Susumu Tonegawa, who died on July 11 at the age of 86, won the Nobel Prize in Physiology or Medicine for solving one of the great puzzles of immunology, then spent the next three decades doing the same for memory. The two halves of his career look like a single scientific method applied twice. Asked how he had managed to transform two fields, he gave an answer that was less about himself than about how he chose problems: scientists should ask how an emerging technology might offer a fresh approach to a really big question. Antibody diversity was the first question, and the new technology was molecular biology itself, the restriction enzymes and DNA cloning methods that let him read and rearrange genes. Memory was the second, and the new technology was genetic manipulation of the mouse brain. Both bets paid off, and in doing so they changed what it meant to be a molecular biologist.
The immunology problem was a century old. The human genome contains roughly 25,000 genes, yet the immune system can produce antibodies against what seems like an infinite variety of foreign molecules. How could so few genes encode so many antibodies? In 1976, working at the Basel Institute for Immunology with Nobumichi Hozumi, Tonegawa showed that antibody genes are not fixed. In B cells, the white blood cells that produce antibodies, the DNA itself is rearranged: segments of the genes for antibody chains are cut out and rejoined in new combinations, generating billions of different antibodies from a small set of building blocks. The discovery, now known as V(D)J recombination, explained how a limited genome could encode an unbounded immune repertoire. It also carried a deeper lesson. Combined with Barbara McClintock’s work on maize, it demonstrated that genome stability is not sacrosanct, that genomes contain movable elements whose rearrangement can profoundly shape physiology. For that work Tonegawa received the 1987 Nobel Prize, as the sole laureate, becoming the first Japanese scientist to win the prize in physiology or medicine.
His path to Basel had been indirect. Born in Nagoya in 1939, he studied chemistry at Kyoto University, then moved to the United States for a PhD in molecular genetics at the University of California, San Diego, working on gene regulation in lambda phage, and did postdoctoral research at the Salk Institute under Renato Dulbecco. It was Dulbecco who steered him toward immunology, then a field that seemed ripe for the application of molecular biology, and who pointed him to the newly founded Basel Institute for Immunology when his US visa was about to expire. At the time Tonegawa knew little immunology; he has said he never understood why scientists studied antibodies themselves rather than the genes that encode them, an instinct that turned out to be exactly right.
In 1981 he moved to MIT, where he remained for more than four decades. The turn to neuroscience came when he decided the immune system’s mysteries were largely spent and memory was the bigger question. He founded MIT’s Center for Learning and Memory, later renamed the Picower Institute, and built a laboratory that brought the tools of molecular genetics, including cell-type-specific gene knockouts such as the CAMKII mutants his group created, to bear on the brain. The centerpiece came in 2013, when his team identified engrams, the physical traces of memory, in the hippocampus and showed that a specific memory is stored in a specific group of cells. In the same year they implanted false memories in mice, reactivating an engram with optogenetics while the animal formed a new memory so that it came to associate a location with an event that had happened elsewhere; the work was named one of the top ten scientific breakthroughs of 2014 by Science magazine. Later studies showed that engrams are not confined to the hippocampus but distributed across many connected brain regions, and his final projects probed the engrams of abstract knowledge and how the brain marks time.
His influence extended beyond his own results. He served as director of the RIKEN Brain Science Institute in Japan, headed the RIKEN-MIT Center for Neural Circuit Genetics, and was an investigator of the Howard Hughes Medical Institute. Colleagues remember an intellectual giant who was shy in daily life but never shy in science, a fierce competitor who loved results that ran against conventional wisdom. His honors included the Lasker Award, the Gairdner International Award, the Robert Koch Award, and Japan’s Order of Culture.
Tonegawa’s two careers are often told as a story of range, a man who happened to master two fields. The sharper reading is that he applied one discipline twice: find the biggest unsolved question, then find the newest tool that could approach it fresh. The method worked in immunology because molecular biology was ready to be pointed at antibody genes. It worked in neuroscience because genetics was ready to be pointed at memory. That the same man recognized both moments, thirty years apart, is what made him a fearless molecular biologist who revealed the workings of antibodies and memories, his former postdoctoral fellow Adrian Hayday wrote in his Nature obituary.
References
Adrian Hayday, Obituary: Susumu Tonegawa, Japan’s first Nobel prizewinner in physiology or medicine. Nature 656, 31 (2026). DOI: 10.1038/d41586-026-02340-8.
Anne Trafton, MIT Professor Susumu Tonegawa, renowned molecular biologist and Nobel laureate, dies at 86. MIT News, 15 July 2026.
Susumu Tonegawa, first Japanese Nobel laureate in medicine, dies at 86. The Japan Times, 16 July 2026.