Oliver Smithies (23 June 1925 – 10 January 2017) was a British-American scientist who studied genes and how living things work at a very small level. In 1955, he introduced starch as a material used in a method called gel electrophoresis, which helps separate molecules. He also worked with Mario Capecchi and Martin Evans to develop a technique called homologous recombination, which allows new DNA to be inserted into an organism's existing DNA. This method is more reliable than older ways of changing animal genes and is the basis for creating knockout mice, which are important in genetic research. In 2007, he was awarded the Nobel Prize in Physiology or Medicine for his work in genetics.
Early life and education
Smithies was born in Halifax, West Yorkshire, England, to William Smithies and his wife, Doris, whose maiden name was Sykes. His father sold life insurance policies, and his mother taught English at Halifax Technical College. He had a twin brother and a younger sister. He attended primary school in the nearby village of Copley and later went to Heath Grammar School in Halifax. He said his interest in science began when he was young and loved radios and telescopes.
He attended Balliol College, Oxford, on a Brackenbury Scholarship, initially studying medicine. He studied body structure and how the body works, winning a prize in anatomy. He graduated with a first-class Bachelor of Arts degree in animal physiology, including biochemistry, in 1946. Inspired by lessons from Alexander G. Ogston on using chemistry to study living things, Smithies changed his focus and earned a second bachelor's degree in chemistry. He published his first research paper, co-written with Ogston, in 1948. In 1951, he received a Master of Arts degree and a Doctor of Philosophy in biochemistry under Ogston's guidance; his thesis was titled "Physico-chemical properties of solutions of proteins."
Career
Smithies received a Commonwealth Fund fellowship to begin a job after his doctorate in the United States, working in the laboratory of J. W. Williams at the University of Wisconsin–Madison's Department of Chemistry. A problem getting a U.S. visa, because of a rule from the fellowship, made him leave the U.S. From 1953 to 1960, he worked as an assistant research scientist, under insulin researcher David A. Scott, at the Connaught Medical Research Laboratory at the University of Toronto in Canada. He studied medical genetics with Norma Ford Walker at the Hospital for Sick Children in Toronto.
In 1960, Smithies returned to the University of Wisconsin–Madison, where he worked in the Department of Genetics until 1988. He held positions as assistant, associate, and Leon J. Cole and Hilldale Professor of Genetics and Medical Genetics. Later, he became the Excellence Professor of Pathology and Laboratory Medicine at the University of North Carolina at Chapel Hill. He continued working in his lab there every day until his eighties. He co-authored more than 350 research papers and reviews from 1948 to 2016.
Research
Smithies created the gel electrophoresis technique using a starch matrix while working at the University of Toronto. This research was part of a study on an insulin precursor molecule that did not lead directly to major results. His method improved the ability to separate proteins using electrophoresis. Otto Hiller helped him with technical aspects of his later electrophoresis experiments. Smithies used starch electrophoresis to identify differences in normal human plasma proteins. With Norma Ford Walker, he showed that these differences were inherited, which increased his interest in genetics.
At the University of Wisconsin in the 1980s, Smithies developed gene targeting in mice, a method that replaces individual mouse genes using homologous recombination. Mario Capecchi also discovered this technique independently. This research became the foundation for global studies on how specific genes contribute to human diseases such as cancer, cystic fibrosis, and diabetes. In 2002, Smithies worked with his wife, Nobuyo Maeda, to study high blood pressure in genetically altered mice.
Awards and honors
Smithies won the 2001 Albert Lasker Award for Basic Medical Research, along with Martin Evans (Cardiff University) and Mario Capecchi (University of Utah), for their work on homologous recombination. He shared the Wolf Prize in Medicine with Capecchi and Ralph L. Brinster in 2002 or 2003. He received the 2007 Nobel Prize in Physiology or Medicine, along with Capecchi and Evans, "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells."
Other awards he received include two Gairdner Foundation International Awards (1990 and 1993), the North Carolina Award for Science (1993), the Alfred P. Sloan, Jr. Prize from the General Motors Foundation, shared with Capecchi (1994), the Ciba Award from the American Heart Foundation (1996), the Bristol Myers Squibb Award (1997), the Association of American Medical Colleges' Award for Distinguished Research, shared with Capecchi (1998), the International Okamoto Award from the Japan Vascular Disease Research Foundation (2000), the O. Max Gardner Award, the highest award for faculty in the University of North Carolina system (2002), the Massry Prize of the Meira and Shaul G. Massry Foundation (2002), shared with Capecchi, the March of Dimes Prize in Developmental Biology, shared with Capecchi (2005), and the American Institute of Chemists Gold Medal (2009).
Smithies was elected to the United States National Academy of Sciences (1971), the American Academy of Arts and Sciences (1978), the American Association for the Advancement of Science (1986), the Institute of Medicine (2003), and as a foreign member of the Royal Society (1998). He received honorary degrees from the University of Chicago (1991), the University of São Paulo (2008), and the University of Oxford (2011).
A blue plaque was placed in his honor by the Halifax Civic Trust.
Personal life
Smithies married Lois Kitze, a virologist at the University of Wisconsin, in the 1950s; they separated in 1978. His second wife, Nobuyo Maeda, is a pathology professor at the University of North Carolina. Smithies became a U.S. citizen and, even though he was color-blind, was a licensed pilot who enjoyed gliding. He called himself an atheist. Smithies died on January 10, 2017, at the age of 91.