he 1980s, the term "programmed cell death" was almost synonymous with Caenorhabditis elegans, the tiny, transparent nematode worm whose cell-death program removes precisely 131 of 1,090 cells to form the adult. "What has pushed the field forward is Bob Horvitz's work, which allowed us to look at the process in the worm," says Osborne, who spent a sabbatical year in 1992 in the lab of Horvitz, a Howard Hughes Medical Institute (HHMI) investigator and a professor of biology at the Massachusetts Institute of Technology. "The fact that you have a certain number of cells and can trace their developmental fates and see what happens, and watch under the microscope and predict which cells will die, then isolate genes, has made the field blossom and flourish." Meanwhile, little was known about cell death in other types of animals. When David Hockenbery, Stanley Korsmeyer, and their HHMI group at the Washington University School of Medicine in St. Louis discovered that the proto-oncogene bcl-2 blocks programmed cell death (D. Hockenbery et al., Nature, 348:334-6, 1990), this and other work on bcl-2 refocused attention on apoptosis, contributing to the second blip of interest in the early 1990s. Soon, researchers using worm genes with mutations called "ced" (for cell death abnormal) as probes identified death genes in other animals. "It was a great advance to realize that some [apoptosis] genes in the nematode are similar to genes in mammals," says Hermann Steller, an associate professor of neurobiology and an HHMI investigator at MIT who recently discovered an apoptosis gene in Drosophila melanogaster (K. White et al., Science, 264:677-82, 1994). Little is known about the many-tiered genetic control of apoptosis. Most apoptosis genes under investigation turn the process on or off. "Apoptosis on" genes include ced-3 and ced-4 in C. elegans, and ICE and p53 in mammals. Expression of ced-3 and ced-4 is necessary for the cell death of normal worm dev...
