The Nobel Prize in Physiology or Medicine 1987

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Susumu Tonegawa

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Susumu Tonegawa

Born: 6 September 1939, Nagoya, Japan

Affiliation at the time of the award: Massachusetts Institute of Technology (MIT), Cambridge, MA, USA

Prize motivation: "for his discovery of the genetic principle for generation of antibody diversity"

Autobiography

I was born in Nagoya, Japan on September 6th, 1939, the second of three sons. I have also a younger sister. My father was an engineer working for a textile company that had several factories scattered in rural towns in the southern part of Japan. The company policy made it necessary for my father to move from one factory to another every few years. I and my brothers and sister spent most of our childhood in these small provincial towns, enjoying the space and freedom of the countryside. As my elder brother and I reached adolescence, however, my parents decided to send us to Tokyo so that we could receive a better education.

I commuted to the prestigious Hibiya high school from my Uncle's home in Tokyo. During the high school years I developed an interest in chemistry, so upon graduation, I chose to take an entrance examination for the Department of Chemistry of the University of Kyoto, the old capital of Japan. After having failed once, I was admitted to this University in 1959. This happened to be one year before the first ten-year term of the defence treaty between Japan and the United States expired and the governments of both countries were preparing for a second ten-year term.

The nation was deeply divided between the pragmatic pro-American conservatives and the idealistic anti-military leftists. Being the home of the most radical leftist student groups, classes at Kyoto University were often cancelled due to frequent political discussions and demonstrations on the streets. I was only a passive participant, withdrawn from the turmoil, but could not help having a feeling of defeat shared with many of my classmates when the treaty was finally extended for the next ten-year term. I believe that this experience might have been a major factor in making me give up the original goal of becoming a chemical engineer to pursue the academic life.

I became fascinated by the then blossoming science of molecular biology when in my senior year I happened to read the papers by François Jacob and Jacques Monod on the operon theory. I decided to pursue graduate study in molecular biology and was accepted by Professor Itaru Watanabe's laboratory at the Institute for Virus Research at the University of Kyoto, one of a few laboratories in Japan where U.S.-trained molecular biologists were actively engaged in research. However, only two months after I started my work in his laboratory, Professor Watanabe called me into his office and suggested that I carry out my graduate study in the United States. He explained how inadequate the graduate training programs in molecular biology laboratories were in Japan, including his own, and offered to help in my application to some major universities in the United States, if I would seriously consider studying abroad.

At that time, it was a common career development for a Japanese molecular biologist to go to the United States for a few years of postdoctoral study after obtaining the Ph.D. in Japan. I already had a vague wish to follow that pattern. Professor Watanabe's advice to enroll in an American graduate school therefore came to me as a bit of a surprise, but I was excited by the idea and accepted his help immediately. I cannot thank Professor Watanabe enough for this critical suggestion in the early phase of my scientific career.

With the additional help of Dr. Takashi Yura, then an assistant professor in Watanabe's laboratory, I was admitted to the graduate school of the Department of Biology of the University of California at San Diego that had recently been established by Professor David Bonner in La Jolla, the beautiful southern Californian town near the Mexican border.

At UCSD I studied in the laboratory of Professor Masaki Hayashi, carrying out a thesis project on the transcriptional control of phage lambda and received my Ph.D. in molecular biology in 1968. I remained in Professor Hayashi's laboratory as a postdoctoral fellow working on the morphogenesis of a phage, ØX174, until early 1969. Then I moved, also as a postdoctoral fellow, across the street to the laboratory of Dr. Renato Dulbecco at the Salk Institute.

Like many others, I believed that the golden age of prokaryotic molecular biology was coming to an end and that the great excitement would be in higher organisms. However, the complexity of high organisms was baffling and the necessary tools seemed hopelessly insufficient. Small tumor viruses like polyoma and simian virus 40, the biological material primarily dealt with in Dulbecco's laboratory, seemed to offer a bridge for the gap between prokaryotes and eukaryotes. Indeed Dulbecco's laboratory was filled with first-class postdoctoral fellows from around the world, who were trained in prokaryotic molecular biology and who came there intending to expand their research into eukaryotic molecular biology.

My project was to define the transcripts of SV40 during lytic infection and in transformed cells. Since this was the pre-restriction enzyme and pre-recombinant DNA age, the information I could obtain was very limited. However, being a member of the best laboratory in the field I glimpsed the excitement of the cutting edge of scientific research. Furthermore, I very much enjoyed the free and stimulating atmosphere of the laboratory. Unfortunately, as an awardee of a Fulbright travel grant, my U.S. visa was to expire by the end of 1970 and I had to leave the country for at least two years before I was eligible for another U.S. visa.

I had two or three job possibilities outside of the United States, but none were particularly interesting. In the autumn of 1970, only a few months before my visa was to expire I received a letter from Renato Dulbecco who was travelling in Europe. Renato mentioned the newly established Basel Institute for Immunology in Basel, Switzerland, and suggested that the time might be ripe for a molecular biologist to tackle immunological problems. I had very little knowledge of immunology, but decided to take Dr. Dulbecco's advice and sent an application letter to the Director of the Institute, Professor Niels Kaj Jerne, who offered me a two-year contract.

