Oliver Smithies

  PhotoOliver Smithies was born on June 23, 1925, in Halifax. He was a student at Heath Grammar School in Halifax until he was awarded a scholarship from Balliol College, Oxford University. At Oxford, he received a Bachelor of Arts Degree in Physiology with First Class Honors in 1946. In 1951, he obtained his M.A. and D.Phil. degrees in Biochemistry from Oxford. Smithies then moved to the United States as a Postdoctoral Fellow in Physical Chemistry at the University of Wisconsin. After two years at Wisconsin, Smithies accepted a position at the Connaught Medical Research Laboratories in Toronto. In 1960, Smithies returned to Wisconsin as Assistant Professor of Medical Genetics and Genetics, advancing to Full Professor by 1963. He was named the Leon J. Cole Professor in 1971. In 1988, he joined the Department of Pathology at the University of North Carolina, as the Excellence Professor of Pathology. He is now the Weatherspoon Eminent Distinguished Professor of Pathology and Laboratory Medicine at UNC, and remains an actively engaged scientist working in the laboratory. In the 1950s, Smithies described the first high resolution electrophoresis system (starch gel), and with it he discovered that normal humans have unsuspected inherited differences in their proteins. His technique of starch-gel electrophoresis opened vast areas of new study. Its descendant (polyacrylamide gel electrophoresis) is a vital everyday tool of all molecular biologists. With this technique, Smithies uncovered protein polymorphisms in normal persons and worked on the heredity of several blood proteins – including haptoglobins, transferrins, and gamma globulins. This work was recognized by an award from the Gairdner Foundation. In 1985, Smithies described his second ground-breaking technique – the use of homologous recombination to alter a human gene in a living cell. Subsequent application of homologous recombination by Smithies, and independently by Capecchi, combined with the work of Sir Martin Evans on embryonic stem cells, led to the now world-wide use of gene targeting to “knock out” genes, study their function, and to generate mouse models of human genetic diseases. This work was recognized by a second Gairdner Foundation award (with Capecchi), and by the Nobel Prize (with Capecchi and Evans). With this technique Smithies has determined how genes affect blood pressure in healthy persons, and how the same genes influence the kidney problems that affect some but not all persons with diabetes.