Sunday, April 18, 2010

George Herbert Hitchings


George Herbert Hitchings was born on April 18, 1905 in Hoquiam, Washington, the son of George Herbert Hitchings, shipbuilder and Lilian Matthews Hitchings. Although not well educated, his parents were avid readers and their thirst for knowledge was passed on to him. Hitching's father died when he was only twelve. Due to his family's wanderings Hitchings attended grade school Berkeley and San Diego, California and Bellingham, Washington. He completed his secondary education in Seattle, Washington, where he was class salutatorian.

In 1923 he entered the University of Washington and initially intending to be a pre-medical student, however the enthusiasm of the students and faculty of the chemistry department shifted his course to become a chemistry student. He finished his B.S. in 1927 and is M.S. in 1928. He then went to Harvard University, where he was assigned to work with Cyrus Fiske, whose group was studying analytical methods for studying purines and had detected and isolated adenosine triphosphate (for a brief review of purine chemistry see here). Hitchings finished his Ph.D. in 1933 and for the next nine years served in a variety of temporary positions including doing cancer research at the C. P. Huntington Laboratories at Harvard, doing nutrition research at the Harvard School of Public Health, and doing electrolyte research at Western Reserve University Medical School.

In 1942 Hitchings joined Burroughs Wellcome Research Laboratories (now GlaxoSmithKline), in Tuckahoe, New York as the head and sole member of the biochemistry department. At first his resources were limited and this allowed him to be free to develop his own methods of inquiry. In 1944 he hired Gertrude Elion as a laboratory assistant, beginning a life-long collaboration in drug research. They began investigating the way that purines and pyrimidines are synthesized and metabolized by human cells, bacteria and viruses. Inspired by the recent development of sulfa drugs, they began investigating other substances that could inhibit microbial growth by mimicking these nitrogen containing bases. Their research indicated that bacteria could not synthesize nucleic acids without the presence of certain purines in their growth media and this led them to investigate substances that would inhibit the incorporation of purines into their DNA.

DNA (and RNA) is made up of three components: nitrogen containing bases, deoxyribose (a five carbon sugar missing an oxygen on carbon 2, that in RNA is replaced by ribose) and phosphate. There are two different types of nitrogen containing bases which make up the part of the DNA that carries the information used to synthesize proteins: purines, which have a bicyclic structure composed of a six membered ring fused to a five membered ring, and pyrimidines which contain a six membered ring. adenine and guanine are the purines, and cytosine and thiamine are the pyrimidines that are found in DNA. The focus of Hitchings' research was to find a chemical analog of one of these bases which would inhibit the microbial enzymes which were responsible for synthesizing it's DNA. These nitrogen containing base analogs can also be used to inhibit the growth of cancer cells, which require them for their rapid growth.

In 1947 Hitchings began to receive financial assistance from the Sloan-Kettering Institute in exchange for providing compounds to be used in cancer treatment. Among the compounds that they developed for the treatment of cancer are diaminopurine, thioguanine and 6-mercaptopurine, which have all been used in the treatment of leukemia due to their ability to block the synthesis of DNA in white blood cells. They also developed azathioprine, a less toxic form of 6-mercaptopurine, which can be used to block the immune reaction after organ transplants and allopurinol, a drug used to treat gout by blocking the synthesis of uric acid, an end product of purine metabolism. Hitchings and Elion also developed zidovudine, which led directly to the development of AZT, one of the first drugs used to treat A.I.D.S.

In 1967 Hitchings became the vice president of research for Burroughs Wellcome and he retired and became a scientist emeritus in 1976. In 1968 he became director and in 1971 president of the Burroughs Wellcome Fund, a charitable foundation dedicated to funding medical research. He also served as director and vice president of The United Way and director and chairman of the American Red Cross. In 1988 he and Gertrude Elion (along with Sir James Black) were awarded the Nobel Prize for Physiology or Medicine. Other honors he received include the Gregor Mendel Medal from the Czechoslovakian Academy of Science in 1968 and the Albert Schweitzer International Prize for Medicine in 1989. He was awarded 11 honorary degrees and was made a member of the National Academy of Science.

Hitchings died on February 27, 1998.


References:

Harvey, Robert C.; "Hitchings, George H." in American National Biography: Supplement 2 (American National Biography Supplement)
; Mark C. Carnes, Editor; Oxford University Press, 2005

Hitchings, George H., Nobel Prize Autobiography at nobelprize.org

Kresge, Nicole, Simoni, Robert D., and Hill, Robert L.; "The Rational Design of Nucleic Acid Inhibitors to Treat Leukemia: The Work of George H. Hitchings"; The Journal of Biological Chemistry (2008) 283: e10


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