When Phillip Sharp joined MIT in 1974, its new cancer center’s prospects, to some, seemed cloudy at best. Though it was known some cancers run in families, many scientists thought genes — a major cancer center focal area — had a limited role in the disease. Other factors, like viruses, were seen as more critical. “Most people in the field didn’t think we could make major contributions,” he notes.
The doubts gave Sharp, a professor of biology and former center director, some anxious moments. Though he brought strong credentials to MIT, having worked with DNA co-discoverer James Watson, Sharp had to wait almost a year for his first federal grant application to be funded.
But the doubts melted as cancer center members helped revolutionize our understanding of how cells and genes work. Sharp himself helped show that our genes, unlike those in microbes, have long stretches of DNA with no identified role in creating proteins — a discovery that made him co-winner of the Nobel Prize in Medicine or Physiology. Others, like Robert Weinberg, now a professor of biology and member of the Whitehead Institute for Biomedical Research, led in showing that cancers usually stem from genes gone bad.
Today, Sharp, an Institute Professor at MIT, is exploring what may turn out to be another revolution in biology: a phenomenon known as RNA interference.
For casual observers of biological systems, DNA, the molecule that carries our genetic heritage, has always been a genetics powerhouse. Proteins — a group of natural chemicals that are made according to the codes embedded in DNA, and that include hormones like insulin and disease-fighting entities like antibodies — have also been seen as having critical roles.
But RNA, though chemically similar to DNA, had the feel of the “gofer” of genetics. Its chores include conveying to a cell’s manufacturing centers instructions on which proteins to make — necessary, yet hardly the route to scientific stardom.
But if those stereotypes were ever valid, they’re not now. In what Sharp calls a “stunning discovery,” in the late ‘90s scientists stumbled on the fact that snippets of RNA can operate as hormone-like agents — and that the main job of these agents, importantly, is shutting down genes.
These segments of RNA, moreover, have broad impacts. Work at the MIT-Harvard enterprise called the Broad Institute as well as the Whitehead Institute, says Sharp, suggests that “at least half our genes are regulated by small RNAs.”
The findings on small RNA have stirred hopes of using a synthesized version to silence cancer-linked genes, slowing or even curing the disease. But first, scientists need ways to deliver the fragile substance to tumors. A new MIT-Harvard collaboration, the Center for Cancer Nanotechnology Excellence, has taken up that challenge.