is a Japanese scientist who was the sole recipient of the

Nobel Prize for Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...

in 1987 for his discovery of

V(D)J recombination V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell rece ...

, the genetic mechanism which produces

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

diversity. Although he won the Nobel Prize for his work in

immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...

, Tonegawa is a

molecular biologist Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

by training and he again changed fields following his Nobel Prize win; he now studies

neuroscience Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...

, examining the molecular, cellular and neuronal basis of memory formation and retrieval.

Early life and education

Tonegawa was born in

Nagoya is the largest city in the Chūbu region, the fourth-most populous city and third most populous urban area in Japan, with a population of 2.3million in 2020. Located on the Pacific coast in central Honshu, it is the capital and the most pop ...

, Japan and attended

Hibiya High School is a Japanese high school founded in 1878 as the . It was well known in the 1950s and 1960s for the large proportion of graduates who gained admission to the prestigious University of Tokyo; though it suffered a decline in the 1970s, as of 2005 ...

in Tokyo. While a student at

Kyoto University , mottoeng = Freedom of academic culture , established = , type = National university, Public (National) , endowment = ¥ 316 billion (2.4 1000000000 (number), billion USD) , faculty = 3,480 (Teaching Staff) , administrative_staff ...

, Tonegawa became fascinated with

operon theory In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

after reading papers by

François Jacob François Jacob (17 June 1920 – 19 April 2013) was a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through regulation of transcription. He shared the 1965 Nobel Prize i ...

and

Jacques Monod Jacques Lucien Monod (February 9, 1910 – May 31, 1976) was a French biochemist who won the Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and André Lwoff "for their discoveries concerning genetic control of en ...

, whom he credits in part for 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 The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...

to do his doctorate study under Dr. Masaki Hayashi. He received his Ph.D. in 1968.

Career

Tonegawa conducted post-doctoral work at the

Salk Institute The Salk Institute for Biological Studies is a scientific research institute located in the La Jolla community of San Diego, California, U.S. The independent, non-profit institute was founded in 1960 by Jonas Salk, the developer of the polio vacci ...

San Diego San Diego ( , ; ) is a city on the Pacific Ocean coast of Southern California located immediately adjacent to the Mexico–United States border. With a 2020 population of 1,386,932, it is the List of United States cities by population, eigh ...

in the laboratory of

Renato Dulbecco Renato Dulbecco ( , ; February 22, 1914 – February 19, 2012) was an Italian–American virologist who won the 1975 Nobel Prize in Physiology or Medicine for his work on oncoviruses, which are viruses that can cause cancer when they infect anima ...

. With encouragement from Dr. Dulbecco, Tonegawa moved to the

Basel Institute for Immunology The Basel Institute for Immunology (BII) was founded in 1969 as a basic research institute in immunology located at 487 Grenzacherstrasse, Basel, Switzerland on the Rhine River down the street from the main Hoffmann-La Roche campus near the Swiss-G ...

in Basel, Switzerland in 1971, where he transitioned from molecular biology into immunology studies and carried out his landmark immunology studies. In 1981, Tonegawa became a professor at the Massachusetts Institute of Technology. In 1994, he was appointed as the first Director of the MIT Center for Learning and Memory, which developed under his guidance into The

Picower Institute for Learning and Memory The Picower Institute for Learning and Memory is, along with the McGovern Institute for Brain Research and the Department of Brain and Cognitive Sciences, one of the three neuroscience groups at MIT. The institute is focused on studying all aspect ...

. Tonegawa resigned his directorship in 2006 and currently serves as a Picower Professor of Neuroscience and Biology and a

Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization based in Chevy Chase, Maryland. It was founded in 1953 by Howard Hughes, an American business magnate, investor, record-setting pilot, engineer, fil ...

Investigator. Tonegawa also served as Director of the

RIKEN Brain Science Institute RIKEN Brain Science Institute (RIKEN-BSI) was established in 1997 as part of RIKEN, focusing on neuroscience research located in Wakō city, Saitama Prefecture in the greater Tokyo area, Japan. In 2018 RIKEN-BSI has been reorganized as RIKEN Ce ...

from 2009 to 2017.

Research

Immunology

Tonegawa's Nobel Prize work elucidated the genetic mechanism of the adaptive immune system, which had been the central question of immunology for over 100 years. Prior to Tonegawa's discovery, one early idea to explain the adaptive immune system suggested that each gene produces one protein; however, there are under 19,000 genes in the human body which nonetheless can produce millions of antibodies. In experiments beginning in 1976, Tonegawa showed that genetic material rearranges itself to form millions of antibodies. Comparing the DNA of

B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

(a type of

white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...

