Oliver Smithies of the University of North Carolina at Chapel Hill was awarded the 2007 Nobel Prize in Physiology or Medicine for pioneering homologous recombination of transgenic DNA, which allowed for the creation of knockout and transgenic mice. Smithies’ lab created the first murine models of cystic fibrosis. He has also identified genetic factors involved in heart disease, atherosclerosis, and other disorders. In an interview with JCI Editor-at-large Ushma Neill, Dr. Smithies discusses his early interest in science, including his propensity for tinkering, the invention of starch gel electrophoresis, and his first molecular genetic studies of haptoglobin. Smithies also describes the three year development of his protocol for genetic transformation of human cells, his feelings on winning the Nobel Prize, and his admiration for Johann Sebastian Bach.