Elion, Gertrude Belle (1918-1999)
American biochemist
Gertrude Belle Elion's innovative approach to drug discovery advanced the understanding of cellular metabolism and led to the development of medications for leukemia, gout, herpes, malaria, and the rejection of transplanted organs. Azidothymidine (AZT), the first drug approved for the treatment of AIDS, came out of her laboratory shortly after her retirement in 1983. One of the few women who held a top post at a major pharmaceutical company, Elion worked at Wellcome Research Laboratories for nearly five decades. Her work, with colleague George H. Hitchings, was recognized with the Nobel Prize for physiology or medicine in 1988. Her Nobel Prize was notable for several reasons: few winners have been women, few have lacked the Ph.D., and few have been industrial researchers.
Elion was born on January 23, 1918, in New York City, the first of two children, to Robert Elion and Bertha Cohen. Her father, a dentist, immigrated to the United States from Lithuania as a small boy. Her mother came to the United States from Russia at the age of fourteen. Elion, an excellent student who was accelerated two years by her teachers, graduated from high school at the height of the Great Depression. As a senior in high school, she had witnessed the painful death of her grandfather from stomach cancer and vowed to become a cancer researcher. She was able to attend college only because several New York City schools, including Hunter College, offered free tuition to students with good grades. In college, she majored in chemistry.
In 1937, Elion graduated Phi Beta Kappa from Hunter College with a B.A. at the age of nineteen. Despite her outstanding academic record, Elion's early efforts to find a job as a chemist failed. One laboratory after another told her that they had never employed a woman chemist. Her self-confidence shaken, Elion began secretarial school. That lasted only six weeks, until she landed a one-semester stint teaching biochemistry to nurses, and then took a position in a friend's laboratory. With the money she earned from these jobs, Elion began graduate school. To pay for her tuition, she continued to live with her parents and to work as a substitute science teacher in the New York public schools system. In 1941, she graduated summa cum laude from New York University with a M.S. degree in chemistry.
Upon her graduation, Elion again faced difficulties finding work appropriate to her experience and abilities. The only job available to her was as a quality control chemist in a food laboratory, checking the color of mayonnaise and the acidity of pickles for the Quaker Maid Company. After a year and a half, she was finally offered a job as a research chemist at Johnson & Johnson. Unfortunately, her division closed six months after she arrived. The company offered Elion a new job testing the tensile strength of sutures, but she declined.
As it did for many women of her generation, the start of World War II ushered in a new era of opportunity for Elion. As men left their jobs to fight the war, women were encouraged to join the workforce. "It was only when men weren't available that women were invited into the lab," Elion told the Washington Post.
For Elion, the war created an opening in the research lab of biochemist George Herbert Hitchings at Wellcome Research Laboratories in Tuckahoe, New York, a subsidiary of Burroughs Wellcome Company, a British firm. When they met, Elion was 26 years old and Hitchings was 39. Their working relationship began on June 14, 1944, and lasted for the rest of their careers. Each time Hitchings was promoted, Elion filled the spot he had just vacated, until she became head of the Department of Experimental Therapy in 1967, where she was to remain until her retirement 16 years later. Hitchings became vice president for research. During that period, they wrote many scientific papers together.
Settled in her job and encouraged by the breakthroughs occurring in the field of biochemistry, Elion took steps to earn a Ph.D., the degree that all serious scientists are expected to attain as evidence that they are capable of doing independent research. Only one school offered night classes in chemistry, the Brooklyn Polytechnic Institute (now Polytechnic University), and that is where Elion enrolled. Attending classes meant taking the train from Tuckahoe into Grand Central Station and transferring to the subway to Brooklyn. Although the hour-and-a-half commute each way was exhausting, Elion persevered for two years, until the school accused her of not being a serious student and pressed her to attend full-time. Forced to choose between school and her job, Elion had no choice but to continue working. Her relinquishment of the Ph.D. haunted her, until her lab developed its first successful drug, 6-mercaptopurine (6MP).
In the 1940s, Elion and Hitchings employed a novel approach in fighting the agents of disease. By studying the biochemistry of cancer cells, and of harmful bacteria and viruses, they hoped to understand the differences between the metabolism of those cells and normal cells. In particular, they wondered whether there were differences in how the diseasecausing cells used nucleic acids, the chemicals involved in the replication of DNA, to stay alive and to grow. Any dissimilarity discovered might serve as a target point for a drug that could destroy the abnormal cells without harming healthy, normal cells. By disrupting one crucial link in a cell's biochemistry, the cell itself would be damaged. In this manner, cancers and harmful bacteria might be eradicated.
