NEW YORK (AP) – The phone call came at 4:40 in the morning at Craig Mello’s home in Massachusetts. It was from Stockholm, telling him he’d won the Nobel Prize.

But Mello was already awake. He’d been checking the blood sugar of his 6-year-old daughter, Victoria. She has diabetes – one of the many diseases that Mello’s work may help to treat.

The 45-year-old professor at the University of Massachusetts Medical School in Worcester, and Andrew Z. Fire, 47, a professor at Stanford University, will share the $1.4 million prize for discovering a process that can silence specific genes.

Called RNA interference, it occurs in plants, animals and people. It’s important for regulating gene activity and helping defend against viruses.

Since Fire and Mello published their groundbreaking research in 1998, scientists have made “RNAi” their own tool. It’s a standard lab procedure for studying what genes do.

And researchers are using it to try to develop treatments for a long list of diseases beyond diabetes, including the AIDS virus, cancer, heart disease, asthma, cystic fibrosis, flu, Parkinson’s and Huntington’s diseases, and age-related macular degeneration, a major cause of blindness.

“This has been such a revolution in biomedicine, everybody is using it,” said Thomas Cech, president of the Howard Hughes Medical Institute, for which Mello is an investigator.

“It’s so important that people almost take it for granted already, even though it was discovered fairly recently,” said Cech, who won a Nobel in 1989 for RNA research.

Nobel prizes are generally awarded decades after the work that they honor, so a prize now for a finding published just eight years ago is striking.

But it’s appropriate, said Bruce Stillman, president of the Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y., because the work “is recognized now as one of the really revolutionary changes in the way we think about how genes are controlled.”

Genes produce their effect by sending molecules called messenger RNA to the protein-making machinery of a cell. The messenger RNA directs that machinery to produce a particular protein.

In RNA interference, certain molecules trigger the destruction or inactivation of the messenger RNA from a particular gene, so that no protein is produced. Thus the gene is effectively silenced.

For instance, researchers have shown they can lower cholesterol levels in lab animals by suppressing a gene through RNA interference.

Could this ability to block disease-causing genes produce new treatments?

“In principle it works. In controlled laboratory conditions it works,” Cech said. “And the next five years will tell whether this is a whole new class of pharmaceuticals with the potential to defeat numerous human diseases.”

Mello, who’s still working on RNA interference, said his daughter’s diabetes is a driving force, although he’d started his research before she was born.

“You don’t really appreciate how important the work of the last 50 years or so of modern molecular medicine … has been until you know somebody who is alive and well because of it,” he said.

Fire said the award showed the importance of publicly funding basic research that doesn’t appear to have any near-term payoff. He also said he had not decided how to use his half of the prize money.

Fire, who was working for the Washington-based Carnegie Institution at the time of the discovery, and Mello did their groundbreaking experiment in a tiny worm called C. elegans. They found they could block the effect of a specific gene by injecting worms with a particular double-stranded version of RNA. Usually RNA – ribonucleic acid – has only one strand.

“That was the breakthrough that set the whole field on fire, no pun intended,” Cech said.

While scientists had already known that RNA played a role in gene silencing, they didn’t understand the process. The prize-winning research “was like opening the blinds in the morning,” said Erna Miller, a member of the Nobel committee. “Suddenly you can see everything clearly.”

Jeremy M. Berg, director of the National Institute of General Medical Sciences in Bethesda, Md., which has funded work by Fire and Mello for years, said he had predicted the two men would win this year.

“It’s an example of a discovery of a fundamental biological process that has an almost unlimited number of implications,” Berg said. “The impact has just been steadily growing.”

Monday’s prize was the first Nobel of this year, to be followed by the awards for physics, chemistry, literature, peace and economics.

Alfred Nobel, the Swedish inventor of dynamite, established the prizes in his will in the categories of literature, peace, medicine, physics and chemistry. The economics prize is technically not a Nobel but a 1968 creation of Sweden’s central bank.

Winners receive a check, handshakes with Scandinavian royalty, and a banquet on Dec. 10 – the anniversary of Nobel’s death in 1896. All prizes are handed out in Stockholm except for the peace prize, which is presented in Oslo.

Biotechnology writer Paul Elias in Palo Alto, Calif., and reporter Ken Maguire in Boston contributed to this report.

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AP-ES-10-02-06 1617EDT

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