Found molecular genetics' role in Big C

22-2-1914 — 19-2-2012

RENATO Dulbecco, the virologist and molecular geneticist who unravelled the way in which cancer-causing viruses either transform or replicate in their host cells, has died in La Jola, California. He was 97.

He shared the 1975 Nobel prize for physiology or medicine with Howard Temin and David Baltimore.

Dulbecco believed that the new science of molecular genetics might provide a deeper understanding of cancer and identify routes for controlling or preventing it. When he received the Nobel prize he said: ''While we spend our lives asking questions about the nature of cancer and ways to prevent or cure it, society merrily produces oncogenic substances and permeates the environment with them. Indeed, society does not seem prepared to accept the sacrifices required for effective cancer prevention.''

The scientific community had already applied rigorous controls and even banned some forms of genetic research that seemed potentially harmful. Dulbecco knew his idealistic hope - that societies worldwide would soon actively seek to eliminate causes of cancer - would long remain far from realisation.

Born in Catanzaro in Calabria, southern Italy, Dulbecco grew up in Imperia, Liguria, and studied medicine at Turin University, where his fellow students included Salvador Luria and Rita Levi-Montalcini.

Compulsory military service followed his graduation. Discharged in 1938, he was soon called up again as a medical officer during World War II. After serving in France, he was injured in Russia, spent months in hospital and was then discharged. When Italy was occupied by German forces, he joined the partisans as a physician. In 1945 he was appointed to Turin's postwar council.


Dulbecco then took a course in physics and worked on genetics and cell cultures with Levi-Montalcini. Luria, who was now a bacterial geneticist in the United States, visited Turin in 1946 and suggested that Dulbecco join him. In 1947, both Dulbecco and Levi-Montalcini joined American laboratories.

At Indiana University, Dulbecco developed techniques for studying bacteriophages (viruses that infect bacteria) and made the curious discovery that some phages seemingly killed by ultraviolet light could recover if treated with normal light.

He sought a genetic explanation for this and attracted the attention of Max Delbruck who, in 1949, invited him to join his genetics group at the California Institute of Technology. This began Dulbecco's years of virus research there which, mainly with Marguerite Vogt as his assistant, started with studies of the fundamental biology of the polio virus, exploiting modifications of his phage techniques.


Later that decade, Dulbecco turned his attention to the biology of animal cancer viruses. He set out to unmask the mechanism by which viruses transform a cell into uncontrolled, cancerous form. (This mystery had existed since early in the 20th century, yet the famous transforming agent identified by Peyton Rous in 1911 did not gain recognition as the Rous chicken sarcoma virus - the first animal cancer virus to be isolated - until the mid-1930s. Rous had to wait another 30 years for recognition and a share in the 1966 Nobel prize.)


Using new radioactive labelling techniques, Dulbecco discovered that, depending on the type of animal cell infected, the polyomavirus might enter the cell and (like other viruses) subvert some of the machinery to its own ends and multiply until the cell burst, releasing viral progeny to infect other cells. Or, it might not replicate at all but nevertheless induce cancerous transformation.

He demonstrated that transformation occurred when viral genetic material entered and combined with the host nucleus, taking over and blocking normal genetic-control mechanisms. Insensitive to normal feedback signals from its own membrane and neighbouring cells, the infected cell simply multiplied to form an immortal and ever-increasing cancerous clone. This discovery opened up a vast area of research into the underlying mechanisms of transformation, seen as common to all cancer induction.

In 1972, Dulbecco began work at the Imperial Cancer Research Fund laboratories in London. Appointed deputy director in 1974, he remained there until 1977, when he joined the Salk Institute in La Jolla, California. He became Salk president in 1989 and retired as an active president emeritus in 1992.

Dulbecco is survived by his second wife, Maureen, and two daughters. A son predeceased him.