In the mid-1970s, retrovirus experiments by Harold E. Varmus and J. Michael Bishop demonstrated that cancer-causing virus genes are normal genes that are manipulated by the virus. Inspired by that finding, several researchers—including Mariano Barbacid, Geoffrey M. Cooper, Robert A. Weinberg, and Michael H. Wigler—combed through cancer-causing genes in the genome of cancer cells.
![Robert A. Weinberg, shown here circa 1985, is one of several investigators who played key roles in the discoveries of RAS and RB1. [Photo courtesy of Whitehead Institute for Biomedical Research.]](/view-large/figure/8504115/369photo1.jpeg)
Robert A. Weinberg, shown here circa 1985, is one of several investigators who played key roles in the discoveries of RAS and RB1. [Photo courtesy of Whitehead Institute for Biomedical Research.]
Robert A. Weinberg, shown here circa 1985, is one of several investigators who played key roles in the discoveries of RAS and RB1. [Photo courtesy of Whitehead Institute for Biomedical Research.]
“We were looking for any activity that might transform a normal cell into a cancer cell,” recalls Channing J. Der, PhD, then a post-doc in Cooper's lab and now a pharmacology professor at University of North Carolina, Chapel Hill. Der was tasked with teasing out 30 possible oncogenes from retroviruses. “No one really thought that these genes were the very same genes identified a decade earlier in oncogenic retroviruses,” he says. But in 1982, after performing dozens of experiments, Der and Cooper realized they had uncovered RAS, the first human oncogene. The same discovery happened almost simultaneously in the other researchers' labs.
“It was a revolutionary discovery,” says Allan Balmain, PhD, who heads the cancer genetics program at UCSF and has studied RAS for nearly 3 decades.
Although biologists generally expected to find the opposites of oncogenes, or tumor suppressors, locating one proved tricky because such genes are mutated or lost in tumor cells. “How can you see something that's not there?” asks Philip W. Hinds, PhD, deputy director of Tufts Medical Center's cancer center. But by comparing the DNA of rare eye tumors called retinoblastomas with normal cells, Weinberg's lab, in conjunction with other Boston-area researchers, discovered RB1 in 1986.
These seminal discoveries have yet to lead to the development of RAS- or RB1-targeted therapies. But they have fueled the search for more oncogenes and tumor suppressors—laying the foundation for today's rapid progress in cancer therapeutics.
This article is the third in a 5-part series commemorating the passage of the National Cancer Act in 1971.
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