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Wednesday, October 3, 2012

Gertrude Belle Elion

 

The American biochemist Gertrude B. Elion (1918-1999) won a Nobel Prize for her scientific discovery of drugs to treat leukemia and herpes and to prevent the rejection of kidney transplants.
Born in New York City in 1918, Gertrude Elion graduated from Hunter College with a B.A. degree in chemistry in 1937. In the midst of the Great Depression it was difficult for a woman to find a job in science. Elion had decided while still in high school to become a cancer researcher but for several years worked as a lab assistant, food analyst, and high school teacher while completing her Masters degree at night. She received an M.S. in chemistry from New York University in 1941.
During World War II, women were needed in scientific laboratories and Elion was hired as a biochemist by the Wellcome Research Laboratories, then in Tuckahoe, New York. There she worked for many years with George Herbert Hitchings, co-recipient with Gertrude Elion of the Nobel Prize for Physiology or Medicine in 1988. Together, they pioneered pharmaceutical research, discovering and developing drugs to treat previously incurable diseases. Elion was later promoted to senior research chemist and in 1967 became head of the Department of Experimental Therapy.
The theory behind the development of these new drugs suggested by Hitchings was that, since all cells require nucleic acids, one might be able to stop the growth of rapidly dividing cells such as bacteria and tumor cells by substituting false building blocks, or antagonists of nucleic acid bases, in the synthesis of nucleic acids. Thus the replication of the unwanted cells might be prevented. Elion set to work especially on purines, nitrogenous bases that are important constituents of DNA. She was also working part-time on her doctorate at Brooklyn Polytechnic Institute but, given the ultimatum to choose between continuing on her doctorate full-time and keeping her job, she chose the latter. She was later awarded honorary doctorate degrees from George Washington University and several other universities and colleges in recognition of her research.
The early research involved a bacterium, Lactobacillus casei, which could synthesize purines given the right chemical substrates. She found her research work fascinating because so little was then known about how nucleic acid was synthesized. James Watson and Francis Crick had not yet determined the structure of DNA, the double helix. The pathways for biosynthesis of purines were not worked out until the mid-1950s by Arthur Kornberg and others.
By 1951 Elion and Hitchings succeeded in developing a number of drugs that interfered with purine utilization called purine antimetabolites. Two of these were tested at the Sloan-Kettering Institute and were found to be active against leukemia in rodents. One of these, 6-mercaptopurine (6-MP), was then tested on children with acute leukemia at ten American medical centers. At that time there were no effective drugs for these terminally ill children and not even one in three lived as long as one year. The drug 6-MP was found to produce complete, though often temporary, remission. It was approved by the Food and Drug Administration in 1953. The success of this and related purine antimetabolite drugs opened up a whole new area of research in leukemia chemotherapy. Although 6-MP is still widely used, it is now prescribed in combination with several other antileukemic drugs. Almost 80 percent of children with acute leukemia can now be cured.
In the process of studying how 6-MP worked in both animals and humans, Elion developed a closely related compound called azathioprine. It was tested first as an anticancer drug but was later found to have a quite different but important function: it blocked the immune response leading to the rejection of foreign transplants. In 1960 this drug was tried out successfully in a kidney transplant on a collie. By 1962 successful human kidney transplants from unrelated donors became a reality, using azathioprine as an immunosuppressant drug. Cyclosporine made possible successful transplants of livers, hearts, and lungs, but azathioprine is still used in kidney transplants. It is also used to treat other serious diseases such as severe rheumatoid arthritis and systemic lupus.
Another drug that Elion and her coworkers synthesized scientifically--that is, by understanding how it works biochemically--is allopurinol. It can be used for the treatment of gout and other diseases resulting from an excess of uric acid. In gout uric acid crystals accumulate in the joints, causing extreme pain. Allopurinol inhibits the formation of the uric acid.
In 1968 Elion and her group returned to some early work she and Hitchings had done on antiviral drugs. They developed a drug found to be highly active against herpes virus. In 1970 their laboratory moved to North Carolina where they synthesized a new antiviral agent, Acyclovir. This drug is highly effective against several types of herpes virus and is not toxic to normal cells. It has been used in treating herpes since 1981, and also in treating patients with the painful disease known as shingles, caused by the varicella-zoster virus. It has even been a lifesaving drug for patients with herpes encephalitis, a frequently fatal disease. Acyclovir, approved by the Food and Drug Administration 1984, has become one of Burroughs Wellcome's most profitable drugs. Two years later, researchers trained by Elion and Hitchings developed azidothymidine, or AZT, the first drug used to treat AIDS.
Elion retired from Burroughs Wellcome in 1983 but remained there as a scientist emeritus. She served as president of the American Association for Cancer Research in 1983-1984 and on many advisory boards, including chairman of the Steering Committee on the Chemotherapy of Malaria. She also served as research professor of medicine and pharmacology at Duke University, working with advanced medical students who wish to do research on tumor biochemistry and pharmacology sharing her interest and experience.
In 1988, Elion and Hitchings shared the Nobel Prize for physiology or medicine with Sir James Black, a British biochemist. In her Nobel Prize speech, Elion noted that her 40 years of research not only resulted in many therapeutic drugs but that these life-serving agents have been tools to understand nature's mysteries. They led her into whole new areas of medical research, not only in biochemistry and pharmacology but also in immunology and virology.
Elion celebrated a momentous year in 1991 as she became the first woman to be inducted in the National Inventors Hall of Fame. She was also named to the Engineering and Science Hall of Fame and received the National Medal of Science. In 1995, she was named the Higuchi Memorial Award winner and lectured at the University of Kansas. Elion, who held 45 patents, died at the University of North Carolina Hospital in Chapel Hill, North Carolina, on February 21, 1999


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