Susumu Tonegawa, a pioneering molecular biologist whose groundbreaking discoveries transformed immunology and neuroscience, died on July 11 at his home in San Mateo, California. He was 86. The Massachusetts Institute of Technology (MIT), where he served as a professor, confirmed his passing.
Dr. Tonegawa received the Nobel Prize in Physiology or Medicine in 1987 for uncovering the mechanism by which the human body produces a vast array of antibodies to combat diverse infections. His later work focused on understanding how memories are formed and stored in the brain, advancing the field of neuroscience.
For many years, scientists struggled to explain how antibodies—Y-shaped proteins produced by B lymphocytes that neutralize pathogens—could generate sufficient diversity to recognize millions of different antigens. While portions of the antibodies’ protein chains remain constant, the variable segments allow the immune system to target countless threats. Researchers debated whether this diversity was encoded in the genome inherited across generations or if it was generated within the body after birth through gene modification in somatic cells.
In 1974, while working at the Basel Institute for Immunology in Switzerland, Dr. Tonegawa employed innovative molecular techniques to investigate this conundrum. By comparing DNA sequences from mouse embryonic tissue and myeloma cancer cells using hybrid probes of messenger RNA, he demonstrated that antibody diversity results from somatic recombination—dynamic rearrangements and alterations of gene segments occurring in immune cells. This finding decisively showed that the body rearranges DNA to create new antibodies, resolving a long-standing scientific debate.
Dr. Tonegawa published these landmark findings in 1976 and continued to develop his research, earning the Nobel Prize for revealing the genetic basis of antibody diversity. The Nobel committee noted the implications of his work for vaccine development, immunotherapies, and treatments for autoimmune diseases.
In 1994, after joining MIT, Dr. Tonegawa shifted his focus to neuroscience. He established the MIT Center for Learning and Memory, now known as the Picower Institute for Learning and Memory, where he studied how memories are encoded in the brain. Using advanced technologies, he identified specific groups of cells called engrams in the hippocampus—key to processing new memories—and showed that these cells integrate various aspects of experience, such as space, time, and sensory input, to form distinct memories. His experiments in mice demonstrated the ability to manipulate these engram cells to create or alter memories.
Researchers at MIT have highlighted the potential therapeutic applications of his memory work, including treatments for conditions like post-traumatic stress disorder and neurodegenerative diseases such as Alzheimer’s, through modulation or suppression of harmful memories.
Born on September 5, 1939, in Nagoya, Japan, Dr. Tonegawa was the son of Tsutomu and Miyoko Tonegawa. He held various roles in the family’s engineering and textiles business before pursuing his scientific career. He joined the Basel Institute in 1971 and was recruited to MIT in 1981 by Nobel laureate Salvador E. Luria. Dr. Tonegawa is survived by his wife, Mayumi Yoshinari, whom he married in 1985, and two children, Hidde and Hanna. A third child, Satto, passed away in 2011.