The Nobel Prize in Physiology or Medicine 1975
David Baltimore, Renato Dulbecco, Howard M. Temin
Born: 22 February 1914, Catanzaro, Italy
Died: 19 February 2012, La Jolla, CA, USA
Affiliation at the time of the award: Imperial Cancer Research Fund Laboratory, London, United Kingdom
Prize motivation: "for their discoveries concerning the interaction between tumour viruses and the genetic material of the cell"
I was born in
Catanzaro, Italy, from a Calabrese mother and a Ligurian father.
I stayed in that city for a short time; my father was called into
the army (World War I) and we moved to the north, Cuneo and
Torino. At the end of the war my father, who was in the "Genio
Civile", was sent to Imperia, Liguria, where we stayed for many
years. The life I remember begins at Imperia, where I went to
school, including the Ginnasio-Liceo "De Amicis". What I remember
most of that period, besides my family and the few friends, was
the rocky beach where I spent most of my time during the summer
holiday, and a small meterological observatory, where I used to
spend lots of my free time throughout the year. There I developed
a strong liking for physics, which I put to good use by building
an electronic seismograph, probably one of the first of its kind,
which actually worked.
I graduated from high school at 16 (1930) and went to the University in Torino. Although I liked especially physics and mathematics for which I had considerable talent, I decided to study medicine. This profession had for me a strong emotional appeal, which was reinforced by having an uncle who was an excellent surgeon.
In Torino I was a very successful student, but I soon realized that I was interested in biology more than in applied medicine. So I went to work with Giuseppe Levi, the professor of Anatomy, where I learned Histology and the rudiments of cell culture. For my degree, however, I went to morbid anatomy and pathology. In Levi's laboratory I met two students who later had a strong influence on my life: Salvador Luria and Rita Levi-Montalcini.
All through the student years I was at the top of my class although I was two years younger than everbody else.
After taking my MD degree in 1936 I was called up for military service as a medical officer. In 1938 I was discharged and returned to pathology. A year later, however, I was called up again because of the Second World War. I was sent briefly to the French front, and a year later to Russia. There I had a narrow escape on the front of the Don during a major Russian offensive in 1942: I was hospitalized for several months and sent home. When Mussolini's government collapsed and Italy was taken over by the German army I hid in a small village in Piemonte and joined the Resistance, as physician of the local partisan units. I continued to visit the Institute of Morbid Anatomy in Torino where I joined in underground political activities together with Giacomo Mottura, a senior collegue. I was part of the "Committee for National Liberation" of the city of Torino, and became a councillor of that city in the first postwar city council. However, the life of routine politics was not for me and within months I left that position to return to the laboratory. I also went back to school, enrolling in regular courses in physics, which I pursued for the next two years.
I moved back to Levi's Institute and worked together with Levi-Montalcini, who encouraged me to go to the USA to work in modern biology. My dream was to work in genetics of some very simple organism, possibly using radiations. This dream became a reality after Luria, who had been in the USA since the beginning of the war, and was working in this very field, came in the summer of 1946 to Torino. He encouraged me and offered me a small salary for working in his group. I was urged in this direction by Rita Levi-Montalcini, who was herself preparing to go to another laboratory in USA. So in the autumn 1947 we both embarked for the US.
I went to work with Luria in Bloomington, Indiana, where I shared with him a small laboratory under the roof, to be soon joined by Jim Watson. Within a year I had made two good pieces of work, using my mathematical knowledge, and discovered photoreactivation of phage inactivated by ultraviolet light. This attracted the interest of Max Delbrück, who offered me a job in his group at Caltech.
I moved to Caltech in the summer 1949. I remember that memorable trip from Indiana to California with my family in an old car, with our limited possessions in a small trailer behind. I was fascinated by the beauty and immensity of the USA and the kindness of its people. Reaching the Pacific Ocean in Oregon was like arriving at a new world, an impression that continued and increased as we made our way south to Pasadena. I resolved at that time that I would not like to live anywhere else in the world - a resolution that I changed only some twenty-three years later.
At Caltech I continued to work with phages for a few years. One day I was told by Delbrück that a rich citizen had given Caltech a fund for work in the animal virus field. He asked me whether I was interested. My medical background and the experience gained in Levi's laboratory came back to me and I accepted. After visiting the major centers of animal virus work in the US I set out to discover the way to assay animal viruses by a plaque technique, similar to that used for phages, using cell cultures. Within less than a year, I worked out such a method, which opened up animal virology to quantitative work. I used the technique for studying the biological properties of poliovirus. These successes brought me an appointment first to associate professor, then to full professor at Caltech.
