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Robert A. Weinberg


Contemporary oncogene research traces its roots to several distinct lines of work on tumor viruses. The papovaviruses, polyoma and SV40, and the Rous sarcoma retrovirus provided the seminal observations that launched this field by showing that cultured cells infected by these viruses acquire many of the phenotypes of cancer cells, including tumorigenicity. The importance of these observations is hard to overestimate. By infecting cells growing in monolayer culture, an investigator could recapitulate a process that hitherto was thought to occur only in the matrix of a living tissue. With one blow, the process of malignant transformation was demystified.

Equally profound were the insights that this provided into the molecular basis of the observed transformation. The genomes of these viruses encompass only 10−6 of the DNA content of the cell. It soon became apparent that this small amount of genetic information sufficed to orchestrate malignant transformation, being involved in its initiation and maintenance in virus-transformed cells. Indeed, the transforming functions could be ascribed to a subset of the genetic sequences of these various viral genomes.

Malignant transformation could now be understood in terms of a small number of genetic regulators working within the cell to control cell growth. The field of oncogene research represents a playing out of this theme in endless variations. An important chapter in this saga was ushered in by the discovery that the viral oncogene associated with the genome of Rous sarcoma virus derives from a normal cellular gene. This led to the model, vindicated in a...

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