Elion's work focused on purines, one of two main categories of nucleic acids. Their strategy, for which Elion and Hitchings would be honored by the Nobel Prize forty years later, steered a radical middle course between chemists who randomly screened compounds to find effective drugs and scientists who engaged in basic cellular research without a thought of drug therapy. The difficulties of such an approach were immense. Very little was known about nucleic acid biosynthesis. Discovery of the double helical structure of DNA still lay ahead, and many of the instruments and methods that make molecular biology possible had not yet been invented. But Elion and her colleagues persisted with the tools at hand and their own ingenuity. By observing the microbiological results of various experiments, they could make knowledgeable deductions about the biochemistry involved. To the same ends, they worked with various species of lab animals and examined varying responses. Still, the lack of advanced instrumentation and computerization made for slow and tedious work. Elion told Scientific American, "if we were starting now, we would probably do what we did in ten years."
By 1951, as a senior research chemist, Elion discovered the first effective compound against childhood leukemia. The compound, 6-mercaptopurine (6MP; trade name Purinethol), interfered with the synthesis of leukemia cells. In clinical trials run by the Sloan-Kettering Institute (now the Memorial Sloan-Kettering Cancer Center), it increased life expectancy from a few months to a year. The compound was approved by the Food and Drug Administration (FDA) in 1953. Eventually 6MP, used in combination with other drugs and radiation treatment, made leukemia one of the most curable of cancers.
In the following two decades, the potency of 6MP prompted Elion and other scientists to look for more uses for the drug. Robert Schwartz, at Tufts Medical School in Boston, and Roy Calne, at Harvard Medical School, successfully used 6MP to suppress the immune systems in dogs with transplanted kidneys. Motivated by Schwartz and Calne's work, Elion and Hitchings began searching for other immunosuppressants. They carefully studied the drug's course of action in the body, an endeavor known as pharmacokinetics. This additional work with 6MP led to the discovery of the derivative azathioprine (Imuran), which prevents rejection of transplanted human organs and treats rheumatoid arthritis. Other experiments in Elion's lab intended to improve 6MP's effectiveness led to the discovery of allopurinol (Zyloprim) for gout, a disease in which excess uric acid builds up in the joints. Allopurinol was approved by the FDA in 1966. In the 1950s, Elion and Hitchings's lab also discovered pyrimethamine (Daraprim and Fansidar) a treatment for malaria, and trimethoprim, for urinary and respiratory tract infections. Trimethoprim is also used to treat Pneumocystis carinii pneumonia, the leading killer of people with AIDS.
In 1968, Elion heard that a compound called adenine arabinoside appeared to have an effect against DNA viruses. This compound was similar in structure to a chemical in her lab, 2,6-diaminopurine. Although her own lab was not equipped to screen antiviral compounds, she immediately began synthesizing new compounds to send to a Wellcome Research lab in Britain for testing. In 1969, she received notice by telegram that one of the compounds was effective against herpes simplex viruses. Further derivatives of that compound yielded acyclovir (Zovirax), an effective drug against herpes, shingles, and chickenpox. An exhibit of the success of acyclovir, presented in 1978 at the Interscience Conference on Microbial Agents and Chemotherapy, demonstrated to other scientists that it was possible to find drugs that exploited the differences between viral and cellular enzymes. Acyclovir (Zovirax), approved by the FDA in 1982, became one of Burroughs Wellcome's most profitable drugs. In 1984, at Wellcome Research Laboratories, researchers trained by Elion and Hitchings developed azidothymidine (AZT), the first drug used to treat AIDS.
Although Elion retired in 1983, she continued at Wellcome Research Laboratories as scientist emeritus and kept an office there as a consultant. She also accepted a position as a research professor of medicine and pharmacology at Duke University. Following her retirement, Elion has served as president of the American Association for Cancer Research and as a member of the National Cancer Advisory Board, among other positions.
In 1988, Elion and Hitchings shared the Nobel Prize for physiology or medicine with Sir James Black, a British biochemist. Although Elion had been honored for her work before, beginning with the prestigious Garvan Medal of the American Chemical Society in 1968, a host of tributes followed the Nobel Prize. She received a number of honorary doctorates and was elected to the National Inventors' Hall of Fame, the National Academy of Sciences, and the National Women's Hall of Fame. Elion maintained that it was important to keep such awards in perspective. "The Nobel Prize is fine, but the drugs I've developed are rewards in themselves," she told the New York Times Magazine.
Elion never married. Engaged once, Elion dismissed the idea of marriage after her fiancé became ill and died. She was close to her brother's children and grandchildren, however, and on the trip to Stockholm to receive the Nobel Prize, she brought with her 11 family members. Elion once said that she never found it necessary to have women role models. "I never considered that I was a woman and then a scientist," Elion told the Washington Post. "My role models didn't have to be women—they could be scientists." Her other interests were photography, travel, and music, especially opera. Elion, whose name appears on 45 patents, died on February 21, 1999.
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