microorganisms) would suggest ways to block selectively the metabolism of cancer cells or of pathogens without harming normal cells. She therefore proceeded to synthesize a number of compounds that resembled and that might mimic the substance used in DNA synthesis and in this way might block the formation of DNA in harmful cells.

Working with 2,6-diaminopurine (2,6-DAP), a derivative of adenine, Elion found that it inhibited nucleic acid synthesis in cancer cells and was effective in treating mouse leukemia. During the early 1950s, following the elucidation of the structure of DNA, interest in nucleic acid metabolism became intensified, and scientists investigating it, including Elion and her group, found themselves at the forefront of biochemical research. Elion synthesized 6-mercaptopurine (6-MP), another derivative of adenine, which also inhibited DNA synthesis. It was approved by the U.S. Food and Drug Administration in 1953 for the treatment of acute childhood leukemia. Its success led her to probe its exact mode of action using newly developed radiochemical techniques, a breakthrough in drug-related research that advanced considerably the rational design of therapeutic agents. Elion studied 6-MP as a possible inhibitor of antibody-forming cells. As a result, its derivative Imuran (azathioprine) has been used as an antirejection drug in kidney transplants.

Other notable research by Elion led to the development of the antiviral drug Acyclovir (acycloguanosine), which has been used to treat the herpes simplex viruses. Her studies during the 1970s showed that Acyclovir inhibited viral replication by interfering with viral DNA synthesis. The subsequent development of AZT (azidothymidine), which works in much the same way as Acyclovir against the human immunodeficiency virus (HIV), was carried out at Burroughs Wellcome after Elion retired in 1983 (although she worked after 1983 as a consultant).

In addition to the 1988 Nobel Prize (which she shared with Hitchings and British scientist Sir James Black), Elion received other awards and several honorary doctorates. Active in public service, she served on both national and international health committees. She died on February 20, 1999, in Chapel Hill, North Carolina.

SEE ALSO Deoxyribonucleic Acid (DNA) ; DNA Replication ; Nucleic Acids ; Nucleotide .

Mary R. S. Creese

Bibliography

Alcamo, I. Edward (1997). "Gertrude Belle Elion (1918– )." In Women in the Biological Sciences: A Biobibliographic Sourcebook, ed. Louise S. Grinstein, Carol A. Biermann, and Rose K. Rose. Westport, CT: Greenwood Press.

Altman, Lawrence K. (1999). "Gertrude Elion, Drug Developer, Dies at 81." New York Times 148 (51,442; February 23):A21.

Goodman, Miles (1993). "Gertrude Belle Elion (1918– )." In Women in Chemistry and Physics: A Biobibliographic Sourcebook, ed. Louise Grinstein, Rose K. Rose, and Miriam H. Rafailovich. Westport, CT: Greenwood Press.