Originally posted on sciy.org by Ron Anastasia on Wed 04 Oct 2006 03:11 PM PDT
Stanford prof's Nobel-winning work opens up gene research
By Lisa M. Krieger
San Jose Mercury News
When Andrew Z. Fire applied to Stanford University as a Sunnyvale teenager, he was turned down. Decades later, his biological research became so compelling that Fire was recruited to the Stanford faculty, and on Monday he shared the 2006 Nobel Prize in physiology or medicine.
Fire, 47, a professor of pathology and genetics, and Craig Mello, 45, of the University of Massachusetts Medical School, discovered the mechanism that lets the body turn off genes within a cell.
While it has not yet led to medical treatments, it has opened up a promising area of research that could allow scientists to silence genes that cause afflictions from HIV to cancer, bridging the gulf between the Human Genome Project and the death bed. The two scientists' 1998 discovery quickly turned into a lab tool embraced by thousands of researchers around the world.
``It's an obscure molecule doing an obscure process in an obscure organism,'' said Fire at a news conference Monday. ``I didn't know where it would lead. I had no idea.''
Born at Stanford Hospital, and a graduate of Sunnyvale's Fremont High School and the University of California-Berkeley, Fire did much of his ground-breaking work at the small Carnegie Labs in Baltimore, Md.
Now recognized as one of the nation's star biologists, he was recruited by Stanford University three years ago to find ways to apply his basic research to the fast-moving field of medicine. He is Stanford's 15th Nobelist, and the third from the medical school.
``If we can silence genes that contribute to disease, that is very important,'' said Dr. Phil Pizzo, dean of Stanford's School of Medicine.
Fire said he welcomed the chance to work with the doctors and patients at Stanford. ``It was an attractive place to settle, closer to family,'' he added; Fire is married with two young children, and his parents still live in Sunnyvale.
Bemused by Monday's publicity, the self-effacing Palo Alto resident said the announcement -- delivered in a 1:45 a.m. phone call from Sweden -- wouldn't change his life.
``It's a good chance to say `thank you,' '' to Stanford, the Carnegie Labs and the legions of students and colleagues who made his work possible, he said. ``We came into the field where a lot of work was already done. We put a nice piece in the puzzle.''
Fire and Mello will share the $1.4 million prize.
Scientists have puzzled over how the human body -- with a mere 20,000 to 30,000 genes, no more than a worm possesses -- has achieved such elegance and complexity.
It succeeds, in large part, due to cells' natural ability to turn a gene on at one stage of development and off at another, when the gene is no longer needed.
However, there are times when turning on a gene can trigger diseases such as Parkinson's, diabetes, cancer and ALS, or amyotrophic lateral sclerosis, also known as ``Lou Gehrig's disease.''
Silence is golden, if this deadly mechanism can be turned off.
The field of gene silencing had its origins in flowers. In 1990, a biologist sought to make purple petunias a deeper hue by injecting them with genes for coloration. Instead, surprisingly, the blossoms bloomed white. Rather than bolstering each other, the pigment-producing genes interacted by shutting themselves off.
Scientists later created the same effect, using different traits, in the microscopic roundworm. But no one understood how it worked.
Fire and Mello injected into a cell an RNA molecule that blocked the manufacture of a particular protein, thereby shutting off a gene. Voila! They had discovered a silencer, which came to be known as RNA interference.
``Who would have thought that a plant could tell us something about ourselves?'' Fire said.
RNA -- the chemical cousin of DNA, which carries the genetic instructions within each living cell -- was once thought to act as a lowly messenger of information. It has since gained more respect as a controller of gene activity. In 2002, Science magazine called a string of RNA interference discoveries the breakthrough of the year.
The technique is already being used to better understand the human genome, by selectively silencing the voice of one gene in the cacophony of the tens of thousands that pilot a cell throughout its development and death.
The next goal is to harness this mechanism. Several biotechnology companies have sprung up or altered course to capitalize on the ideas of Fire and Mello.
The road to RNA therapies could be long, because all gene therapy carries unknown risks. RNA molecules are difficult to package into a safe and effective drug. The digestive system breaks them down. And they don't readily diffuse into a cell, because of their large size and chemical properties. Further, they can be toxic.
``There will be ups and downs,'' Fire warned, urging a long-term commitment to the field.
``It will take awhile to see where this fits in with other advances.''
Contact Lisa M. Krieger at lkrieger@mercurynews.com or (650) 688-7565.
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