Gertrude Elion and the Rational Design of Modern Drugs

Gertrude Elion was born in New York City on 23 January 1918. She never completed a doctorate, yet she shared the 1988 Nobel Prize in Physiology or Medicine, awarded for discoveries of important principles for drug treatment.

Family and a reason to study chemistry

Her father, a dentist, had come to the United States from Lithuania at the age of twelve. Her mother came at fourteen from a part of Russia which, as Elion put it in her autobiography, became Poland after the war. According to the Jewish Women’s Archive, her father came from a long line of rabbis, and Elion attributed her parents’ emphasis on education to their Jewish background.

When she was fifteen her grandfather died of cancer. She decided then to work against the disease. She entered Hunter College in 1933 and studied chemistry. Her father had lost heavily in the stock market crash of 1929, and Hunter was free to students whose grades were good enough; Elion later wrote that without it she might never have received a higher education. She graduated in 1937.

Looking for work

Because of the Depression she could not go on to graduate school, although she applied to several universities for an assistantship or fellowship. Jobs were scarce, and she found that the few laboratory positions available were not open to women. She briefly enrolled in secretarial school, and after a short job at a nursing school she began working without pay as an assistant in a chemist’s laboratory. The accounts of how long she went unpaid differ: the Science History Institute says she was put on the payroll after six months, while her autobiography says she stayed a year and a half and was finally earning $20 a week.

With her savings and help from her parents she entered graduate school at New York University in 1939, the only woman in her graduate chemistry class. She supported herself by working as a substitute teacher, and according to the Science History Institute and the Women of Valor page first as a doctor’s receptionist, and did her research at night and on weekends. She received a master’s degree in chemistry in 1941.

During the Second World War, with chemists in short supply, she did analytical quality-control work for a food company for about a year and a half. She then moved to a research laboratory at Johnson & Johnson, which closed after about six months.

Burroughs Wellcome

In 1944 she joined the drug company Burroughs Wellcome as assistant to George Hitchings. She began studying for a doctorate at night at Brooklyn Polytechnic Institute, but when she was told she would have to study full time, she chose to keep her job. She never completed a PhD.

Drug discovery had historically often relied on trial and error. Hitchings and Elion worked differently: they deliberately designed molecules that would interfere with the production of DNA in cells. Hitchings chose the synthesis of nucleic acids as the target. The idea was to find differences in nucleic acid metabolism between normal human cells and cancer cells, protozoa, bacteria and viruses, and to use them to block the growth of the harmful cells selectively. They found that bacterial cells needed certain purines to make DNA, and reasoned that a compound blocking those purines could stop the cells from growing.

The drugs

Hitchings and Elion synthesized diaminopurine and thioguanine, compounds that proved effective against leukemia. By replacing an oxygen atom with a sulfur atom Elion produced 6-mercaptopurine, which was also used against leukemia. She spent six years studying it and found that treating childhood leukemia with 6-mercaptopurine combined with other drugs was more effective than using it alone.

Other drugs followed from the same approach:

• azathioprine, which suppresses the immune system’s rejection of transplanted organs;
• allopurinol, which reduces the body’s production of uric acid and is used to treat gout;
• pyrimethamine, used against malaria;
• trimethoprim, used against bacterial infections;
• acyclovir, an antiviral used against herpes. It was first synthesized by Howard Schaeffer, and Elion established how it works.

Acyclovir acts on the herpesvirus selectively, and Elion’s colleagues built on that principle to develop AZT for AIDS.

Recognition

Elion became head of the company’s department of experimental therapy in 1967 and held the post until she retired in 1983. In 1970 the laboratory moved to Research Triangle Park, North Carolina, and she moved with it. After retiring she stayed on at the company as scientist emeritus and consultant and became a research professor of medicine and pharmacology at Duke University.

In 1988 she shared the Nobel Prize in Physiology or Medicine with George Hitchings and James Black for their discoveries of important principles for drug treatment. In 1991 she received the National Medal of Science and became the first woman inducted into the National Inventors Hall of Fame. She died in Chapel Hill, North Carolina, on 21 February 1999.