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Craig C. Mello with daughter Victoria yesterday. UMass president Jack Wilson was at rear.
Craig C. Mello with daughter Victoria yesterday. UMass president Jack Wilson was at rear. (Darren McCollester/ Getty Images)
Andrew Fire, a Stanford professor, will split the honor and the $1.4 million in prize money with UMass scientist Craig Mello.
Andrew Fire, a Stanford professor, will split the honor and the $1.4 million in prize money with UMass scientist Craig Mello. (Kmberly White/ Reuters)

UMass scholar shares Nobel for gene silencing

Technique opens path to treat disease

WORCESTER -- Just eight years after his scientific breakthrough, University of Massachusetts scientist Craig C. Mello and a collaborator won the Nobel Prize in medicine yesterday for discovering a way to block the effect of individual genes in cells. The technique, called ``RNA interference," has transformed research into diseases such as Alzheimer's and HIV.

Mello, 45, becomes the first to win the honor at the University of Massachusetts Medical School, which has long labored in the shadows of the research powerhouses Harvard and Massachusetts Institute of Technology to the east. Mello will share the honor and the $1.4 million in prize money with collaborator Andrew Fire , 47, a professor of pathology and genetics at Stanford University.

Mello and Fire's discovery ``has completely transformed how everybody does science in biology," said Dr. William Hahn , an associate professor at Dana-Farber Cancer Institute and a principal investigator in the RNAi Consortium, a public-private initiative based at the Broad Institute. ``You cannot go to a talk, you can't read a paper, you can't read a grant proposal that doesn't use RNA interference."

The discovery of RNA interference, or RNAi, gives biomedical researchers far more control over the behavior of the genes they study. Throughout its life, a cell turns its genes on and off -- like a conductor leading a symphony -- as it needs to accomplish different things. Cells use RNA interference naturally, but researchers can manipulate it to switch off genes in human cells, providing a way to study what genes do, and creating the possibility of a new class of drugs that could shut down known genetic troublemakers.

It is unusual for the honor to be given out so soon after a discovery, scientists said, because the committee typically likes to see how important it will turn out to be. But scientists said yesterday that many expected the work -- which is used every day in labs around the world, inspired new companies, and even led to new drugs now in clinical trials -- to be recognized soon. Already, researchers are testing RNAi in the treatment of age-related macular degeneration, a disease that causes progressive loss of vision.

Speaking yesterday in the packed conference room of a gleaming new research building that anchors the campus, a visibly humbled Mello said his day had begun early. The phone rang in his Shrewsbury home, but his wife answered and said it was a ``crank call." He went to check on his 6-year-old daughter Victoria, who has juvenile diabetes, when the phone rang again. This time, he answered, and a caller from Sweden told him the news.

``I think my first words were, `You have got to be kidding,' " Mello said.

However, Mello said he had a sense that his work with Fire could win the Nobel Prize. ``I knew it was a possibility, but I didn't really expect it for perhaps a few more years," Mello told the Associated Press.

Mello's interest in science dates back to boyhood visits to his paleontologist father's office at the Smithsonian Institution's National Museum of Natural History in Washington D.C. There he saw the enormous fossils of the stegosaurus as well as the shells of the microscopic creatures his father specialized in.

He was entranced that life on earth had such a long and varied history, where whole groups of animals had come and gone over many millions of years.

In high school, he decided to study biology after hearing about work in which scientists genetically engineered bacteria to produce human insulin. Ironically, this is the very kind of insulin that keeps his daughter alive today.

Mello earned his bachelor's degree from Brown University and his doctorate from Harvard. His colleague, Fire, earned his bachelor's in mathematics from the University of California, Berkeley, and then at age 19 he went to MIT, where he earned his doctorate. Fire was at the Carnegie Institution in Washington, D.C., when he did the work that led to the Nobel.

Before its discovery, RNA interference, also called ``gene silencing," had perplexed other scientists. In 1990, for example, a scientist added a gene for purple pigmentation to petunias in hopes of making them more purple, but found instead that the flower turned white -- as if the pigment gene had been switched off. Mello and Fire observed a similar phenomenon when doing experiments on microscopic worms.

In 1998, Mello and Fire co authored a seminal paper in the journal Nature that unraveled the bizarre phenomenon, identifying a special kind of double-stranded RNA that could shut down individual genes.

The implications grew as researchers in other labs discovered that the silencing technique could be applied to human cells, allowing scientists to do things they had only dreamed about before: systematically shutting down genes one by one to understand which are essential for diseases to work.

Last year, university researchers and private companies began collaborating in the RNAi Consortium, an effort to speed drug discovery by creating a kind of scientific catalog to help researchers understand how to turn off 15,000 human genes as well as 15,000 mouse genes that are widely used in medical research.

But perhaps more tantalizing is the possibility that RNAi could create a new class of drugs that might work by fundamentally shutting down a faulty gene. The patent for their technique has been licensed to dozens of biotech companies nationwide -- including Alynylam in Cambridge -- where researchers are working to harness the technology for use against diseases from flu to cancer.

Now, researchers are in the midst of human trials for gene silencing treatments for respiratory syncytial virus, the most common cause of pneumonia in infants. There are also plans in the pipeline to apply the gene-silencing technique to hepatitis C, flu, and other conditions.

This is the second time researchers have been recognized for work done within the University of Massachusetts system. Russell A. Hulse and Joseph H. Taylor Jr. won the Nobel Prize in physics in 1993, for work they did at UMass-Amherst. They were working at Princeton University when the prize was announced.

``This is an incredible day for the University of Massachusetts Medical School," said Chancellor and Dean Aaron Lazare .

Mello said he did not know how he would spend the prize money, but said that ``college expenses" would be one possibility.

He said that he wanted to see his discoveries start saving lives: ``I want to get right back to work."

Johnson can be reached at cjohnson@globe.com. Cook can be reached at cook@globe.com.

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