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Liz Martin, Deseret Morning News
Dr. Mario Capecchi, left, is congratulated on Monday by Dr. Ray Gesteland, vice president of research at the U.'s Eccles Institute, for his Nobel Prize.

University of Utah scientist Mario R. Capecchi has won the 2007 Nobel Prize in medicine, an honor he shares with two other scientists for their work manipulating mouse genes to study disease.

Capecchi, 70, pioneered a technique to "knock out" specific mouse genes in the early 1980s.

The distinguished professor of human genetics and biology at the U.'s Eccles Institute of Human Genetics shares the award with Oliver Smithies of the University of North Carolina and Sir Martin Evans of the University of Cardiff in Wales.

A visibly moved Capecchi waved the audience to sit down during one of several standing ovations at a news conference the U. called in his honor Monday morning at the institute. "You'll embarrass me," he said, smiling.

While other speakers lauded him, Capecchi's words of praise were for the many young scientists with whom he's worked over the years in his lab and his mentor and fellow researchers, including Smithies and Evans, with whom he claims a warm collaboration. He also praised the U. for its willingness to be patient as he pursues projects that take, in some cases, many years.

When asked about Capecchi, associates and friends used words you would associate with cutting-edge research, like "brilliant" and "outstanding." But they also mentioned how shy, soft-spoken and unassuming the man is. And several spoke of his quirky sense of humor, which was on display several times during the news conference.

He said his wife, Laurie Fraser, nearly didn't answer the phone when it rang at 3 a.m. because the ring sounded off and she figured it must be a "bogus" call. It was, in reality, the secretary of the Nobel Committee, calling from Stockholm, Sweden. "He had a very serious voice, so I took it seriously," he joked.

While he called it a "marvelous surprise," Capecchi and Fraser are very grounded. While a standing-room-only crowd packed into the auditorium at the institute to honor her husband, Fraser went to work with horses and cattle, where she was likely mucking manure as he was being lauded, he said.

He once described himself to the Deseret Morning News as a man who loves nothing more than Arnold Schwarzenegger movies and who has "very, very loud" Patsy Cline playing in the background when he works in his lab.

Because of an embargo on the news, he had to wait a half-hour before he could call and tell his daughter Misha he'd won, he said.

"This is one of the proudest days in the history of the University of Utah," said Dr. A. Lorris Betz, vice president over health sciences. "It is the ultimate honor in medicine." It is also the "first-ever" Nobel awarded to someone working at the U. for work produced at the U.

"Gene targeting truly changed the course of medical research," U. President Michael K. Young said. "It has brought hope ... to millions of people worldwide."

The award is just one more example, Young said, of Capecchi's "life that reflects passion to do good in the world."

That passion to do good is perhaps more striking because Capecchi's childhood took place in a world that was far from sunny. He was born Oct. 6, 1937, in Verona, Italy, the son of an American-born, "quite remarkable" poet, Lucy Ramberg, and an Italian airman. His grandmother was American artist Lucy Dodd.

An instructor at the Sorbonne when World War II broke out, Ramberg was part of a group of artists called the Bohemians "who thought they could wipe out fascism and Nazism with a pen," Capecchi said. They wrote and distributed pamphlets, and Adolf Hitler's forces began sending them to concentration camps as political prisoners.

Before she was shipped to Dachau, Ramberg sold her belongings and gave the money to a friend so he could take care of Mario, then a toddler. When the money ran out a year later, the boy was turned loose, at age 4 1/2, to survive however he could.

"You take care of your own family first," Capecchi said without rancor, after humorously saying "everybody get out their hanky," when asked to recount the remarkable tale of his childhood.

When American soldiers liberated Dachau in 1945, Ramberg was one of the few survivors and spent more than a year searching for her son. She finally found him, desperately ill, in a hospital south of where they had lived. It was his ninth birthday. (She would later die on his 50th birthday.)

