Obituary of Oliver Smithies

By Jane Stancill jstancill@newsobserver.com Oliver Smithies, a UNC-Chapel Hill professor and Nobel Prize winner, died Tuesday at UNC hospitals after a short illness. He was 91. Smithies was a pioneer in the field of gene targeting and "knockout mice," which are used to study how specific genes worked. He created the first animal model of cystic fibrosis in 1992, and his technique of creating designer mice advanced the understanding of many diseases, including cancer, obesity and heart disease. His work was at the foundation of the field of gene therapy. He received the Nobel Prize in physiology or medicine in 2007 for his development of a technique called homologous recombination that introduced targeted genetic modifications to cells. Smithies shared the prize with Mario Capecchi of the University of Utah's Howard Hughes Medical Institute and Sir Martin Evans of the United Kingdom. He was a beloved figure at UNC, where he practically lived in his lab when he wasn't flying his glider over Chapel Hill. He worked alongside his wife, Nobuyo Maeda, a professor of pathology and laboratory medicine at UNC's School of Medicine. They joined the UNC faculty in 1988. "Oliver Smithies was such a loving, wonderful force for all things good in this world," Chancellor Carol Folt said in a statement. "Spending time with Oliver and Nobuyo has been one of the highlights of my tenure at Carolina. Every time I saw the two of them together, I was uplifted and inspired by their relationship, joyful attitude to life and generosity of spirit." UNC colleagues mourned his passing and celebrated his many achievements - he had received many of the world's top awards in science. Oliver was a truly remarkable person with a joy for life and science. His brilliance was paired with infectious enthusiasm that inspired everyone around him. Dr. J. Charles Jennette, chairman of UNC-Chapel Hill's department of pathology and laboratory medicine "Oliver was a truly remarkable person with a joy for life and science. His brilliance was paired with infectious enthusiasm that inspired everyone around him," said Dr. J. Charles Jennette, chairman of the department of pathology and laboratory medicine. On that day in 2007, his lab threw together a party for the modest, British-born scientist. In his cluttered office, little toy mice lined his bookshelves. "I feel rather peaceful," he said then. "I've been working at the bench for more than 50 years, and it's nice to find that people appreciate what you've done. It feels like what a lot of people have mentioned - a capstone on one's career." He said he got a "nice little glow" whenever he would open a scientific journal and see that scientists the world over were using his methods. The work of isolating genes was tedious and he sometimes had to build his own tools. In describing the process that he and his fellow laureates used, Smithies evoked an easy-to-understand analogy. "Imagine a book with a thousand pages, and each page has a thousand letters, and now you have a library with a thousand of these books," he told The News & Observer in 2007. "What the three of us devised was a way to say, 'Well, that thing you've got in volume 230, I'm interested in Page 96, and at the bottom of Page 96 there's this word, I don't understand what it means. Change it and see what happens.' And that's what we found we could do." Smithies and his fraternal twin brother were born on June 23, 1925, in Halifax, England. A bout with rheumatic fever at age 7 kept him out of sports activities, so he turned to books. In 1943, he received a scholarship to Oxford University, where he studied medicine before changing the concentration of his studies to physiology. He received his bachelor's degree in physiology in 1946, and went on to earn his master's degree and doctorate in biochemistry from Oxford in 1951. Smithies did postdoctoral work at the University of Wisconsin before joining the Connaught Medical Research Laboratory in Toronto, where he worked from 1952 until 1960. It was here that Smithies developed his starch gel electrophoresis technique. The high-resolution gels that Smithies created allowed researchers to study blood proteins effectively. Before this, scientists thought that blood plasma contained five different proteins. Smithies found 25 proteins. He returned to the University of Wisconsin in 1960, where he was one of the first scientists to physically separate a gene from the rest of the DNA of the human genome. Two decades later, he would jot down an experimental plan to modify specific genes. His experiments in gene engineering would transform the work in his lab and labs everywhere. By isolating genes, scientists could find new treatments. Last fall, UNC launched the Oliver Smithies Research Archive website to make available to the world the 150-plus notebooks where Smithies recorded his notes daily. Smithies began the habit as a graduate student at Oxford. When he received his Nobel at age 82, Smithies said the idea of retirement hadn't entered his mind. "I've always said if I were to die somewhere, which certainly will happen, it might as well be at the bench because that's where I'm happy." Plans for a memorial service are pending.