Smithies, Oliver (1925-2017), a British-born American biologist, won the 2007 Nobel Prize in physiology or medicine for his contribution to a technique used to modify genes in mice. Genes direct the formation, growth, and reproduction of living cells and organisms. Smithies shared the prize with the Italian-born American biologist Mario R. Capecchi and the British geneticist Sir Martin John Evans. The three scientists developed methods used to produce knockout mice, strains of laboratory mice in which a particular gene has been inactivated or “knocked out.” Scientists use knockout mice as models for studying gene function and disease.
In the 1980’s, working independently, Smithies and Capecchi studied a process called homologous recombination. Homologous recombination occurs between or within chromosomes, the structures in cells that carry genes. These genes are encoded in the structure of a chainlike molecule called DNA (deoxyribonucleic acid). Homologous recombination occurs when similar chromosomes exchange homologous (corresponding) stretches of DNA, including any genes encoded within them.
Smithies attempted to utilize homologous recombination in gene therapy, the treatment or prevention of disease by altering a patient’s genes. He reasoned that if he could induce recombination between a cell’s chromosomes and artificially injected DNA, he could transfer new DNA onto the chromosome. In this way, he could insert a properly functioning gene into a patient’s cells to repair or replace a defective gene causing a disease. Smithies tried to develop this type of gene therapy to treat inherited blood diseases. In doing so, he discovered that any gene in a cell, whether normal or defective, could be inactivated through homologous recombination. Capecchi reached a similar conclusion.
Smithies and Capecchi’s work enabled scientists to knock out genes within individual mammalian cells. Around the same time, Evans developed the additional methods that later enabled Smithies and other scientists to produce entire knockout mice. Scientists could then observe the effect of the targeted gene by comparing the development of the knockout mice with that of mice with the active gene. Knockout mice have been used to study the role of various genes in development and in human diseases, such as cystic fibrosis, diabetes, and hypertension.
Smithies was born in Halifax, England, on June 23, 1925. He studied biochemistry at Oxford University, where he received his doctorate in 1951. He held faculty positions at the University of Toronto in Canada from 1953 to 1960, at the University of Wisconsin at Madison from 1960 to 1988, and at the University of North Carolina in Chapel Hill from 1988 until his death. He became a United States citizen in 1969. Smithies died on Jan. 10, 2017.
See also Capecchi, Mario Renato ; Evans, Sir Martin John .
