A perspective on the early days ofRASresearch

The name of the oncogene,ras, has its origin in studies of murine leukemia viruses in the 1960s by Jenny Harvey (H-ras) and by Werner Kirsten (K-ras) which, at high doses, produced sarcomas in rats. Transforming retroviruses were isolated, and its oncogene was namedrasafter rat sarcoma. From 1979, cellularrassequences with transforming properties were identified by transfection of tumor DNA initially by Robert Weinberg from rodent tumors, and the isolation of homologous oncogenes from human tumors soon followed, includingHRASandKRAS, and a new member of the family namedNRAS. I review these discoveries, placing emphasis on the pioneering research of Christopher Marshall and Alan Hall, who subsequently made immense contributions to our understanding of the functions ofRASand related small GTPases to signal transduction pathways, cell structure, and the behavior of normal and malignant cells.