Discovery of oncogenes: The advent of molecular cancer research

In their classic paper on the identification of the transforming principle of Rous sarcoma virus (RSV) published 1970 in PNAS (1), Peter Duesberg at the University of California, Berkeley, and Peter Vogt, then at the University of Washington, Seattle, drew a seemingly simple yet groundbreaking conclusion. When they analyzed the genomic RNAs of transforming, acutely oncogenic RSV and of transformation-defective (td) mutant derivatives, they found that all transforming virus stocks contained two classes of RNA subunits, a larger one (a) and a smaller one (b), whereas the nontransforming yet replication-competent mutants contained the smaller b subunits only. Duesberg and Vogt concluded that the larger a subunit contained the transforming principle of RSV. Based on this and on subsequent structural comparisons of the a and b subunits of biologically cloned viruses, the transforming principle was defined by the remarkably simple equation a − b = x and was later termed src (for sarcoma). The first biochemical identification of a cancer gene was achieved, initially in a chicken virus. However, the principal proof of a physical underpinning of the cancer gene hypothesis had tremendous impact on a fundamental challenge of medicine, decoding the molecular basis of human carcinogenesis. The genetic and biochemical investigations of the chicken tumor virus RSV and the persistent search for its transforming principle are a classic paradigm in cellular and molecular cancer research (2, 3). In 1911, Peyton Rous at the Rockefeller Institute in New York discovered the first virus—later termed RSV—that could induce solid tumors in infected fowl, demonstrated by experimental transmission of sarcomas using cell-free filtrates of tumor extracts (4). This seminal discovery started the field of tumor virology (2, 3, 5). However, almost half a century had to pass before the first quantitative biological tools were developed to study the biology of …