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The Pioneers of Molecular Biology: Robert Horvitz
	His studies of cell suicide have helped pharmaceutical companies develop new treatments
	By Christine Gorman

Posted Sunday, February 9, 2002; 10:31 a.m. EST
When Robert Horvitz took high school biology in 1960, there was no mention of Watson, Crick or DNA. "We were basically dissecting very dead animals," Horvitz recalls. Although the double helix had been discovered seven years earlier, it still hadn't permeated the scientific, much less popular, culture. By the time he took his first college level biology class at M.I.T. in 1967, however, everything had changed. DNA had taken center stage and the textbook Horvitz and his fellow students studied was the first edition of James Watson's Molecular Biology of the Gene.

Still, Horvitz, who decided to become a biologist, couldn't completely escape working with animals. DNA is after all, just a molecule—albeit an important one. What researchers wanted to know is how the genetic information in a DNA molecule gets turned into an entire organism. Humans are too complex to make good guinea pigs. Viruses seemed to Horvitz rather too simple. So after completing his graduate studies in Watson's lab at Harvard, he headed to England to learn about the nematode, a tiny roundworm known to scientists as C. elegans.

Such nematodes, with fewer than 1,000 cells, are the most stripped-down organism that still has a nervous system. During a postdoctoral fellowship in Cambridge, England, 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 during development than managed to survive.

Was all that seemingly wasted development a fluke or part of the natural order of life? Horvitz, now back in the U.S. and head of his own lab, was determined to find out. By the mid-1980s he and his team had identified several genes that regulated the process of cell death. Once those genes were activated, the cells died on command—in effect, by committing suicide.

The work was fascinating in a morbid sort of way, particularly if you happen to be fond of nematodes. But on February 12, 1992, Horvitz's group made an even more telling discovery. They learned that one of the genes that controls cell suicide in nematodes is almost identical to a gene in humans—and not just any gene, but a gene that plays a critical role in the development of cancer.

For Horvitz, this was the aha! moment. Cell suicide is such an important part of the body's ability to survive and maintain itself that the genes that regulate it hardly differ from one species to the next. Suddenly there was a new way to connect dozens of seemingly unrelated diseases and disorders. Cancer cells don't commit suicide often enough. The neurons of an Alzheimer's patient are too quick to die. These insights are now being used by pharmaceutical companies to develop new treatments for many different diseases.

Horvitz's discoveries also confirmed the importance of basic research—the kind where you don't know in advance in what way your results may be useful. Who would have guessed, 30 years ago when Horvitz began studying C. elegans, that nematodes and humans had so much in common? There's no telling what else the lowly worm has yet to teach us about ourselves.

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