Snell, George Davis

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Snell, George Davis

(b. 19 December 1903 in Bradford, Massachusetts; d. 6 June 1996 in Bar Harbor, Maine), immunogeneticist whose pioneering research on the human immune system paved the way for organ transplantation and earned him a Nobel Prize.

Snell was the youngest of three children of Cullen Bryant Snell and Katharine Merrill Davis. His father was secretary of a Young Men’s Christian Association for many years; later, the elder Snell invented and marketed a device for winding induction coils used in motorboat engines. The family moved to suburban Brookline, Massachusetts, when Snell was four, and he and his brother and sister grew up in a home built by his great-grandfather. Snell attended the Brookline public schools and favored science and mathematics. He loved sports and played in his high school band, a reflection of the musical inclination of his entire family.

From 1922 to 1926 Snell attended Dartmouth College in Hanover, New Hampshire, earning a B.S. degree in biology. He then began graduate studies at Harvard University, working with Professor William Castle, one of the first American biologists to research Mendelian inheritance in mammals. Snell completed his M.S. in 1928 and was granted a Ph.D. in 1930. He wrote his doctoral dissertation on linkage in mice (that is, the means by which two or more genes on a chromosome are interrelated).

While completing his doctoral degree at Harvard, from 1929 to 1930, Snell taught zoology at Dartmouth College. The following academic year, Snell taught zoology at Brown University in Providence, Rhode Island. Then, in 1931 he accepted a National Research Council fellowship at the University of Texas at Austin, where he worked with the prominent geneticist Hermann J. Muller. Muller would later win a Nobel Prize for showing that X rays could induce mutations in the common fruit fly. In his own research, Snell demonstrated for the first time that mice subjected to X rays often exhibited chromosomal damage.

From 1933 to 1934 Snell was an assistant professor at Washington University in St. Louis, but his time in Austin had convinced him that research was his true calling. In 1935 he accepted a position as a research associate at the Roscoe B. Jackson Memorial Laboratory in Bar Harbor, Maine. The Jackson Laboratory, founded by the geneticist Clarence Cook Little, was a center for study on mammalian genetics and renowned for its program on mouse genetics. At first, Snell continued his research with X rays and mice. Later, he helped develop a standardized gene nomenclature for mice. Then, in the early 1940s he shifted his attention to transplantation genetics.

Scientists knew that certain genes controlled the body’s acceptance or rejection of tissue transplants, but the precise genes had not been isolated or identified. Snell set out to find these “histocompatibility” genes, as he called them. In a complicated procedure, he took two inbred lines of laboratory mice that did not accept grafts from each other and repeatedly crossbred them. After many generations, he had two strains of mice that were genetically identical except for the genes that controlled transplant rejection. Snell called the genes he had isolated the “his to compatibility locus.” The mice Snell had bred, which he called “congenic,” had made it possible to follow the effects of a single gene in a constant genetic background. Snell’s breeding of these so-called congenic mice was a new and important contribution to genetics research.

In 1946 Peter Gorer of Guy’s Hospital in London, England, joined Snell in his research at the Jackson Laboratory. Years earlier, Gorer had identified a blood protein, which he named Antigen-II, that was related to graft rejection in mice. Snell and Gorer quickly discovered that Snell’s his to compatibility locus and Gorer’s Antigen-II were one and the same and combined their nomenclature to call the gene His to compatibility Two, or H-2. By the mid-1950s Snell identified a group of about ten loci that actually control transplant resistance. The H-2 locus was, in reality, a group of closely linked genes. These genes would become known as the major his to compatibility complex, or MHC.

In the late 1950s scientists discovered that humans also possess a major his to compatibility complex. The immunogeneticist Jean Dausset identified the first human his to compatibility protein and hypothesized correctly that there was a single set of MHC genes in humans that corresponded to the H-2 system in the mouse. In 1969 Baruj Benacerraf found that genes within the MHC determine whether or not the body can produce an immunological response to a foreign substance. He and other scientists determined, in the mid-1970s, that MHC products help white blood cells distinguish normal body cells from abnormal or foreign cells. In 1980 the Nobel Prize for physiology or medicine was awarded jointly to Snell, Dausset, and Benacerraf “for their discoveries concerning genetically determined structures on the cell surface that regulate immunologic reactions.” Their work was a chronological sequence over several decades, and Snell’s contribution was discovering “the genetic factors that determine the possibilities of transplanting tissues from one individual to another.”

Snell’s career at the Jackson Laboratory spanned nearly forty years. His later research focused on the role the MHC plays in relation to tumor resistance and cancer. He retired in 1973, having achieved the rank of senior staff scientist emeritus. Even after retirement, Snell frequently visited the lab. He also spent time writing on science, philosophy, and ethics.

In addition to the Nobel Prize, Snell’s many awards included the Bertner Foundation Award (1962), the Gregor Mendel Medal of the Czechoslovakian Academy of Sciences (1967), the Gairdner Foundation International Award (1976), and the Wolf Prize in medicine (1978). He was a member of the American Academy of Arts and Sciences, the National Academy of Sciences, and the Transplantation Society. Snell wrote Search for a Rational Ethic (1988) and coauthored Histocompatibility (1976) with Dausset and Stanley Nathenson. Snell was also editor of The Biology of the Laboratory Mouse (1941) and from 1947 until 1980 was editor of the journal Immunogenetics.

On 28 July 1937 Snell married Rhoda Carson. The couple had three sons, Thomas, Roy, and Peter. Snell was a physically slight man, with reserved blue eyes behind thin-rimmed glasses. His personality was described as modest and shy. At work, Snell was diligent, precise, and patient. At home, he enjoyed his vegetable garden and tended it with the same exacting care as he did his work. Snell lived out his years in Bar Harbor, where he had spent most of his adult life as a quintessential New Englander.

Snell’s pioneering research earned him the unofficial title “father of modern immunogenetics.” Because of his work, doctors can predict compatibility in human organ transplants, giving hope to many where there was none before.

Articles about Snell and his work include “3 Cell Researchers Win Medicine Nobel,” New York Times (11 Oct. 1980); “1980 Nobel Prize in Physiology or Medicine,” Science (7 Nov. 1980); and “Portrait: Dr. George D. Snell: The Maine Hunter in White Coat,” Life (Feb. 1981). Biographical sketches appear in Nobel Prize Winners (1987) and Contemporary Authors, vol. 106 (1982). An obituary is in the New York Times (8 June 1996).

Victoria Tamborrino