Robert Horvitz's Nobel Prize came largely for his work in turning a small, transparent worm that lives in the dirt into an experimental system that has won several others Nobel Prizes since. But his pioneering use of C. elegans came about because he was interested in a problem that was simply easier to address in the animal: how and when cells in an organism choose to die through a process called apoptosis. It was his research in this field that was the focus of his talk at the Lindau Nobel Laureates Meeting.

You might not be aware of it, but many of an animal's cells kill themselves for the greater good of the organism they're part of. In adults, cells with a viral infection or extensive DNA damage (or immune cells that react to the body itself) are induced to commit an organized suicide, slicing up their DNA into short fragments and packaging up their membranes and proteins for easy digestion by their neighbors. The process also takes place during development: we all have webbing between our digits in utero that's gone by birth, and millions of apparently healthy neurons die off to form the adult brain.

This orderly form of death is termed apoptosis, and C. elegans turned out to be the ideal organism to study it. Since the worm is transparent, any cells undergoing apoptosis were easy to spot. Horvitz's co-laureate, John Sulston, had mapped every cell division in the organism, in the process demonstrating that a number of very specific cells underwent apoptosis. Horvitz's lab went to work searching for mutations that kept these cells alive, and found that they grouped into four distinct classes that he said defined the apoptotic process:

Identify the victim

Kill

Get rid of the corpse

Destroy the evidence

(Those last two parts of the process involve the disposal of the dead cell's remains by its neighbors.)

Over time, many of the genes that Horvitz's lab identified were identified in humans, showing that the apoptotic process is pretty ancient, in evolutionary terms, and establishing the validity of studying it in nonhuman systems. That goes a long way towards explaining why his prize came in Physiology or Medicine.

Horvitz has kept his research group focused on apoptosis, and talked a bit about some of their more recent results. One of the key triggers in apoptosis is the activation of an enzyme from the ICE family of proteases, which chop other proteins into smaller fragments. C. elegans has several of these genes, and Horvitz's lab has generated worms that lack them all. This keeps many of the apoptotic cells alive, but not all of them—this suggests that there's another pathway for cell death out there that we've not figured out yet.

But, when the apoptotic pathway is intact, cells seem to need to actively keep it shut off if they want to stay alive. And Horvitz has found that all the specialized cells of the worm seem to handle it in a different way. Skin cells and nerve cells (to give two examples) are quite different, and regulate their genes with distinct combinations of proteins. In worms, most of these different cell-specific regulators converge on a single gene; there are dozens of ways of setting the gene's state, which then determines whether the cell lives or dies.

Horvitz wrapped up his talk by presenting his work as an argument for basic research. The worm he studied was thought to be irrelevant to human health; he tackled his problem with what he termed "formalistic" genetic studies that date back for decades. But, somehow, the work ended up helping us understand processes that are very relevant to human health.