Chicago Tribune - October 3, 2006
Peter Gorner, Tribune science reporter, pgorner@tribune.com

Instead of deep purple or deep red, the blossoms were partially or entirely white, and investigation revealed that the flowers' own genes and the new ones had somehow been turned off.

Other scientists applied the petunia research first on tiny roundworms and eventually on human cells. On Monday the Nobel Prize for Physiology or Medicine was awarded to the two American scientists who finally worked out the mechanism involved, opening up a promising new avenue for treating diseases.

Andrew Fire of the Stanford University School of Medicine and Craig Mello of the University of Massachusetts Medical School were honored for their revolutionary discovery of RNA interference, a fundamental mechanism for controlling the flow of genetic information.

Working on a millimeter-long worm species, Fire and Mello found that double-stranded molecules of ribonucleic acid can "silence" specific genes--a process now known to be one way in which the body naturally stops genes from producing unwanted proteins.

Since Fire, Mello and colleagues published their discovery in 1998, this silencing process has become a widespread research tool. Using RNA interference, scientists now can quash the expression of one or more genes in laboratory animals at any point in development. That helps them figure out what the genes do, as well as how and when some birth defects and other disorders develop.

RNA interference also has the potential to treat many diseases--not only those caused by harmful genes, but also those caused by infectious organisms whose genes might be selectively shut down.

Reached at his home in Shrewsbury, Mass., Mello said the award came as a surprise. "Both Andrew and I are fairly young, 40 or so, and it's only been about eight years since the discovery," he said.

At a news conference, Fire said he thought the speed of the award was largely due to the pioneering work of many other scientists. "Science is a group effort," said Fire, who conducted the research while at the Carnegie Institution.

"When we started in the field, there were a lot of other people working. We looked at this complicated jigsaw puzzle and put a piece in."

The stuff of genes is called DNA. Stored in the cell nucleus, this genetic material determines everything a cell will make, do or be. But to get its orders out to the cell, DNA needs a template, a complementary version of itself. This is RNA.

Acting as a messenger, RNA directs the cell to build a particular protein. "DNA makes RNA makes protein" is a central tenet of molecular biology.

In recent years, however, evidence had been mounting that RNA molecules have additional functions in regulating protein production. But how the different RNA types varied was a mystery.

In their 1998 paper, published in Nature, Fire and Mello announced it was a matter of structure. Protein-coding RNA consists of a single string of molecules, while inhibitory or regulatory RNA contains a twisted pair of strands.

Formed into short snippets, this double-stranded RNA dupes the cell into destroying a gene's messenger RNA before it can deliver the command to produce a protein.

Scientists speculate the mechanism developed hundreds of millions of years ago to protect against viruses that sometimes create double-stranded RNA when they replicate.

With this discovery, the ability to dramatically reduce an individual protein became as easy as sneaking an RNA molecule into the cell with a sequence that matches the RNA a researcher wants destroyed.

Several pharmaceutical and biotech companies are conducting research into potential therapies based on this technique.

The first application to reach clinical trials with humans is in the treatment of macular degeneration. RNA interference also has been shown to reverse induced liver failure in mouse studies, and researchers recently reported they have used it to silence the expression of the AIDS virus in mice.

RNA interference does not appear to interact with DNA, which may alleviate some patients' concern about treatements that alter their genetic makeup, as in gene therapy.

A major supporter of Fire and Mello's research has been the National Institutes of Health, particularly the National Institute of General Medical Sciences, which has given them $8.5 million so far.

"If you look back at the petunias, it wasn't until Fire and Mello's work that researchers realized what was going on," said Jeremy Berg, director of the institute.

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Tribune news services contributed to this report

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