2 Americans, 1 Briton share Nobel Prize in medicine for work with stem cell implications

Two Americans and a Briton shared the Nobel Prize in medicine on Monday for groundbreaking stem-cell research on mice that helped establish the role of individual genes in human ailments including diabetes, heart disease and cancer.

Mario R. Capecchi, Oliver Smithies and Sir Martin J. Evans were honored for a technique called gene targeting, which lets scientists deactivate or modify particular genes in mice.

That in turn lets them study how those genes affect health and disease.

The trio won the Albert Lasker Award for Basic Medical Research, which is often dubbed "America's Nobel," in 2001, and had figured prominently in Nobel speculation in recent years. All were informed early Monday that they had won the prize.

"It was a fantastic surprise," Capecchi, 70, told The Associated Press in a telephone interview from Salt Lake City, Utah, where he is a professor of human genetics and biology.

He said he was asleep when he got the phone call from the Nobel committee secretary at 3 a.m.

"He sounded very serious, so the first reaction was this must be real," Capecchi said.

The Nobel is a particularly striking achievement for Capecchi. A native of Italy, he was separated from his mother at age 4 when she was taken to the Dachau concentration camp as a political prisoner during World War II.

For four years, Capecchi lived on the street or in orphanages, "and most of the time hungry," he recalled in a University of Utah publication in 1997.

Malnutrition sent him to a hospital, where his mother found him on his ninth birthday. Within two weeks they left for the United States, where he went to school for the first time, starting in third grade despite not knowing English.

The citation said the three winners, who will share the coveted 10 million-kronor (US$1.5-million; euro1.1-million) prize, had discovered "principles for introducing specific gene modification in mice by the use of embryonic stem cells."

They used "knockout mice" _ animals whose genetic code has been altered in the lab to either turn on or turn off certain genes that mice and humans share.

The first mice with genes manipulated in this way were announced in 1989. More than 10,000 different genes in mice have been studied with the technique, the Nobel committee said. That's about half the genes the rodents have.

The citation said gene targeting has pervaded all fields of biomedicine and that "its benefits to mankind will continue to increase over many years to come."

Capecchi's work "shed light on the cause of several human inborn malformations," the citation said, while Evans, 66, applied gene targeting to develop mouse models for human diseases.

Smithies, 82, a U.S. citizen born in Britain, also used gene targeting to develop mouse models for inherited diseases such as cystic fibrosis and the blood disease thalassemia, and other diseases such as hypertension and atherosclerosis.

Smithies, a professor at the University of North Carolina at Chapel Hill, said it's "rather enjoyable being recognized at this level" after working on the research for more than 20 years.

He said he hoped winning the Nobel Prize would make it easier to secure funding for other work.

Evans, a professor at Cardiff University in Wales, said one example of how the trio's work was being put to practical use was in understanding why some women are genetically susceptible to breast cancer.

The three scientists mostly worked separately, although they exchanged information about their research. Evans identified embryonic stem cells in mice, while the gene-targeting technique used on those cells came from work by Capecchi and Smithies.

Scientists are also attempting to do this genetic manipulation in human embryonic cells to create a basic research tool, said John Gearhart, a stem cell expert at the Johns Hopkins School of Medicine.

The idea is to make cells with disease-related gene mutations so they can be studied in the laboratory. That could give clues about how the disease develops, and serve as a screening tool for potential therapies, he said.

The issue of human stem cell research has been polarizing in the U.S, where President George W. Bush rejected legislation in 2006 to allow funding of additional lines of embryonic stem cells. Abortion foes oppose embryonic research because it destroys human embryos.

"I think stem cell therapy has enormous potential. It's a crime not to actively pursue it," Capecchi said.

Evans said he understood why some people had qualms about stem cell research using human embryos, but thought these would fade as people understood the science better.

"I believe the whole of the moral angst surrounding stem cells has to disappear," he said. Scientists "are very concerned about the ethical aspects _ but we know better than the general public where these lie."

The science community praised the Nobel laureates for their contributions.

"We're on the cusp of having a much better understanding of the relationship between genes and disease and how, when genes go wrong, they cause disease," said Steve Brown, director of the Mammalian Genetics Unit at the London Medical Research Council. "And that's all down to the techniques that Capecchi, Evans and Smithies developed."

The medicine prize was the first of the six prestigious awards to be announced this year. The others are chemistry, physics, literature, peace and economics.

The prizes are handed out every year on Dec. 10, the anniversary of award founder Alfred Nobel's death in 1896.

Last year, the Nobel Prize in medicine went to Americans Andrew Z. Fire and Craig C. Mello for discovering RNA interference, a process that can silence specific genes.

Since the medicine prize was first awarded in 1901, 90 Americans and 29 Britons have received it.

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AP Science Writer Malcolm Ritter in New York, AP Medical Writer Maria Cheng in London and Associated Press writers Louise Nordstrom in Stockholm, Jill Lawless in London and Bernard McGhee in Atlanta contributed to this report.

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