Susumu Tonegawa (利根川 進, Tonegawa Susumu; born September 5, 1939) is a Japanese scientist who was the only person to receive the Nobel Prize for Physiology or Medicine in 1987. He was honored for discovering V(D)J recombination, a genetic process that creates diversity in antibodies. Although he received the Nobel Prize for his research in immunology, Tonegawa was trained as a molecular biologist. After winning the Nobel Prize, he changed fields again and now studies neuroscience. His current work focuses on understanding the molecular, cellular, and neuronal processes involved in forming and retrieving memories.

Early life and education

Tonegawa was born in Nagoya, Japan, and attended Hibiya High School in Tokyo. While studying at Kyoto University, Tonegawa became very interested in operon theory after reading papers by François Jacob and Jacques Monod, whom he credits as part of the reason for his interest in molecular biology. Tonegawa graduated from Kyoto University in 1963. Because there were not many choices for studying molecular biology in Japan at that time, he moved to the University of California, San Diego, to complete his doctoral studies under Dr. Masaki Hayashi. He received his Ph.D. in 1968.

Career

Tonegawa completed postdoctoral research at the Salk Institute in San Diego under the guidance of Dr. Renato Dulbecco. With Dr. Dulbecco's support, Tonegawa moved to the Basel Institute for Immunology in Basel, Switzerland, in 1971. There, he shifted his focus from molecular biology to immunology and conducted important research in this field.

In 1981, Tonegawa became a professor at the Massachusetts Institute of Technology (MIT). In 1994, he was named the first director of the MIT Center for Learning and Memory. Under his leadership, the center became known as The Picower Institute for Learning and Memory. Tonegawa stepped down as director in 2006 and now holds the title of Picower Professor of Neuroscience and Biology at MIT. He also serves as a Howard Hughes Medical Institute Investigator.

From 2009 to 2017, Tonegawa directed the RIKEN Brain Science Institute.

Research

Tonegawa's Nobel Prize research explained how the adaptive immune system works using genes. This was a major question in immunology for over 100 years. Before his discovery, one idea suggested that each gene makes one protein. However, the human body has fewer than 19,000 genes, yet can produce millions of antibodies. Starting in 1976, Tonegawa showed that genetic material rearranges itself to create these antibodies. By comparing DNA in B cells (a type of white blood cell) from embryonic and adult mice, he found that genes in adult B cells move, recombine, and delete to form the diverse parts of antibodies. This process is called V(D)J recombination.

In 1983, Tonegawa discovered a DNA segment that helps control the activity of antibody genes, the first known cellular enhancer element.

After winning the Nobel Prize, Tonegawa shifted his research from immunology to neuroscience, where he has focused his work for many years.

Tonegawa's lab developed early methods to create transgenic and gene-knockout models in mammals. He contributed to early studies showing the role of CaMKII (1992) and NMDA receptor-dependent synaptic plasticity (1996) in forming memories.

His lab found that dendritic spines in the temporal cortex may be a target for treating Fragile X Syndrome. Using the drug FRAX586, he showed a significant reduction in symptoms in a mouse model of the condition.

Tonegawa used optogenetics and biotechnology in neuroscience research, leading to discoveries about memory engram cells. In 2012, his lab showed that activating a specific group of neurons in the mouse hippocampus, labeled during a fear conditioning experiment, caused a behavior linked to a specific memory. This proved that memories are stored in specific groups of neurons in the hippocampus, now called memory engram cells.

Recently, his lab continues using optogenetics and virus injections to study engram cell groups. He has found how these cells are involved in memory valence, social memory, and brain disorders like depression, amnesia, and Alzheimer's disease. These findings suggest possible future treatments for humans by controlling memory engram cells.

Personal life

Tonegawa currently lives in the Boston area with his wife, Mayumi Yoshinari Tonegawa. She previously worked as a director and interviewer for NHK, the Japan Broadcasting Corporation, and now works as a freelance science writer. The Tonegawas have three children: Hidde Tonegawa, Hanna Tonegawa, and Satto Tonegawa, who has passed away. Tonegawa is a fan of the Boston Red Sox and threw out the first pitch during the 2004 World Series championship season.

Selected awards and honors

• 1982 – Received the Louisa Gross Horwitz Prize
• 1983 – Awarded the Gairdner Foundation International Award
• 1984 – Received the Order of Culture (Bunkakunsho) from the Emperor of Japan
• 1984 – Became a Foreign Associate of the American Academy of Arts and Sciences in the United States
• 1986 – Became a Foreign Associate of the National Academy of Sciences in the United States
• 1986 – Received the Robert Koch Prize
• 1987 – Awarded the Albert Lasker Award for Basic Medical Research
• 1987 – Received the Nobel Prize for Physiology or Medicine
• 1995 – Featured on a stamp (Scott No. 1635c) issued by Gambia
• 2004 – Received an Honorary Degree from Kyoto University
• 2006 – Became a Member of the American Association for the Advancement of Science
• 2007 – Named a RIKEN Fellow
• 2009 – Received an Honorary Degree from the City University of Hong Kong
• 2010 – Awarded the David M. Bonner Lifetime Achievement Award by UCSD

Selected publications

• List of publications by Susumu Tonegawa
• Tonegawa, S. (1983). Somatic generation of antibody diversity. Nature, Volume 302, Issue 5909, Pages 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, Volume 33, Issue 3, Pages 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, Volume 68, Issue 5, Pages 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, Volume 257, Issue 5067, Pages 201-206.
• Haas, W., Pereira, P., & Tonegawa, S. (1993). Gamma/delta cells. Annual review of immunology, Volume 11, Issue 1, Pages 637-685.
• Tsien, Joe Z.; Huerta, Patricio T.; Tonegawa, Susumu (1996). "The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory." Cell, Volume 87, Issue 7, Pages 132