George H. Hitchings Biography (1905-1998)


George H. Hitchings was among the most prolific of modern pharmaceutical scientists. He worked at Burroughs Wellcome Company, a British pharmaceutical company with research facilities in the United States, for more than thirty years before his retirement in 1975. Hitchings produced many important pharmaceuticals for treating diseases such as cancer, gout, and malaria, and for preventing rejection of transplanted organs. His contributionswere based on the premise that an understanding of what makes diseased cellsdifferent from normal cells makes it possible to exploit those differences to destroy cancer cells or foreign invaders such as bacteria or viruses with drugs. For his work in finding treatments for serious diseases, Hitchings andhis long-time Burroughs Wellcome collaborator Gertrude Elion shared the 1988 Nobel Prize in physiology or medicine with British pharmaceutical scientist Sir James Black. It was the first time since 1957 that pharmaceutical scientists had been awarded the prize.

George Herbert Hitchings was born to George Herbert Hitchings, Sr., a naval architect, and Lillian H. Belle Hitchings on April 18, 1905, in Hoquiam, Washington, on the Olympic Peninsula. His father's death when he was twelve and his admiration for Louis Pasteur , a preeminent scientist-philanthropistwho became his role model, aimed Hitchings toward a career in medicine. As the salutatorian of his high school class, Hitchings gave an address to the graduating class on the germ theory and Pasteur's life.

Hitchings attended the University of Washington, where he received a bachelor's degree in chemistry in 1927 and a master's degree in chemistry in 1928. Healso showed a fondness for many scholarly subjects, studying the arts and history in college. He began his career in scientific research at an early age."The Chemistry of the Waters of Argyle Lagoon," the first of his more than three hundred scientific publications, appeared in the publications of the Puget Sound Biological Station in 1928, when he had just entered graduate school. He continued his graduate work in biological chemistry at Harvard College,where he received his Ph.D. in 1933. Hitchings' doctoral dissertation concerned the metabolism of nucleic acids, the chemicals that make up DNA, the carrier of genetic information. Hitchings did his work on nucleic acids before James Watson and Francis Crick discovered the structure ofDNA, and at that time no one was interested in nucleic acids. Hitchings couldn't find a job. Finally, after working for nine years as a teaching fellow atHarvard (1933-39) and Western Reserve University (1939-42), he was hired byBurroughs Wellcome in 1942 and resumed his work on nucleic acids. He became vice president of research in 1967 and held the position until 1975, when he became scientist emeritus.

Until Hitchings and the pharmacologist Gertrude Elion came along, drug researchers sought new drugs by modifying natural products. The two pioneered a method that has come to be known as "rational" drug design . They reasoned thatif they understood the differences between normal and diseased or infected cells, these differences could serve as a entry point to selectively kill diseased tissue without harming surrounding normal tissue. They implemented theseideas by investigating the chemical pathways of nucleic acid synthesis, whichis crucial to cell metabolism. Hitchings synthesized chemicals similar in structure to natural nucleic acids, the purines and pyrimidines. These relatedcompounds interfered with DNA synthesis. Because cancer cells divide quickly,the compounds are particularly disruptive to them, killing them as they tryto divide. This form of chemotherapy is just one instance of the rational drug design that helped Hitchings accumulate eighty-five patents over histhirty-year career.

One compound in particular, 6-mercaptopurine (6MP), a purine analog synthesized in 1951, proved to be particularly effective. Working with scientists at Sloan-Kettering Institute, Hitchings and Elion perfected the drug, which was used to combat childhood leukemia . 6MP and thioguanine, also producedby Hitchings and Elion, are still used to treat acute leukemias.

In 1959 Hitchings discovered that 6MP inhibited production of antibodies in rabbits. A less toxic form called azathioprine, marketed under the trade nameImuran, was developed in 1957 to control rejection of transplanted organs andtreat autoimmune diseases. In the nearly nine thousand kidney transplants performed each year, Imuran remains the drug most commonly used to prevent organ rejection. 6MP is broken down in the body by xanthine oxydase, the same enzyme that converts purines into uric acid, the cause of the painful joint disease gout. Further investigation of purine analogs led to the development of allopurinol in the 1960s. It blocks uric acid production by competing for xanthine oxydase, an enzyme that converts purines to uric acid. Hitchings was also active in the development of other drugs, including pyrimethamine , which is used to treat malaria, and trimethoprim , which is used to treat urinary tract infections and other bacterial infections.

Philanthropy had always been a part of Hitchings' life, and he has said thatwhen he was baptized his father dedicated his life to the service of mankind.He served as president of the Burroughs Wellcome fund, a charitable organization, from 1971 to 1990. In addition, he has served as director of a dozen local chapters of philanthropic organizations.

Hitchings married Beverly Reimer in 1933. The couple had two children, Laramie Ruth and Thomas Eldridge. Beverly died in 1985. In 1989, Hitchings was remarried to Joyce Shaver. He died on February 27, 1998 in Chapel hill, North Carolina.

Besides the Nobel Prize, Hitchings received numerous awards, including the Gregor Mendel Medal from the Czechoslovakian Academy of Science in 1968 and theAlbert Schweitzer International Prize for Medicine in 1989. He was awarded eleven honorary degrees and was a member of the National Academy of Sciences.In addition, he traveled widely, lecturing in Africa, Asia, Europe and SouthAmerica.

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