PopSci's 2nd Annual Brilliant 10

VICTOR VELCULESCU


Genomics: Johns Hopkins University


His maverick approach ushered in a new way to finger cancer genes.



Victor Velculescu's office overlooks a building where physicians help patients battle tumors. Velculescu, 33, could work there himself—he got his M.D. concurrently with a Ph.D. in human genetics—but early on, he did the math and decided that though treating sick people would give him a hands-on role, he could help more people by discovering what makes cancer tick. Tumors arise from genetic errors in a single cell. The task he set himself was to find those glitchy genes.



One way to find genes is to extract all the DNA from a cell, then identify the individual genes contained within it. That's the method the vaunted Human Genome Project (HGP) used. But though that approach reveals many of the genes within a cell, it doesn't indicate what those genes do or when they are active. Velculescu decided that rather than identifying genes and then trying to figure out their role, he wanted to catch cancer genes in the act, and then identify them. He based his plan on a simple fact: All the active genes in a cell are copied into molecules of RNA. The more RNA copies, the more active the gene. If researchers could gather all the RNA molecules floating in a cancer cell and compare that collection to one from a normal cell, they could identify genes that are overactive in cancer—but working backward from RNA was slow. Velculescu theorized that by paring RNA molecules to the bare minimum and linking those pieces together, he could rapidly characterize and count each one. "It sounded too good to be true," he recalls.



His method, known as SAGE, worked—and 30 times faster than the old one. SAGE was "revolutionary," says Sanford Markowitz, a cancer geneticist at Case Western Reserve; it has so far identified dozens of genes involved in cancer and other diseases. Meanwhile, SAGE suggests the HGP may have vastly undercounted. But infighting ranks low in Velculescu's concerns. "The goal," he says, "is translating this information to ultimately help somebody."



—JR Minkel