British-born American scientist who, with Mario R. Capecchi (Capecchi, Mario R.) and Sir Martin J. Evans (Evans, Sir Martin J.), won the 2007 Nobel Prize for Physiology or Medicine for developing gene targeting, a technology used to create animal models of human diseases in mice.

In 1951 Smithies earned both a master's degree and a doctorate in biochemistry from the University of Oxford and later moved to the United States, where he studied at the University of Wisconsin. In 1988 he joined the faculty at the University of North Carolina in Chapel Hill.

While researching gene therapy as a method for treating hereditary diseases, Smithies uncovered the work that Evans had been doing on the embryonic stem cells of mice. Using a sample obtained from Evans, he demonstrated that targeted removal or alteration of genes within the stem cells allowed for the controlled manipulation of the mouse genome. In 1991 Smithies created a “knockout mouse”—so named because one of its genes had been experimentally replaced or “knocked out”—that accurately modeled human cystic fibrosis.