In the late fifties I had as a student Howard Temin, who, together with Harry Rubin, then a postdoctoral fellow in my laboratory, worked on the Rous Sarcoma Virus. Their work started my interest in the tumor virus fields. I myself started working on an oncogenic virus, polyoma virus, in 1958, and continued until now. This work has led to discovering many aspects of the interaction of this virus (and of SV40) with the host cells in lytic infection and transformation.
I moved from Caltech to the Salk Institute in 1962, and in 1972 to the Imperial Cancer Research Fund Laboratories in London. One of the reasons for the latter move was the opportunity to work in the field of human cancer.
My work throughout the years has been strongly influenced by my associates. Giuseppe Levi taught me the essential value of criticism in scientific work, Rita Levi-Montalcini helped me to determine my goals at an early stage; Salvador Luria introduced me to viruses; Herman Muller, at the University of Indiana taught me the significance of Genetics; Max Delbrück helped me understand the scientific method and the goals of biology, and Marguerite Vogt contributed to my knowledge of animal cell cultures. Perhaps more important than all this, the daily interaction through the years with a continuously changing group of young investigators shaped my work. For although I had general goals, the actual path followed by my research was pragmatically determined by what could be done at any given time, and my young collaborators were an essential part of this process. I always did as much as possible of the experimental work with my own hands, but in the later part of my research career this became progressively less feasible, both because the demand on my time increased and because the increasing technical sophistication and complexities of the experiments demanded a great deal of specialized skills.
Since 1962 my scientific life has had the support of my second wife, Maureen, who for some years helped in my experiments. Without her affectionate encouragement and sound advice I doubt whether I would have been able to accomplish what I have done.
From Les Prix Nobel en 1975, Editor Wilhelm Odelberg, [Nobel Foundation], Stockholm, 1976
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.Copyright © The Nobel Foundation 1975
Addendum, August 2005
After I received the Nobel Prize my research interest shifted to the study of naturally occurring cancers. I concentrated on a model system, mammary cancers induced in rats, and I spent some time learning how to work with them. In 1977 I returned to the Salk Institute, where I continued, with some collaborators, in the new direction, concentrating on the normal development of the gland. Using monoclonal antibodies against our cells we could identify several different types of cells, and proposed a role for them in the development of the gland.
During this work I became aware of the major difficulty in trying to identify cell types and their roles in both development and carcinogenesis. It became obvious to me that some major effort had to be made to gain knowledge of the genes active in cells; the determination of the genes present in a given species would be the starting point. I thus suggested the starting of a genome project in two lectures I gave in 1985 and 1986. These suggestions remained without consequences. Thus I wrote a paper to the same effect in Science in 1986. The paper had enormous resonance, at first mostly negative, but very soon converted into positive. In the end it helped the emergence of the genome project.
In 1988 I was asked to act as temporary president of the Salk Institute, and soon I was promoted to regular president, a position I held until 1992. During this time I gave up my lab, in order to concentrate on the needs of the Institute, which was going through a very difficult period. In 1992 I was asked by the Italian National Research Council to organize an Italian Genome Project. For this purpose I spent, in the following years, about half of my time in Italy. The Italian Project produced some results, but was handicapped by the isolation of the researchers and the limitation of facilities and financing. It came to an end after five yeas, and was not renewed.
During these years I collaborated with investigators of the National Research Council and of the National Cancer Institute in Milan. We continued the study of mammary development, using a tissue culture system in which differentiation occurs in vitro. We identified several genes controlling the process, some in a positive, others in a negative way. We also started investigating the changes in gene expression in human breast cancer, using two new approaches for improving the results: one was the isolation of pure cancer cells in order to avoid contamination with genes expressed by various types of normal cells present in a cancer; the other was to adopt the SAGE approach to measure gene expression, in order to avoid the complications of the microarray technology. The results can be interpreted as implicating the mammary stem cells in the origin of the cancer.
At the beginning of 2006, when I will reach 92 years of age, I will give up the Italian connections, and will retire at La Jolla, to follow the work going on at the Salk Institute, and to play the piano.
Renato Dulbecco died on 19 February 2012.
Copyright © The Nobel Foundation 2005
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