Smithies wins Nobel Prize for gene targeting discoveries
Dr. Oliver Smithies, Excellence Professor of Pathology and Laboratory Medicine at the University of North Carolina at Chapel Hill School of Medicine, is a co-recipient of this year’s Nobel Prize in physiology or medicine.
The Nobel Foundation announced Oct. 8 that Smithies, along with Mario R. Capecchi of the University of Utah’s Howard Hughes Medical Institute and Sir Martin J. Evans of the United Kingdom, share this year’s Nobel Prize “for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells.”
Smithies received the call from Stockholm at his home in Chapel Hill at 5 a.m. “I now have a peaceful sense of the rounding off of a scientific life,” Smithies said.
The achievement marks the pinnacle of a scientific career for Smithies, a UNC faculty member for 19 years, containing numerous honors and two major innovations that have fundamentally changed the science of genetic medicine and laid the foundation for today’s research into gene therapy. Smithies is the first full-time UNC faculty member to win a Nobel Prize.
In the mid-1980s, while at the University of Wisconsin at Madison, Smithies co-discovered a technique to introduce DNA material in cells, replicated a natural process called homologous DNA recombination. He thought that genetic disorders could be treated by correcting mutations in bone marrow cells, or stem cells. This “gene targeting” led to the creation of transgenic mice, or “designer mice,” that replicated human disease. Smithies’ lab produced the first animal model of cystic fibrosis, a disease caused by one defective gene, and also studied high blood pressure, atherosclerosis and other diseases.
This method also enabled scientists to study specific genes by creating “knock-out mice.” By targeting and removing, or knocking out, a specific gene, researchers can find out what happens when it’s missing. Smithies has used the analogy of removing a steering wheel from a car; without it you soon find out why it has a steering wheel. Now this research method is commonplace in biomedical research and has been the basis for thousands of published papers. According to the Nobel committee, “gene targeting in mice has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come.”
In the 1950s, while at Connaught Medical Research Laboratory in Toronto, Smithies greatly improved gel electrophoresis, a process of separating proteins to identify genes, using starch. The innovation simplified the procedure and became standard in laboratories.
“Oliver Smithies’ innovations have revolutionized genetic research and advanced the effective treatment of many diseases, and millions of people worldwide have better and longer lives because of the talent and determination he has brought to his work,” said Chancellor James Moeser. “For decades, he has embodied the very best of academic research and humanity through his modesty, good humor, creativity and love of invention. Through his example, hundreds of students and colleagues have learned how to help the world through research.
“We are honored to have him as an anchor for the UNC community and grateful that his many contributions have been recognized with a Nobel Prize.”
“Scientist, scholar, mentor – Oliver Smithies adds Nobel Laureate to a long and glorious career,” said Dr. William L. Roper, dean of the UNC School of Medicine, vice chancellor for medical affairs and chief executive officer of the UNC Health Care System. “It gives us great pleasure to say congratulations on achieving this wonderful honor.”
Born in 1925 in Yorkshire, England, Smithies as a young child was drawn to the idea of invention and enjoyed building telescopes and radios. He attended a high school for bright students and won a scholarship to Oxford University. He earned a bachelor of arts degree (first- class honors) in physiology from Oxford in 1946, and he went on to earn his master's degree and doctorate in biochemistry from Oxford in 1951.
In an interview with the Lasker Foundation, which honored him in 2001, Smithies credited his inspiration for science to a comic strip he read as a boy. The strip had an inventor, and, Smithies said, that’s what he wanted to be, and that’s what he always has been.
He also said scientists should have three things in their lives: their work, a hobby and a family. Smithies is married to UNC colleague Dr. Nobuyo Maeda, Robert H. Wagner distinguished professor of pathology and laboratory medicine. He also is a licensed airplane pilot and is especially fond of gliding.
Smithies came to UNC in 1988. His lab focuses on developing animal models for studying gene therapy in hypertension and other genetic disorders, including sickle cell disease. He is a member of UNC’s Lineberger Comprehensive Cancer Center.
Three adjunct faculty members have won the Nobel in physiology or medicine during their appointments at UNC: Martin Rodbell in 1994 and Gertrude B. Elion and George H. Hitchings in 1988. Rodbell worked at National Institute of Environmental Health Sciences. Elion and Hitchings worked at Burroughs Research Laboratories. Rudolph Marcus, a UNC faculty member from 1951 to 1952, won the 1992 prize in chemistry. Peter Agre, a UNC postdoctoral fellow in hematology/oncology from 1978 to 1981, won the 2003 prize in chemistry. Robert F. Furchgott, a 1937 graduate of UNC, won the Nobel for physiology or medicine in 1998.
For the Nobel Prize announcement and a graphic about the work behind the prize, visit: http://nobelprize.org/nobel_prizes/medicine/laureates/2007/
For more about Smithies’ research, visit: http://www.pathology.unc.edu/common/smithies.htm
For more information about UNC ties to the Nobel, visit: http://www.unc.edu/news/archives/oct07/ties100807.html