Biologists know death is part of life. Howard Robert Horvitz knows that, for cells, so is suicide.

Horvitz, who won the Nobel Prize in Physiology of Medicine along with research partners Sydney Brenner and John Sulston in 2002, delivered the sixteenth Annual Ef Racker Lecture on Thursday to a packed Call Auditorium. The lecture, “Cell Suicide: Programmed Cell Death in Development and Disease,” outlined the history of modern biology’s understanding of cellular death.

Death can be both a constructive and destructive force. Horvitz explained that programmed cell death sculpts tissue development in plants and animals, diminishing a tadpole’s long tail as the animal matures, for example. Studies have also shown that when cell death is inhibited in mice, the animals suffer severe defects and usually live significantly shorter lives.

But Horvitz got started studying a much smaller animal — the tiny nematode worm Caenorhabditis elegans.

“I’d been advised that it was a professional dead-end [to study C. elegans],” he said. C. elegans have only 959 cells, which makes it “a very beautiful little worm” for genetics experiments — the nematode can go through two or three generations a week. But Horvitz, Brenner and Sulston used the simplicity of C. elegans as an opportunity to map the organism’s entire cellular lineage.

“If you think about an animal where it’s got all these cells dying, what happens to the corpses?” Horvitz asked. “The answer is that other cells come in and swallow them in a process called phagocytosis,” he said.

With phagocytosis inhibited, the corpse cells are strikingly clear on the translucent, slender nematode, appearing “like polka dots on a tie.” Hillary Ellis, grad, noticed that in cells where a gene mutation turned off a protein known as CED-3, no cell death occurred. “Programmed cell death is at least to some extent a process of cellular suicide,” he explained.

A conceptual breakthrough came when researchers discovered that the “killer gene” CED-3 looked like a protease found in humans. “Since there is a human protease that is similar,” Horvitz said. “Humans probably have a protein that acts to promote programmed cell death,” known in mammals as apoptosis.

Researchers were able to work outwards from CED-3 — the fundamental driver of cell death — to discover a series of enabling and inhibiting proteins, each with a familiar human counterpart.

“No gene is an island,” Horvitz said. “And the fact that the human gene could work in the worm said it was interfacing with the same pathway in which it normally works.”

Current research is aimed at using this knowledge to treat previously incurable diseases. Diseases associated with too much cell death, such as neurodegenerative disorders and heart failure may benefit from genetic inhibitors of the process. “On the other hand, for diseases in which there is too little cell death,” Horvitz said, “you can inhibit BCL-2 proteins [to promote cell death].” Cancer researchers have taken a greatly renewed interest in this line of thinking.

“The fact that you can study a worm and learn to treat human diseases is pretty remarkable,” Horvitz said, careful to point out that, at first, his work was “absolutely basic research, where we didn’t even know what to begin to ask about it.” There is a need for government to fund this kind of basic research, he said, since “nobody would have discovered what we did studying any one disease.”

For Horvitz, that C. elegan’s 959 cells can hold the secret to cell death should only make biologists more humble. After all, he said, quoting from an 1882 Punch Almanac, “Man is but a worm.”