By Stephen Smith, Globe Staff, 10/8/2002

An MIT biologist was awarded the Nobel Prize in medicine yesterday for using a tiny worm to unravel the secrets of how human cells die, a discovery that has revolutionized the field of biology and ignited research into treatments for cancer and diseases of the brain.

H. Robert Horvitz, a student of mathematics and economics until the mysteries of biology seduced him, shared the prize with two British researchers, one of them his mentor, the other a longtime collaborator. Together, they pioneered the science of cell death, using parasitic worms called nematodes to understand why and how human cells commit suicide, a process integral to life.

Already, drug company researchers are using this knowledge to develop treatments to prod cancer cells to self-destruct. And the Nobel laureates, along with other luminaries in biology, believe their breakthrough will one day produce ways of stopping the premature death of other cells, which could help the millions of patients stricken with Alzheimer's disease, Lou Gehrig's disease, and other neurodegenerative disorders.

''I would find nothing more gratifying than to learn that one or more of my discoveries led to pharmaceutical treatments or to human cures,'' Horvitz said, five hours after learning that he had received the most coveted award in medical research. ''That would be the dream.''

Colleagues at the Massachusetts Institute of Technology feted Horvitz yesterday with champagne, cake, and effusive words about his scientific generosity, despite his absence; the Chicago native and graduate of MIT and Harvard was vacationing in the French Alps.

''We're really sorry you're not here in person,'' MIT president Charles Vest said, his words directed at a speaker phone sitting next to a photo of a beaming, bespectacled Horvitz. ''But I understand the local champagne may be a little better where you are.''

At 55, Horvitz is the kid among the trio of recipients. Sydney Brenner, Horvitz's mentor during his days studying in Cambridge, England, is 75, and John E. Sulston is 60. They will share $1 million for receiving the Nobel Prize in medicine, the first of the awards to be announced this autumn.

It marked the 56th Nobel awarded to MIT faculty, researchers, and alumni in the 101-year history of the awards.

''It is a day,'' Vest said, ''that should remind all of us of the extreme importance of basic research. It really is the drive to understand the most fundamental processes of science and, in Bob's case, life and death.''

That initial research began with one of the most basic living creatures - the nematode Caenorhabditis elegans.

It was Brenner, now president of the Molecular Sciences Institute in Berkeley, Calif., who established that the nematode could be used as a model organism for studying human biology. To traditionalists in human biology at the time, that seemed like heresy - but Brenner was right.

''It was a very simple organism in which you could address questions of cell biology that at the time would have been difficult in more complicated organisms,'' said Robert Sauer, head of MIT's biology department.

Horvitz and Sulston built on that discovery. Sulston mapped how every cell divided and played a specific role in the development of the nematode and went on to show how certain cells are programmed to die. Horvitz, in turn, discovered and characterized the genes controlling cell death beginning in the 1980s, providing a road map for human disease researchers.

Previously, biologists had trained their microscopes almost exclusively on living cells, figuring that they were the stuff of human life. But, in the past two decades, Horvitz, Brenner, and Sulston produced a tectonic shift in the realm of biology, showing that the death of human cells is indispensable to human life.

''Twenty years ago, everybody thought a dead cell was a dead cell - it's boring,'' said Harvard Medical School cell biologist Junying Yuan, who worked as a junior researcher in Horvitz's MIT lab. ''People associated it with the death of a person. People assumed that cell death occurs in the same way. That couldn't be further from the truth.''

Instead, Horvitz and the other scientists realized that cells are efficient suicide machines - and genetically programmed to be that way. It's a necessary part of life, helping to keep the body in cellular balance, like a snake that must regularly shed its skin.

The suicide process, called apoptosis, shapes developing tissues and organs and refines the central nervous system. Throughout life, the body uses programmed cell death to purge damaged and unnecessary cells.

But how does that happen? It was Horvitz who provided the answer.

In what the Nobel selection committee called ''a series of elegant experiments,'' Horvitz discovered that a genetic program regulates cell death. The identity of two death-inducing genes - a research project in which Yuan played a pivotal role - was published in 1986.

Later, Horvitz described how the delicate interplay between another gene and the two death genes identified earlier confers protection against cell suicide.

Health problems arise when cells that should die instead live, and when cells that should live wind up dying. The result can be cancer, strokes, heart disease, and devastating diseases of the brain.

The understanding yielded by the advances recognized with the Nobel Prize fundamentally altered the terrain of biology.

''It's pretty much in the pantheon of great discoveries in the field,'' said Marc Kirschner, head of the department of cell biology at Harvard Medical School. ''When you deal with a whole new paradigm in biology that's traced back to Bob's experiment, it wasn't a big surprise that he won a Nobel Prize for it.''

In fact, in the sometimes Byzantine world of scientific awards, there were clues that Horvitz was high on the list of potential Nobel recipients. He'd won a series of research prizes regarded as forerunners to the Nobel - sort of like the Golden Globes may indicate who will win film Oscars.

Plus, Horvitz, who is affiliated with MIT's McGovern Institute for Brain Research as well as the Howard Hughes Medical Institute, had been widely published and the recipient since 1972 of $7.1 million in grants from the National Institutes of Health. All of that augured well.

Grants and even publication of scientific results can often be a reflection of respect - and even affection - for a researcher. In the circles in which Horvitz travels, he is renowned for being an eager collaborator, willingly sharing the details of his laboratory labors.

During his 24 years on the MIT faculty, Horvitz has cut a wide path, never content to remain cloistered in a laboratory garret. He teaches classes in genetics and organizes seminars for undergraduate biology students.

His legendary drive is both professional and personal - his father died of amyotrophic lateral sclerosis, better known as Lou Gehrig's disease, and Horvitz helped researchers at Massachusetts General Hospital select patients for treatment studies.

The director of the McGovern Institute, Phillip Sharp, has long admired the precision of Horvitz's mind. He recalls that Horvitz was put in charge of the committee that oversaw the design and construction of Building 68, home to biological research labs and offices. When the committee was choosing an architect, another member argued passionately in favor of a designer different from the one Horvitz preferred.

Horvitz, a copious note taker, dug out his jottings and proceeded to decimate each of the arguments advanced by the other committee member. ''He is one of the most intense human beings I have ever met,'' Sharp said.

That intensity paired with an ability to make ideas concrete give Horvitz an edge over many peers in scientific research, said Harvard's Kirschner, who has known Horvitz since the 1970s.

''He's one of these people you always thought would be a candidate for a Nobel,'' Kirschner said. ''This is not a guy who happened to be in the right place at the right time who just stumbled upon something interesting.''