Monday, Aug. 20, 2001

Life Preserver

By Christine Gorman

Biologists, like the rest of us, don't like to think a lot about death. Whether it occurs in a fruit fly, a lab mouse or a human, it's usually taken as proof that something has either worn out or gone badly wrong. So when a trio of researchers in the 1970s promoted the idea that the normal development of an organism might depend on the routine death and elimination of large numbers of cells--a process they called apoptosis--the concept seemed pretty farfetched. Why would Mother Nature make a lot of perfectly healthy tissue only to throw most of it away?

But the idea intrigued H. Robert Horvitz, of the Massachusetts Institute of Technology, who thought he had the perfect lab specimen to test the hypothesis--a tiny worm called C. elegans whose entire being consists of fewer than 1,000 cells. During a postdoctoral fellowship in Britain, Horvitz helped to trace the appearance and ultimate fate of every single one of those cells during the worm's development from fertilized egg to adult. That work revealed that many more C. elegans cells were produced than managed to survive.

What really caught the attention of the scientific community, however, was when Horvitz, by then at M.I.T., proved that apoptosis was actually programmed into the worm's genes. In other words, the death of individual cells is a fundamental part of the worm's development. And that's not just true of worms. It soon became clear that there were nearly identical genes for apoptosis in all complex life forms, including humans.

These days it seems that wherever biologists look they find apoptosis playing a starring role. Neurologists watch in amazement as thousands upon thousands of neurons get weeded out in the developing brain. Cancer researchers now realize that the reason many tumors form is because they have forgotten how to die. Apoptosis may also provide important clues in the understanding of such widely different conditions as AIDS and Alzheimer's disease.

Horvitz believes there's a larger lesson here about the importance of basic research. "Time and again discoveries come up in unexpected ways," he says. "You don't always know what's going to come out until you do it." Certainly no one could have predicted that a tiny worm would make possible such far-reaching insights into the very nature of life.