American, 2 Britons win Nobel Prize for medicine

Team studied nematode to learn how healthy cells are programmed to die


An American and two Britons won the 2002 Nobel Prize in physiology or medicine yesterday for their discoveries, made largely in studies of a tiny worm, of how healthy cells are instructed to kill themselves.

The process, called programmed cell death or apoptosis, is necessary for proper tissue and organ development, but it also plays a role in many diseases.

The three winners are Sydney Brenner, 75, a British citizen who founded the Molecular Sciences Institute in Berkeley, Calif., and who is a professor at the Salk Institute for Biological Studies in San Diego; H. Robert Horvitz, 55, a professor at the Massachusetts Institute of Technology in Cambridge and a Howard Hughes Medical Institute investigator; and John E. Sulston, 60, of the Wellcome Trust Sanger Institute in Cambridge, England.

Horvitz received the news while vacationing in the French Alps. "It was quite enjoyable to have champagne before lunch in France," Horvitz said in a telephone call to a news conference at MIT yesterday.

The three, who worked together in England in the 1970s, will share a $1 million prize. The prize honors their collective work, over the past 30 years, on C. elegans, a 1-millimeter soil worm or nematode.

The investigation of programmed cell death has given scientists better insights into cancer and the way some viruses and bacteria invade human cells, according to the Nobel Assembly of the Karolinska Institute in Stockholm, Sweden, which selected the winners.

The body uses cell suicide in immune cell development and function and in removal of unnecessary or damaged cells.

Improper function of the cell death genes is a hallmark of a number of diseases. In AIDS, heart attacks, stroke and degenerative diseases of the central nervous system, cells are lost from excessive apoptosis, the institute said in its citation.

Other diseases, such as autoimmune conditions and cancer, are characterized by a reduction in cell death, leading to the survival of undesirable cells.

Biologists who study development of the embryo were the first to describe programmed cell death. They noted that cell death was necessary for embryonic development, as in tadpoles' metamorphosis to adult frogs and in the process that eliminates tissue that forms in human fetuses between the fingers and toes.

Apoptosis also shapes the development of the brain, in that a vast number of neuronal cells present during the early stages are gradually eliminated.

The research began in the 1970s when Brenner, a native of South Africa working in England, began studying Caenorhabditis elegans as an experimental model to link genetic analysis to cell division, specialization and organ development.

In subsequent studies, the three scientists discovered that specific genes control the cellular death program in C. elegans. Other studies have shown that the deaths of 131 of the worm's original 1,090 cells are under the control of a particular set of genes. Other studies, including some by the three new laureates, have since shown that corresponding genes exist in higher species, including humans.

"Knowledge of what makes cells die and of what can block the cell-death process in the nematode may help lead to the identification of agents that can regulate the cell deaths involved in a variety of human disorders, such as cancer and neurodegenerative diseases," Horvitz said.

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