North Carolina Medical Researcher Wins Nobel Prize

Oct 08, 08:30 PM

Current Headlines: CHAPEL HILL, N.C. _ Sunday was an ordinary day for Oliver Smithies, 82. He flew his glider over Chapel Hill, took his wife to lunch and crafted a response to a committee that had denied his latest grant proposal.

On Monday, the scientist was awakened at 5 a.m. by a call from Stockholm, Sweden. He had won the Nobel Prize.

Smithies, a British-born professor of pathology and laboratory medicine at the University of North Carolina at Chapel Hill, shares this year's prize in physiology or medicine with two other scientists _ Mario Capecchi of the University of Utah's Howard Hughes Medical Institute and Sir Martin Evans of Cardiff University in Wales.

The three developed methods for manipulating genes and creating designer mice now widely used in labs all over the world. The work accelerated the field of genetic medicine and laid the foundation for today's research into gene therapy. It is used to study human disease such as cystic fibrosis, cancer and heart disease.

A UNC-CH faculty member for 19 years, Smithies began his work at the University of Wisconsin in the 1980s. The three scientists worked independently but shared information along the way. Gene-targeting allowed the researchers to use "knock-out mice," in which specific genes were removed to understand the effect of the missing gene. The first mouse with manipulated genes was born in 1989, and since then, more than 10,000 different genes in mice have been studied using the technique, the Nobel citation said.

Smithies spent Monday morning at his lab, where he was bombarded by calls from reporters in Russia, France and Germany. He fielded a call from the Swedish Embassy that included an invitation to appear at the White House. His colleagues in the lab brought a bouquet of coral roses and yellow lilies. They threw together a party, but Smithies could barely get off the phone to attend. A yellow sticky note from his assistant said, "Ice cream is melting ... Come!"

"I feel rather peaceful," he said in an interview in his small, cluttered office, where little toy mice perch on his bookshelf alongside boxes of mint tea bags. "I've been working at the bench for more than 50 years and it's nice to find that people appreciate what you've done. It feels like what a lot of people have mentioned _ a capstone on one's career."

Later in the day, he was greeted by the cheers of scientists, doctors and students at a balloon-decorated atrium in UNC's Lineberger Cancer Center, where carrot cake was served in his honor at a reception.

"There is no doubt that this work will lead to new therapy in virtually every disease that has a genetic basis," said Dr. Etta Pisano, a vice dean in UNC's medical school. "That is really not overstating the importance of this discovery."

At a news conference, his postdoctoral fellows and lab technicians crowded in with digital cameras. He was modest about the accomplishments, saying he gets "a nice little glow" whenever he opens a scientific journal and sees that his methods _ now taken for granted _ are being used by scientists across the globe.

"It's quite a marvelous feeling to have been involved in that work," he said in his British accent.

Smithies' Nobel Prize had been expected by his colleagues for years. In 2001, he and his fellow Nobel winners won the Albert Lasker Award for Basic Medical Research, often a precursor to the Nobel. "People at various times have said you're nominated," Smithies said, "and I got used to the fact that nothing ever happened."

UNC-CH Chancellor James Moeser said the honor could not have happened to a more deserving scientist or a more decent human being. Smithies' discoveries were revolutionary, Moeser said. "His work and that of his colleagues has fundamentally changed the science of genetic medicine," he said.

Peter Agre, a 2003 Nobel Prize winner in chemistry and vice chancellor for science and technology at Duke University, said he is humbled by Smithies' work.

"That man is a real scientist," Agre said. "I consider myself a science wannabe in comparison. They got it right this time."

Stuart Bondurant, former UNC-CH medical dean who recruited Smithies, said: "You can't believe his warmth, magnetism and generosity. He is literally beloved by hundreds of people who've worked with him and around him."

Outside Smithies' lab, a map of the United States is dotted with pins marking the location of proteges who worked under Smithies. Bondurant said the scientist was never one to be secretive about his work. "He sought to disseminate every single discovery he made so others could use it."

Smithies has the ability to speak plainly about the complicated business of gene manipulation, which, in the early days, was thought to be impossible in mammals. He did much of the work by hand and sometimes had to build his own machines to manipulate the genes.

"Imagine a book with a thousand pages, and each page has a thousand letters and now you have a library with a thousand of these books. ... What the three of us devised was a way to say, well, that thing you've got in volume 230, I'm interested in Page 96 and at the bottom of Page 96 there's this word, I don't understand what it means. Change it and see what happens. And that's what we found we could do."

Smithies, who made his most important advances after age 60, still works in his lab seven days a week.

He shares the seventh floor of a UNC-CH research building with his wife, Nobuyo Maeda, who does similar work. "He's the hardest worker in the whole lab," said Maeda, also a professor of pathology and laboratory medicine. "We spend most of our time here."

He told the UNC-CH crowd he had no inclination to retire. "I've always said if I were die somewhere, which certainly will happen, it might as well be at the bench, because that's where I'm happy."

The Nobel Prize carries a monetary award of $1.54 million. The ceremony in Sweden will be in December, but Smithies isn't too caught up in the hoopla. His evening plans on Monday? Watching baseball.

"I don't have any particular desire for my life to change," he said. "It's a happy life and we're happy together and we enjoy our work together. Maybe it might be easier to get a little bit of money to be able to do the work, because I still get my grants turned down just like everybody else."

Smithies said he'll resubmit that rejected proposal next month.

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(McClatchy Newspapers correspondent Tim Simmons contributed to this report.)

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(c) 2007, The News & Observer (Raleigh, N.C.).

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