2 U.S. Scientists Share Nobel

By Rick Weiss
Washington Post Staff Writer
Tuesday, October 3, 2006

Two American scientists -- one of whom graduated from Fairfax High School -- awakened early yesterday to learn they will share a Nobel Prize for their discovery of a gene-regulating mechanism inside cells, an advance that in just eight years has revolutionized genetics and led to several experimental treatments for diseases.

Craig C. Mello of the University of Massachusetts Medical School in Worcester -- whose father, a paleontologist, served for years as an associate director of the National Museum of Natural History -- and Andrew Z. Fire of Stanford University's School of Medicine will share the $1.36 million Nobel Prize in Physiology or Medicine for their serendipitous discovery of RNA interference, or "RNAi."

In a series of experiments on nearly microscopic soil-dwelling worms, conducted at the Carnegie Institution of Washington's laboratories in Baltimore, the team stumbled upon a naturally occurring mechanism that allows cells to shut down individual genes.

That mechanism, RNAi, appears to have first evolved more than a billion years ago, helping plants and fungi defend themselves against invading viruses. But in more complex organisms, including humans, that molecular machinery has taken on new and more complicated functions. Chief among them is the delicate job of shutting down a cell's own genes once those genes have completed a task.

After discovering the mechanism, Fire, Mello and others quickly figured out how to harness it. Today RNAi is an essential tool for scientists trying to understand the functions of various genes -- just turn one off and see what happens. And it is at the core of several young biotechnology companies developing therapies that work by turning off troublesome genes.

"One of the exciting things about this work is that even though it's only eight years since their paper was published, it already has obvious therapeutic potential," said Jeremy M. Berg, director of the National Institute of General Medical Sciences, the branch of the National Institutes of Health that funded much of the work.

Mello said he missed the 4:30 a.m. call from Sweden because his wife picked up the phone and quickly hung up, believing it was a prank. When it rang a second time a few minutes later, she called out "Don't answer it -- it's a crank call!" Mello said in an interview.

Cautiously optimistic, but fearing it was a friend with a bad sense of humor, he picked up the phone anyway. Before long, he was putting in an early wake-up call to his parents, who now run an organic farm in Rixeyville, Va.

It was Mello's Fairfax High School biology teacher, since retired, who set him on his path as a scientist, his mother, Sally, said later in an interview.

The work that won Mello, 45, and Fire, 47, the coveted prize began in the mid-1990s, when they and others were experimenting with "antisense RNA," a then-promising method for modulating the activity of genes inside cells.

Genes are stretches of DNA, each one bearing a molecular code that directs the production of a particular protein such as a hormone or enzyme. But for a gene -- which is made of DNA -- to make a protein, it must work through an intermediary molecule called messenger RNA.

Antisense RNA technology used synthetic strands of RNA to deactivate messenger RNA, effectively blocking a gene's activity and preventing production of a particular protein. But that process never worked as well as scientists had predicted.

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