The discovery of ras brought one challenge to a close for cancer geneticists: they had purified a mutated oncogene from a cancer cell. But it threw open another challenge. Knudson’s two-hit hypothesis had also generated a risky prediction: that retinoblastoma cancer cells contained two inactivated copies of the Rb gene. Weinberg, Wigler, and Barbacid had proved Varmus and Bishop right. Now someone had to prove Knudson’s prediction by isolating his fabled tumor suppressor gene and demonstrating that both its copies were inactivated in retinoblastoma.
