For many years biologists have known that cells die at predictable points during development: tadpoles lose their tails and become frogs; human fetuses lose the webbing between their fingers and toes during prenatal development. However, very little was known about the mechanism until Robert Horvitz ‘68 and other researchers identified and described the process of programmed cell death. Their work earned them the 2002 Nobel Prize in Physiology or Medicine.“At the time [Horvitz began his research], most scientists thought that cells died because they had no choice,” says Craig B. Thompson, chair of the Department of Cancer Biology at the University of Pennsylvania. Scientists believed that cells died when they were deprived of oxygen or damaged by something in their environment.
Building on preliminary work by Sydney Brenner and John E. Sulston, the scientists with whom he shared last year’s Nobel Prize, Horvitz identified specific genes that trigger cell death in the cells of a millimeter-long soil-dwelling nematode named Caenorhabditis elegans. Without the presence of these genes, Horvitz determined, certain cells could live indefinitely. In subsequent studies, he showed that similar genes are present in humans.
“That changed everything,” says Thompson. “It turned out that these cells choose to eliminate themselves.” In essence, they commit suicide. By proving the genetic component, Horvitz was able to demonstrate that programmed cell death is a normal, fundamental, and controlled biological process in cells.
Horvitz’s path to the Nobel was not entirely predictable. As an MIT undergraduate, he majored in mathematics and economics. But, he told the MIT community in a lecture on campus last fall, “it was the late ’60s, and I wanted to do something different.”
To him, “something different” meant moving across town to pursue a PhD in biology in the Harvard University lab of James Watson, who along with Francis Crick had discovered the structure of DNA and confirmed that it carries hereditary information. Watson was collaborating with two other scientists in his lab, Wally Gilbert and Klaus Weber. Horvitz remembers that the troika was “incredibly stimulating. Their combined training left me unafraid to approach any new problem in any context,” he says. Horvitz sustained this mentality throughout his postdoctoral fellowship, which he started in 1974 under Sydney Brenner at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England.