Susumu Tonegawa

was a Japanese scientist who was the sole recipient of the Nobel Prize for Physiology or Medicine in 1987 for his discovery of V(D)J recombination, the genetic mechanism which produces antibody diversity. Although he won the Nobel Prize for his work in immunology, Tonegawa was a molecular biologist by training and, following his Nobel Prize win, changed fields to neuroscience, examining the molecular, cellular and neuronal basis of memory formation and retrieval.

Early life and education Tonegawa was born in Nagoya, Japan, and attended Hibiya High School in Tokyo. While a student at Kyoto University, Tonegawa became fascinated with operon theory after reading papers by François Jacob and Jacques Monod, whom he credits in part with inspiring his interest in molecular biology. Tonegawa graduated from Kyoto University in 1963 and, due to limited options for molecular biology study in Japan at the time, moved to the University of California, San Diego, to do his doctorate study under Dr. Masaki Hayashi. With encouragement from Dr. Dulbecco, Tonegawa moved to the Basel Institute for Immunology in Basel, Switzerland, in 1971, where he transitioned from molecular biology into immunology studies and carried out his landmark immunology studies. This process is known as V(D)J recombination.

In 1983, Tonegawa also discovered a transcriptional enhancer element associated with antibody gene complex, the first cellular enhancer element.

Neuroscience Shortly following his Nobel Prize, Tonegawa again changed fields from immunology to neuroscience, where he focused his research in the ensuing years.

Tonegawa was an early adopter of optogenetics and biotechnology in neuroscience research, leading to his groundbreaking work identifying and manipulating memory engram cells. In 2012, his lab demonstrated that the activation of a specific sub-population of mouse hippocampal neurons, labelled during a fear conditioning paradigm, is sufficient to evoke a behavioral response correlated with a precise memory trace. This demonstrated for the first time that memory information is stored in specific cellular ensembles in the hippocampus, now frequently called memory engram cells.

More recently, his lab continues to employ optogenetic technology and virus injection techniques to expand their findings on the engram cell ensemble. Notably, Tonegawa uncovered the role of memory engram cell ensembles in memory valence, social memory, as well as their role in brain disorders such as depression, amnesia, and Alzheimer's disease. These works provide proofs of concept for future medical treatments in humans through the manipulation of memory engram ensembles.

Personal life and death Tonegawa resided in the Boston area with his wife, Mayumi Yoshinari Tonegawa, who worked as an NHK (Japan Broadcasting Corporation) director/interviewer and is now a freelance science writer. The Tonegawas have three children, Hidde Tonegawa, Hanna Tonegawa, and Satto Tonegawa (deceased).

He was a fan of the Boston Red Sox, and threw out an opening pitch during their 2004 World Series championship season.

Tonegawa died at his home in San Mateo, California, on July 11, 2026, at the age of 86.

Selected awards and honors 1982 – Louisa Gross Horwitz Prize 1983 – Gairdner Foundation International Award

1984 – Foreign Associate, American Academy of Arts and Sciences of the United States 1986 – Foreign Associate, National Academy of Sciences of the United States 1986 – Robert Koch Prize 1987 – Albert Lasker Award for Basic Medical Research 1987 – Nobel Prize for Physiology or Medicine 1995 – honored on a stamp (Scott No. 1635c) issued by Gambia 2004 – Honorary Degree, Kyoto University 2006 – Elected Fellow, American Association for the Advancement of Science 2007 – RIKEN Fellow 2009 – Honorary Degree, City University of Hong Kong 2010 – David M. Bonner Lifetime Achievement Award, UCSD

Selected publications List of publications by Susumu Tonegawa Tonegawa, S. (1983). Somatic generation of antibody diversity. Nature, 302(5909), 575-581. Gillies, S. D., Morrison, S. L., Oi, V. T., & Tonegawa, S. (1983). A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell, 33(3), 717-728. Mombaerts, P., Iacomini, J., Johnson, R. S., Herrup, K., Tonegawa, S., & Papaioannou, V. E. (1992). RAG-1-deficient mice have no mature B and T lymphocytes. Cell, 68(5), 869-877. Silva, A. J., Stevens, C. F., Tonegawa, S., & Wang, Y. (1992). Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science, 257(5067), 201-206. Haas, W., Pereira, P., & Tonegawa, S. (1993). Gamma/delta cells. Annual review of immunology, 11(1), 637-685.

Poss, K. D., & Tonegawa, S. (1997). Reduced stress defense in heme oxygenase 1-deficient cells. Proceedings of the National Academy of Sciences, 94(20), 10925-10930. Shen, J., Bronson, R. T., Chen, D. F., Xia, W., Selkoe, D. J., & Tonegawa, S. (1997). Skeletal and CNS defects in Presenilin-1-deficient mice. Cell, 89(4), 629-639. Nakazawa, K., Quirk, M. C., Chitwood, R. A., Watanabe, M., Yeckel, M. F., Sun, L. D., Kato, A., Carr, C.A., Johnston, D., Wilson, M.A., & Tonegawa, S. (2002). Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science, 297(5579), 211-218. Liu, X., Ramirez, S., Pang, P. T., Puryear, C. B., Govindarajan, A., Deisseroth, K., & Tonegawa, S. (2012). Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature, 484(7394), 381-385. Ramirez, S., Liu, X., Lin, P. A., Suh, J., Pignatelli, M., Redondo, R. L., Ryan, T.J., & Tonegawa, S. (2013). Creating a false memory in the hippocampus. Science, 341(6144), 387-391.