Early Life and Academic Foundations in Japan and U.S.
Born in Nagoya, Japan, on September 5th, 1939, the son of an engineer, Susumu Tonegawa was the first Japanese scientist to win the Nobel Prize for Medicine in 1987. As the second of three sons in a family that also included a younger sister, his early life was shaped by frequent relocations to rural southern Japan due to his father’s work in textile factories. These countryside settings nurtured his natural curiosity and love for exploration. When the children reached adolescence, the family sent the boys to Tokyo to access better educational opportunities.
Tonegawa became interested in chemistry while studying at the prestigious Hibiya High School, which he commuted to from his uncle’s home in Tokyo. After graduating, he chose to take the entrance examination for the Department of Chemistry at Kyoto University and after one unsuccessful attempt, was admitted in 1959 — a year before the renewal of the Japan–U.S. defence treaty that stirred national unrest. Though not actively involved in politics, the tense atmosphere influenced his decision to move away from chemical engineering and pursue an academic path instead.
Tonegawa began his studies in molecular biology under Professor Itaru Watanabe at the Institute of Virus Research at Kyoto University, but after two months, Watanabe, acknowledging the limitations of Japan’s molecular biology programs, including his own—urged Tonegawa to pursue graduate studies in the U.S. and offered to support his applications. Taking this advice and with the support of Watanabe and Dr. Takashi Yura, then an assistant professor in Watanabe’s lab, he was admitted to the graduate school of the Department of Biology at the University of California, San Diego.
He published several papers on the genetics of transcription in bacteriophages under Masaki Hayashi in the Department of Biology, University of California. At UCSD, he carried out a thesis project on the transcriptional control of phage lambda and received his Ph.D. in molecular biology in 1968. He then remained in Professor Hayashi’s laboratory as a postdoctoral fellow working on the morphogenesis of phage ØX174 until early 1969. Tonegawa later accepted a postdoctoral fellowship in Renato Dulbecco’s lab at the Salk Institute of Biological Studies in La Jolla.
In Renato Dulbecco’s laboratory, which focused on small tumour viruses like polyoma and SV40, Tonegawa worked on defining SV40 transcripts during lytic infection and in transformed cells. This was a time before restriction enzymes and recombinant DNA, so his research was limited, but he appreciated the lab’s stimulating atmosphere. Due to his Fulbright grant expiring, Tonegawa had to leave the U.S. by the end of 1970. Shortly before his visa expired, Dulbecco suggested Tonegawa explore immunology at the newly established Basel Institute for Immunology in Switzerland, despite his limited knowledge of the field.
A Breakthrough in Immunology: The Nobel-Winning Discovery
On Renato’s advice, he went to work with Niels Jerne, Director of the Basel Institute of Immunology, in Switzerland in January 1971. He quickly immersed himself in immunology, beginning the experiments that led to his Nobel Prize just three years later in the field. “The genetic side of antibody research was a mystery when Tonegawa started his work,” said Bengt Samuelsson, President of Karolinska Institute, which announced that Tonegawa had been awarded the Nobel. “He was the only player in the field between 1976-1978. His work was therefore truly original.”
His work recognized that the diversity of antibodies was a consequence of the huge numbers of lymphocytes present in the body, each with its own combination of functional antibody-producing genes. He showed that the antibody diversity resulted from the process of somatic recombination. Such a process takes place during the development of β lymphocytes in the bone marrow. During this process, the immunoglobulin genes rearrange themselves at random, thus generating billions of different antibodies. His work also rewarded a genetic regulatory element, known as an enhancer. This discovery contributed to our current understanding of cancer-forming mechanisms, notably in the case of blood cancers. Burkitt’s Lymphoma, for example, is caused by the action of an enhancer sequence belonging to an immunoglobulin gene.
Recruited by Professor Salvador E. Luria Director of the Cancer Centre, he returned to the USA in 1981 as a professor at the Centre for Cancer Research at MIT, where he began exploring new directions in immunology. His research focused on antibody gene activation and T cell receptors, leading to the discovery of a transcriptional enhancer and the gamma delta T cell receptor, hinting at a novel arm of immunity. He was a Howard Hughes Medical Institute (HHMI) investigator from 1988 to 2009.
From Immunology to Neuroscience: The Frontier of Memory and Consciousness
In 1994, Tonegawa founded the Centre for Learning and Memory at MIT, now known as the Picower Institute for Learning & Memory. He was the director of RIKEN-MIT Brain Science Institute in Japan from 2009. Tonegawa was an early adopter of optogenetics and biotechnology in neuroscience research, leading to groundbreaking work identifying and manipulating memory engram cells. By turning his attention to neurobiology, his research resulted in the development of drugs for neurological and psychological disorders, including schizophrenia and dementia.
Besides the Nobel, Tonegawa won numerous awards during his lifetime, on being the Albert Lasker Basic Medical Research Award in 1987, for demonstrating that the DNA responsible for antibody production is routinely reshuffled to create new genes during the lifetime of an individual.
Tonegawa is now a freelance science writer and resides in Boston with his wife and two children. He is a fan of the Boston Red Sox and threw out an opening pitch during their 2004 World Series Championship Season.