They returned a short time later to America, where he grew up on a Quaker commune co-founded by his uncle. Although they had their own house, they shared meals and labor and the value of education and hard work. There he learned English and began what was to be a lifelong love affair with learning.

Capecchi earned his bachelor's degree in chemistry and physics from Antioch College — where students alternated semesters working and in the classroom — then earned his doctorate in biophysics from Harvard, where he completed his thesis work under his mentor, Nobel laureate James D. Watson, who with France Crick determined the structure of DNA.

Capecchi was an associate professor of biochemistry at Harvard when the U. wooed him to Utah in 1973 with the promise he could work on long-term projects and look for "big answers to big questions." Too many researchers, he said, are forced by the question "what's new" to tackle "little questions."

Capecchi, Smithies and Evans each achieved acclaim for gene targeting, the ability to inactivate or change specific genes in mice to see how they affect health and disease. Their work has important implications for diabetes, heart disease, cancer and virtually every type of disease.

"The knockout mice technology which they developed has completely transformed the landscape of biomedical research," said Jeremy M. Berg, director of the National Institute of General Medical Sciences in the National Institutes of Health, which has for years supported some of Capecchi's research with grants.

But it didn't always. In 1980, when Capecchi first applied for a grant related to gene targeting, he was turned down and told it wouldn't work. Within a couple of years, he proved it would, and when a subsequent grant was awarded, NIH officials praised him for persisting, despite their advice.

Gene targeting reaches into nearly every aspect of biomedical research, Berg said. "The number of the field they haven't touched is very small. Every human disease, where there are genes of interest for one reason or another, one of the first things they do is make a knockout mouse strain and see what the impact is."

The technology used has changed and become more sophisticated over the years, making the process more robust and reliable, he said.

To use the technique, researchers introduce a genetic change into mouse embryonic stem cells. Those cells are injected into mouse embryos. The mice born from these embryos are bred with others to produce offspring that have the genetic alteration.

"Gene targeting has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come," said the citation for the $1.54 million prize.

Capecchi's work has uncovered the roles of genes involved in organ development in mammals, the committee said. Evans has developed strains of gene-altered mice to study cystic fibrosis, and Smithies has created strains to study such conditions as high blood pressure and heart disease.

Besides the cash prize, Young joked Monday that Capecchi and any future U. Nobel Prize winners could count on receiving their own special parking spots on campus. In Capecchi's case, though, he wondered whether the space should be by the genetics institute or the gym. Capecchi is avid about exercise, scheduling certain dedicated hours each day to running and working out at the campus fieldhouse.

Because last year's Nobel Prize in Medicine was awarded to Americans Andrew Z. Fire and Craig C. Mello for work with RNA, Capecchi said the early morning call was a "complete surprise." The award "usually jumps around," and he didn't expect to see another in molecular genetics for years.

He may have been the only one at the U. who was shocked. The U. has been on "Capecchi Nobel watch" for several years, convinced his breakthrough would one day be recognized. And when the call came, they sprang into action, organizing events including a more private reception with staff and friends later in the day.

Meanwhile, Susan Sample, of the U. public affairs department, was helping to field calls from the media, including "lots of requests from Italian media" also proud to claim the latest Nobel Prize winner.

Capecchi's list of previous awards is long and impressive, including the Albert Lasker Award for Basic Medical Research and the National Medal of Science, America's highest award for lifetime achievement in research. He's also received Israel's highest honor for medical research, the Wolf Prize in Medicine, as well as the Pezcoller Foundation-American Association for Cancer Research International Award for Cancer Research. In 2005, he was honored with a March of Dimes prize in developmental biology.

A scientist at the Eccles Institute of Human Genetics at the U. medical school, Capecchi also serves as co-chairman of the Department of Human Genetics and helped found the Brain Institute at the U. He holds a presidential endowed chair in health sciences and is a member of the National Academy of Sciences.

As for the future, Capecchi said his lab is working on a project that will "take at least another 20 years." And he plans to be there, he said, adding with a small smile, "I hope."


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