Obituary: George Hitchings

GEORGE HITCHINGS was an outstanding discoverer of medicines which have given benefit to sufferers all over the world. He devised Daraprim for malaria and Zyloric for gout, both exceptional remedies which have stood the test of time; but the main application of his work was in cancer chemotherapy.

Hitchings was born in Hoquiam, Washington, in 1905. His family was prominent in shipbuilding, but he decided early to devote his life to a search for new medicines. He studied Biochemistry for bachelor's and master's degrees at the University of Washington, and continued to work for his PhD from Harvard.

In 1942 he joined the American laboratories of the firm of Burroughs Wellcome (now part of Glaxo Wellcome) in Tuckahoe, New York, where he developed the programme of his life work. Scientists in those laboratories had an exceptional and enviable freedom to decide for themselves what to work on and how to work on it. Hitchings, one of the few scientists of the time to recognise the importance of deoxyribonucleic acid or DNA in life processes, chose to study purines and pyrimidines, the building blocks of DNA.

He and his research partner Gertrude Elion exploited the then recently established principle of competitive antagonism and made drugs which would arrest the multiplic- ation of specific cells, either of an invading parasite or of a cancer.

The enormous progress in the next quarter of a century provided the medicines which enabled Burroughs Wellcome to become a major pharmaceutical company. In Hitchings's own words, "The results are cumulative; the solution of one problem creates the tools and understanding that facilitate the solution of the next problem." The first important success was the anti-malarial drug Daraprim or pyrimethamine, which was tested in the Wellcome Institute of Tropical Medicine in London and in the tropics.

This very valuable discovery was, however, a diversion from the primary interest of finding anti-cancer drugs. The compound 6-mercaptopurine was made and found to cause remissions in children with certain types of leukaemia. Very few anti-cancer drugs were known at the time, and the success, although limited, was a great encouragement to Hitchings's and Elion's line of work.

Studies of the metabolic fate of purines suggested an effective treatment for gout. The result was an outstanding success, the drug Zyloric, or allopurinol, remarkably free from unwanted effects, and of undoubted benefit in preventing the very painful attacks of the disease.

While these discoveries were being made and the more basic research which supported them was continuing, the science of immunology was growing fast. The idea that immune responses depended on division of particular cells suggested that anti-cancer drugs might act also as immunosuppressants. Mercaptopurine was found to stop immune responses in rabbits, and further compounds were developed, resulting in the immunosuppressant azathioprine, sometimes described as the drug which made organ transplantation possible.

By this time Hitchings had a world-wide reputation. In 1967 Burroughs Wellcome appointed him as Vice-President of Research. He was then involved in planning new research laboratories for the company's move to Research Triangle Park in North Carolina. Here he led a large and flourishing department in which outstanding chemotherapeutic discoveries continued to be made, including drugs for the treatment of herpes and Aids.

In 1976 he was elected as a Foreign Member of the Royal Society of London; in 1977 he was inducted into the US National Academy of Science; in 1978 he received the Annual Award of the American Cancer Society. In 1988 he and Gertrude Elion shared the Nobel Prize in Medicine with the British pharmacologist Sir James Black.

Hitchings continued to be based in the Wellcome laboratories, and was increasingly involved in philanthropy. He served as President of the Burroughs Wellcome Fund, a private foundation which supported pharmaceutical research, from 1971 to 1989. He founded the Triangle Community Foundation in 1983 and served as its President until 1985. He retired from Burroughs Wellcome as Scientist Emeritus in 1994, shortly before his 90th birthday.

George Hitchings was a quiet but formidable man of great integrity and great kindness. He had a splendid sense of fun which came out delightfully in the right circumstances. With an innate love of plants, he was a most knowledgeable gardener. His silences could be embarrassing, and the concentration of his thought was sometimes overpowering, but what came from it was profoundly worth hearing.

George Herbert Hitchings, chemist: born Hoquiam, Washington 18 April 1905; Teaching Fellow, Washington University 1926-28; Teaching Fellow, Harvard University 1928- 34, Instructor and Tutor 1932-36, Research Fellow 1934-36, Associate 1936- 39; Senior Instructor, Western Reserve University 1939-42; Biochemist, Burroughs Wellcome Co 1942-46, Chief Biochemist 1946-55, Associate Research Director 1955-63, Research Director (Chemotherapy Division) 1963-67, Vice- President in Charge of Research 1967-75, Director 1968-77, Scientist Emeritus and Consultant 1975-98; Professor of Pharmacology, Brown University 1968- 80, Staff, Department of Medicine, Roger Williams General Hospital 1970- 80; Adjunct Professor of Pharmacology and Adjunct Professor of Experimental Medicine, Duke University 1970-85; President, Burroughs Wellcome Fund 1971-90, Director 1971-94; Adjunct Professor of Pharmacology, University of North Carolina at Chapel Hill 1972-85; Nobel Prize in Physiology or Medicine (jointly with Gertrude Elion and Sir James Black) 1988; married 1933 Beverly Reimer (died 1985; one son, one daughter), 1989 Joyce Shaver; died Chapel Hill, North Carolina 27 February 1998.

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