As the end of 1970 approached in La Jolla, California, Japanese molecular biologist Susumu Tonegawa faced a rigid administrative deadline. His United States visa, tied to a Fulbright travel grant, was expiring, mandating a strict two-year departure from the country. Tonegawa, born in Nagoya in 1939, had earned his Ph.D. at the University of California, San Diego in 1968 under Masaki Hayashi. He was then working as a postdoctoral fellow in Renato Dulbecco’s laboratory at the Salk Institute, mapping transcripts of the tumor virus SV40. The imminent visa expiration threatened to halt his research momentum entirely.
A Relocation to Switzerland
According to the Nobel Prize biographical account, Tonegawa had few compelling research options outside the United States. In the autumn of 1970, he received a letter from Dulbecco, who was traveling in Europe. Dulbecco suggested that a molecular biologist could apply modern genetic tools to unsolved problems in immunology at the newly founded Basel Institute for Immunology in Switzerland. Tonegawa followed the advice and submitted an application to the institute's director, Niels Kaj Jerne. Jerne offered Tonegawa a two-year contract, and Tonegawa relocated to Basel in the winter of 1971. Initially unfamiliar with immunology, Tonegawa spent his first year learning the field, aided by geneticist Charles Steinberg and immunologist Ita Askonas.
Mapping Somatic Recombination in Basel
By late 1971, Tonegawa had turned his focus to the long-standing debate over how the immune system generates millions of distinct antibodies from a limited set of inherited genes. Applying restriction enzymes and recombinant DNA techniques—tools previously unused in immunology—he built a research group that initially included technicians Monica Shöld and Rita Schuller, and later expanded to include researchers Nobumichi Hozumi, Minoru Hirama, and Christine Brack, alongside Steinberg. Between 1974 and 1981 at the Basel Institute, Tonegawa's group compared the genetic structure of immunoglobulin genes in embryonic cells against mature antibody-producing cells. Their experiments demonstrated that antibody diversity is not fully pre-encoded in inherited DNA, but is generated through somatic recombination—the physical shuffling and rearrangement of inherited gene segments—as well as somatic mutation during cell maturation.
Return to America and Molecular Discoveries
With the mechanism of antibody diversity established, Tonegawa returned to the United States in 1981 to accept a professorship at the Massachusetts Institute of Technology's Center for Cancer Research under Director Salvador E. Luria. At MIT, Tonegawa expanded his research into cellular immunity. His laboratory identified a tissue-specific transcriptional enhancer within the immunoglobulin heavy chain gene, explaining how rearranged antibody genes are selectively activated. Additionally, while cloning T cell receptor subunits, Tonegawa's team identified a distinct gene subunit that led to the discovery of the gamma delta T cell receptor. For his discoveries regarding the genetic principles of antibody diversity, Tonegawa was awarded the Albert and Mary Lasker Award and the Nobel Prize in Physiology or Medicine in 1987.
The Molecular Logic of Immune Adaptability
Tonegawa’s enforced departure from California ultimately altered the course of immunology. By proving that somatic recombination allows a compact set of inherited gene segments to assemble into millions of distinct antibodies, his work demonstrated the precise molecular mechanism by which higher organisms construct an adaptable immune defense from a limited genetic blueprint.
Cover: AI-generated editorial illustration; not a documentary photograph.
Source: Nobel Prize
Susumu Tonegawa
SIGNAL TITANS
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