) in embryonic and adult

mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

, he observed that genes in the mature B cells of the adult mice are moved around, recombined, and deleted to form the diversity of the variable region of antibodies. This process is known as

. 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 in 1990, Tonegawa again changed fields from immunology to neuroscience, where he has focused his research in the ensuing years. Tonegawa's lab pioneered introductory transgenic and gene-knockout technologies in mammalian systems. He was involved in early work demonstrating the importance of CaMKII- (1992) and the NMDA receptor-dependent synaptic plasticity (1996) in memory formation. Tonegawa's lab discovered that dendritic neuronal spines in the temporal cortex are a likely target for treatment of Fragile X Syndrome. With one dosage of the inhibitor drug FRAX586, Tonegawa showed a marked reduction of FXS symptoms in the mouse model. Tonegawa was an early adopter of

optogenetics Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individu ...

and

biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...

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 has 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

Tonegawa currently resides in the Boston area with his wife, Mayumi Yoshinari Tonegawa, who worked as an

NHK , also known as NHK, is a Japanese public broadcaster. NHK, which has always been known by this romanized initialism in Japanese, is a statutory corporation funded by viewers' payments of a television license fee. NHK operates two terrestri ...

(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). Tonegawa is a fan of the Boston Red Sox, and threw out an opening pitch during their 2004 World Series championship season.

Selected awards and honors

*1982 –

Louisa Gross Horwitz Prize The Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers who have made an outstanding contribution in basic research in the fields of biology or biochemist ...

*1983 –

Gairdner Foundation International Award The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a p ...

*1984 –

Order of Culture The is a Japanese order, established on February 11, 1937. The order has one class only, and may be awarded to men and women for contributions to Japan's art, literature, science, technology, or anything related to culture in general; recipien ...

(Bunkakunsho), Emperor of Japan *1984 – Foreign Associate,

American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and ...

of the United States *1986 – Foreign Associate,

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...

of the United States *1986 –

Robert Koch Prize The Robert Koch Medal and Award are two prizes awarded annually by the German for excellence in the biomedical sciences. These awards grew out of early attempts by German physician Robert Koch to generate funding to support his research into the ...

*1987 –

Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...

*1987 –

*1995 – honored on a stamp (Scott No. 1635c) issued by

Gambia The Gambia,, ff, Gammbi, ar, غامبيا officially the Republic of The Gambia, is a country in West Africa. It is the smallest country within mainland AfricaHoare, Ben. (2002) ''The Kingfisher A-Z Encyclopedia'', Kingfisher Publicatio ...

*2004 – Honorary Degree,

*2006 – Member,

American Association for the Advancement of Science The American Association for the Advancement of Science (AAAS) is an American international non-profit organization with the stated goals of promoting cooperation among scientists, defending scientific freedom, encouraging scientific respons ...

*2007 – RIKEN Fellow *2009 – Honorary Degree,

City University of Hong Kong City University of Hong Kong (CityU) is a world-class public research university located in Kowloon Tong, Hong Kong. It was founded in 1984 as City Polytechnic of Hong Kong and became a fully accredited university in 1994. Currently, CityU is ...

Honorary Doctor of Science Professor Susumu TONEGAWA
/ref> *2010 – David M. Bonner Lifetime Achievement Award, UCSD

Selected publications

List of publications by Susumu Tonegawa
* Tonegawa, S. (1983). Somatic generation of antibody diversity

* 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

* 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

References

External links

Faculty Webpage at MIT Biology
* ttp://www.cumc.columbia.edu/horwitz/ The Official Site of Louisa Gross Horwitz Prizebr>www.tonegawalab.orgSusumu Tonegawa
on The Picower Institute * {{DEFAULTSORT:Tonegawa, Susumu 1939 births Foreign associates of the National Academy of Sciences Living people Japanese immunologists Japanese molecular biologists Japanese neuroscientists Nobel laureates in Physiology or Medicine Japanese Nobel laureates Recipients of the Order of Culture Kyoto University alumni Members of the European Molecular Biology Organization Massachusetts Institute of Technology School of Science faculty People from Nagoya University of California, San Diego alumni Recipients of the Albert Lasker Award for Basic Medical Research Scripps Research Howard Hughes Medical Investigators Riken personnel