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1987, “for his discovery of the genetic principle for generation of antibody diversity.”
1987, “for brilliantly demonstrating that the DNA responsible for antibody production is routinely reshuffled to create new genes during the lifetime of an individual.” Click here for more details.
Susumu Tonegawa, Ph.D., AAI '80, Massachusetts Institute of Technology (MIT), was awarded the 1987 Nobel Prize in Physiology or Medicine for "his discovery of the genetic principle for generation of antibody diversity." At a time when the question of how a limited number of genes could produce such a vast array of antibodies perplexed immunologists, Tonegawa demonstrated that antibody diversity was a result of the rearrangement of genes in somatic cells. His findings have allowed for advancements in the areas of vaccination, organ transplantation, and the treatment of autoimmune diseases.1
In a series of experiments conducted between 1974 and 1976,2 Tonegawa sought to determine whether an individual inherited millions of immunoglobulin genes, each responsible for producing a distinct polypeptide chain in a specific antibody, or whether the immune system rearranged genetic information during B cell development, enabling a small number of genes to produce a much larger number of antibodies. Using newly discovered restriction enzymes to fragment DNA, he compared by hybridization the DNA of embryonic mouse cells and adult myeloma cells. Upon discovering that the immunoglobulin genes of adults were arranged differently from their arrangement in the embryonic cells, he concluded that they had been reshuffled during B cell differentiation, allowing the animal to create a wide range of antibodies. In subsequent work, he confirmed the findings by cloning and sequencing antibody-encoding genes.3
In the early 1990s, Tonegawa turned his attention to neurobiology. He has been particularly interested in the molecular and cellular basis of learning and memory. Using genetically modified mice, he has investigated the roles that specific enzymes, genes, and pathways play in both short-term and long-term memory. This research may aid in the development of drugs to treat neurological and psychological disorders, including schizophrenia and dementia.4
"The genetic side of antibody research was a complete mystery to us all when Tonegawa started his work," said Bengt Samuelsson, president of the Karolinska Institute, when announcing that Tonegawa had been awarded the Nobel. "He was the only player in the field between 1976 and 1978. The work was truly unique."5
Tonegawa was born in Nagoya, Japan, on September 6, 1939. After earning his B.S. in chemistry from Kyoto University in 1963, he began graduate study in molecular biology under Itaru Watanabe at the Institute for Virus Research at Kyoto University. Within two months, Watanabe encouraged him to apply for graduate study in the United States. In August of 1963, Tonegawa left Kyoto for the University of California, San Diego, where he studied phages under Masaki Hayashi in the Department of Biology. He earned his Ph.D. in 1968 and remained in Hayashi's laboratory as a postdoctoral fellow for one year before accepting a postdoctoral fellowship in Renato Dulbecco's laboratory at the Salk Institute for Biological Studies in La Jolla. On Dulbecco's advice, Tonegawa, whose U.S. visa was soon to expire, applied to work at the Basel Institute for Immunology in Switzerland. Although Tonegawa had no experience in immunology, Niels Jerne (AAI '73), the director of the institute, brought him to Switzerland in January of 1971. Tonegawa quickly immersed himself in immunological research, beginning the experiments for which he was awarded the Nobel after only three years in the field.
Recruited by Salvador Luria (AAI '58), Tonegawa returned to the United States in 1981 to accept a professorship at the Center for Cancer Research at MIT. He was a Howard Hughes Medical Institute investigator from 1988 to 2009. After shifting his focus to neuroscience, he founded the Center for Learning and Memory at MIT (now the Picower Institute for Learning and Memory) and has been the director of the RIKEN-MIT Center for Neural Circuit Genetics since 2008 and of the RIKEN Brain Science Institute in Japan since 2009.6
Tonegawa is a member of the American Academy of Arts and Sciences (1984) and a foreign associate of the National Academy of Sciences (1986).
In addition to the Nobel Prize, Tonegawa's honors include the Warren Triennial Prize (1980), the Louisa Gross Horwitz Prize (1982), the Gairdner Foundation International Award (1983), the Robert Koch Prize (1986), the Albert Lasker Basic Medical Research Award (1987), selection as an AAI Distinguished Lecturer (1988), and the David M. Bonner Lifetime Achievement Award (2010).7
1 "Physiology or Medicine 1987—Press Release," Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1987/press.html.
2 S. Tonegawa, C. Steinberg, S. Dube, and A. Bernardini, "Evidence for Somatic Generation of Antibody Diversity," Proceedings of the National Academy of Sciences of the United States of America 71, no. 10 (1974): 4027–31; S. Tonegawa, "Reiteration Frequency of Immunoglobulin Light Chain Genes: Further Evidence for Somatic Generation of Antibody Diversity," Proceedings of the National Academy of Sciences of the United States of America 73, no. 1 (1976): 203–7; N. Hozumi and S. Tonegawa, "Evidence for Somatic Rearrangement of Immunoglobulin Genes Coding for Variable and Constant Regions," Proceedings of the National Academy of Sciences of the United States of America 73, no. 10 (1976): 3628–32.
3 "Albert Lasker Basic Medical Research Award—1987 Award Description," Lasker Foundation, http://www.laskerfoundation.org/awards/1987_b_description.htm#tonegawa; Patricia J. Gearheart, "The Birth of Molecular Immunology," The Journal of Immunology 173, no. 7 (2004): 4259.
4 "Susumu Tonegawa, Ph.D.—HHMI Alumni Scientist," Howard Hughes Medical Institute, http://www.hhmi.org/research/investigators/tonegawa_bio.html.
5 "Susumu Tonegawa—Autobiography," Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1987/tonegawa-autobio.html; "Susumu Tonegawa—Curriculum Vitae," Tonegawa Laboratory, http://www.tonegawalab.org/st/tonegawa-cv.pdf.
6 Susumu Tonegawa—Curriculum Vitae," Tonegawa Laboratory.