This year's Nobel Prize for Physiology or Medicine has been awarded to two American researchers, Andrew Fire and Craig Mello, for a far-reaching discovery about how genes are controlled within living cells.

The discovery was made in 1998, only eight years ago. It has been recognized with unusual speed by the Nobel Foundation in Stockholm, which often lets decades elapse before awarding its accolade.

The two scientists' finding clarified a series of puzzling results obtained mostly by plant biologists trying to change the colors of petunias. By clarifying what was going on, they discovered a novel and quite unexpected system of gene regulation, and began an explosive phase of research in a field known variously as RNA interference or gene silencing.

This natural method of switching genes off has turned out to be a superb research tool, allowing scientists to understand the role of new genes by suppressing them. The method may also lead to a new class of drugs that switch off unwanted processes in disease. A gene-silencing drug designed to treat macular degeneration is already in clinical trials.

"This was such an obvious Nobel, on everybody's list of discoveries that would receive the prize soon," said Thomas Cech, an expert on RNA and president of the Howard Hughes Medical Institute.

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Bruce Stillman, president of the Cold Spring Harbor Laboratory on Long Island, said the prize was intended to recognize a new field of research, which has had "a spectacular birth and expansion," as well as the discovery by Fire and Mello that started it.

Fire, now at Stanford University, worked at the Carnegie Institution of Washington when he made the discovery. Mello, a frequent collaborator, is at the University of Massachusetts Medical School in Worcester.

Prior to their discovery, plant biologists over many decades had found odd exceptions to Mendel's laws of heredity, including some odd effects produced by injecting RNA into plants. RNA is the less-well-known cousin of DNA. Both are chemicals called nucleic acids, but DNA is longer and more stable and is used by the cell for the archival function of storing genetic information. RNA is shorter and more active, and performs many of the cell's more difficult tasks, such as making copies of the genes in DNA and directing the synthesis of the proteins specified by the genes.

The plant biologists supposed that injecting new RNA might somehow interfere with the protein-synthesizing process but did not understand exactly how to make this happen reliably. Fire and Mello made a decisive advance by showing in roundworms that the injected RNA had to be double-stranded and that the sequence of chemical units had to be the same as or very similar to the gene being targeted. Under these conditions, any gene in the roundworm could be switched off by injecting double- stranded RNA with a sequence of units that corresponded to those in part of the gene's DNA.

Other scientists soon figured out the evolutionary reason for this curious mechanism. It is a defense against viruses, many of which have double-stranded RNA as their genetic material. When a virus enters a cell, its RNA is chopped up and the fragments are used to interfere in the process by which its genes make proteins. Essentially, the fragments are matched to RNA copies of the viral genes that circulate in the cell. Any such matched copies are then destroyed, without damage to the cell's own messenger-RNA, as the copies are known.

The perceived importance of the Fire-Mello finding increased even further when other researchers discovered it had a surprising second dimension. It seems that having evolved this handy mechanism for suppressing a virus's genes, cells then adapted it to controlling their own genes. Both plants and animals, probably independently, evolved genes that do not make proteins but simply generate an RNA molecule. These RNAs, known as micro-RNAs, use the same gene-silencing mechanism as is set off by viruses to ratchet down the activity of many of the cell's own genes.

Micro-RNAs are a novel class of genes whose role is under vigorous study. They seem to be important in processes like embryonic development and in cancer. Gene silencing and micro-RNAs have quickly become a major field of biological research and one that may well attract other Nobel prizes in future. "I think it will be applied quite broadly in anti-cancer therapies in the next 10 years," Stillman said.

Was it unfair for plant biologists who laid the basis for the new field to be excluded from the Nobel prize?

"You have to say they had their chance, and, yes, it was interesting biology, but they didn't trace it to double- stranded RNA," Cech said. "The field exploded after the Fire and Mello paper."

Mello and Fire began collaborating in the late 1980s because both had developed similar techniques for working on the roundworm.

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