In the winter of 1971, I thus found myself surrounded by immunologists in this small town located in the middle of Europe. I must admit that the first year in the Institute was not easy for me. I had a continuing interest in work on SV40, but I was also keenly aware that I would not be able to take much advantage of the circumstances if I isolated myself by pursuing that subject. I therefore decided to study immunology in the hope of finding an interesting project.

An immunologist, Dr. Ita Askonas, and a geneticist, Charles Steinberg, were very helpful to me on my entering the new field. By the end of 1971, I was introduced to the great debate on the genetic origins of antibody diversity. I felt from the beginning that I could contribute to resolving this question by applying the recently invented techniques of molecular biology, namely, restriction enzymes and recombinant DNA. Initially I worked only with my skillful technicians, Monica Shöld and Rita Schuller, but was soon joined by Drs. Nobumichi Hozumi, Minoru Hirama, and Christine Brack. Later, as my research group expanded, I had the good fortune to work with many capable postdoctoral fellows and devoted technical assistants. In addition, Charles Steinberg was a very important collaborator and consultant, particularly in the initial phase of the research.

Looking back, the research progressed with amazing speed from 1974 to 1981, the year I left Basel. We all worked hard and had had a great deal of fun. Our work resolved the long held debate on the genetic origin of antibody diversity. It turned out that this diversity is generated by somatic recombination of the inherited gene segments and by somatic mutation. To our very good fortune, Director Niels Jerne was quick to understand the importance of our approach and became a staunch supporter of the research in its early phase.

In the beginning of the 1980's I began to feel that the great mystery of antibody diversity had been solved, at least in its outlines. I thought that it might be good to change my environment to launch into a new project. I also recalled that I had initially come to Switzwerland with the intention of staying for two years and then returning to the United States. Fortunately, I received a few offers from the United States and decided in 1981 to take a professorship at the Center for Cancer Research at M.I.T. Professor Salvador E. Luria, Director of the Cancer Center, was extremely helpful, not only in bringing me to M.I.T., but also in providing me with a beautiful laboratory.

The research projects on which I had decided concerned two major problems. One was to investigate the role of somatic rearrangement in the activation of the rearranged antibody gene, and the second was to extend the research in Basel to "the other half" of the immune system, namely, to the antigen receptor of T cells. Fortunately, we could contribute to the understanding of both problems by discovering a tissue-specific transcriptional enhancer in the immunoglobulin heavy chain gene and by identifying, cloning, and sequencing genes coding for the polypeptide subunits of the T cell receptor. A particularly intriguing development made during the latter study was the identification of a gene that led to the discovery of a new T cell receptor, gamma delta. While the function of the T cells bearing this receptor is currently unknown, data accumulated during the past year in our laboratory as well as many other laboratories suggest that these T cells may be involved in an entirely new aspect of immunity.

When I look back on my scientific career to-date, I am amazed at my good fortune. At every major turn, I met scientists who were not only at the very top in their own fields, but who also gave me insightful advice and generous help. I am most grateful to Professors Itaru Watanabe, Renato Dulbecco, Niels Kaj Jerne, Charles Steinberg, and Salvadore Luria. I also wish to extend my unending gratitude to many colleagues and technical assistants.

My parents were firm believers that education is the best asset that parents can give to their children. I am deeply grateful to them for their outstanding support of my study and professional career. I am extremely grateful to my wife, Mayumi, whom I married in September 1985 for her devotion, interest, encouragement and criticism. I also wish to express my sincere thanks to my first wife, Kyoko, for her limitless devotion during my days in La Jolla and Basel.

I have been fortunate enough to receive many professional honors which include: The Cloetta Prize of Foundation Professor Dr. Max Cloetta, Switzerland (1978), Warren Triennial Prize of the Massachusetts General Hospital, U.S.A. (1980), Genetics Grand Prize of Genetics Promotion Foundation, Japan (1981), Avery Landsteiner Prize of the Gesselshat für Immunologie, West Germany (1981), Asahi Prize of Asahi-Shimbun (Asahi Press), Tokyo, Japan (1982), Louisa Gross Horwitz Prize of Columbia University, New York, U.S.A. (1982), The V.D. Mattia Award of the Roch Institute of Molecular Biology, Nutley, U.S.A. (1983), Gairdner Foundation International Awards of the Gairdner Foundation, Toronto, Canada (1983), Person of Cultural Merit "Bunkakorosha" of the Japanese Government (1983), Order of Culture "Bunkakunsho" from the Emperor of Japan (1984), Bristol-Myers Award for Distinguished Achievement in Cancer Research (1986), Robert Koch Prize of the Robert Koch Foundation, West Germany (1986). Albert and Mary Lasker Award, New York City (1987) and NOBEL PRIZE in Physiology or Medicine, Stockholm, Sweden (1987).

From Les Prix Nobel. The Nobel Prizes 1987, Editor Wilhelm Odelberg, [Nobel Foundation], Stockholm, 1988

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate.