Sakaguchi Traveled Rocky Road in Research Leading to Nobel Prize

Tokyo, Oct. 7 (Jiji Press)–Japan’s Shimon Sakaguchi, who has been named this year’s winner of the Nobel Prize in Physiology or Medicine, did not always enjoy smooth sailing during his research life dedicated to the human immune system that led to the discovery of regulatory T cells. Sakaguchi, 74, had been viewed as a maverick researcher because his research centered on suppressing immune responses while many other researchers sought ways to strengthen the immune system. Despite going in the opposite direction from the mainstream, Sakaguchi continued his research and opened the way for new therapies that suppress excessive immune reactions. A native of Shiga Prefecture, western Japan, Sakaguchi, professor at the University of Osaka, grew up in an easy-going environment, enjoying reading various kinds of books from his childhood. After studying at Shiga Prefectural Nagahamakita High School, he advanced to Kyoto University’s Faculty of Medicine, where he became interested in diseases involving the immune system. The immune system normally attacks viruses and other foreign substances that enter the body, but attacks itself in autoimmune diseases such as rheumatoid arthritis. “There’s a philosophical appeal to the issue of how the immune system distinguishes between itself and others,” Sakaguchi says. When Sakaguchi was a graduate student, he became interested in a research article released by a group from the Aichi Cancer Center in Aichi Prefecture, central Japan, which found that mice whose thymuses were removed developed diseases resembling autoimmune disorders. Sakaguchi dropped out of his graduate school, which he had found boring, and joined the Aichi Cancer Center as a research student. This meant that he stepped off the mainstream track for researchers. Sakaguchi said in a paper he published in 1982 that some normal lymphocytes suppress immune reactions. In 1985, he was convinced of the existence of regulatory T cells, which modulate the immune system. However, the main theme of immunology research at the time was to find ways to create immune responses, which was exactly opposite to Sakaguchi’s theme. But Sakaguchi patiently carried on his research on suppressing immune reactions although the research field gradually lost popularity after entering the spotlight in the second half of the 1970s. Sakaguchi moved to the United States and conducted research for about 10 years. He then came back to Japan, but did not return to his alma mater and instead continued his research at a different institution. In 1995, he discovered a regulatory T cell marker. While his research began to gain understanding little by little, an important molecule of regulatory T cells has been found in 2003. Today, Sakaguchi’s work is highly recognized as research leading to the development of new therapies for not only autoimmune disorders but also cancer. One immunologist said that Sakaguchi spent an unfortunate research life for a long period of time, with his work underrated and unrecognized by the world. “An ordinary researcher would have given up and quit.” But Sakaguchi laughs that off. “I have a lot of nerve,” he says. “I didn’t think I was unfortunate.” In the world of research, prevailing theories and views tend to change with time. Sakaguchi says he has always gone back to the starting point of his research and made a fresh start every time the general trend changed. His advice to young researchers is this: “It is important to keep up your interest in what you want to know.” The Nobel Assembly at the Karolinska Institute in Sweden announced Monday that it has decided to award this year’s Nobel Prize in Physiology or Medicine to Sakaguchi and two U.S. researchers–Mary Brunkow of the Institute for Systems Biology of the United States and Fred Ramsdell of U.S. biotechnology company Sonoma Biotherapeutics–for their discoveries of regulatory T cells. END [Copyright The Jiji Press, Ltd.]