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The quiet man

Shy U. researcher is making a big splash in the genetics pool

Mario Capecchi's life is rich with focus, honor and love — three traits he didn't see much of as a very young child raising himself on the streets of Italy during World War II.

At the core of the life he has built for himself is science — specifically molecular biology and human genetics — which contain elements of all three traits, with plenty of creative thinking thrown in. It is in that scientific realm that the soft-spoken co-director of the genetics institute and professor of genetics and biology at the University of Utah has made his mark.

It's a mark that includes some of the highest accolades the world has to offer a scientist, including the 2003 Wolf Prize from Israel, the 2003 International Award for Cancer Research from the Pezcoller Foundation and the American Association for Cancer Research, the 1996 Kyoto Prize in Basic Science from Japan, the 2001 Albert Lasker Award for Basic Medical Research and the 2001 National Medal of Science from President George W. Bush. The list goes on and on.

Mention "gene targeting" and Capecchi's name comes up. When a researcher studies a disease by knocking out or inserting specific genes in a mouse, some of the honor belongs to Capecchi's lab, where the technique was pioneered. When he applied in 1980 for a grant, the National Institutes of Health called the idea "not worthy of pursuit." Four years later, when he'd proved it could be done, a critique of a new proposal noted "We are glad you didn't follow our advice."

Less familiar to his admirers is the "basically shy" man who loves Arnold Schwarzenegger movies, who microinjects cells to very, very loud Patsy Cline, who likes food and exercise in equal portions, is fond of horses but not of riding them and lives with his wife and two dogs, three cats and a bird.

It is his sense of honor, rather than honors, that define the man, according to those who know him best.

"I don't think (the awards have) changed him," says Laurie Fraser, Capecchi's wife of 20 years. "I think he has so many goals for himself for the future. I think he has a hard time staying in the present and actually enjoying some of the happiness the awards have brought him.

"I think he'd be the first to say he came into science at a time when it was starting to expand. I think he recognizes the people coming into science today have a much tougher road. When he came in, the stage was set for work to be done. Not as many people were in molecular biology."

That's not to say he has no ego, she adds. "He's not puffed up, but I'd say he's got a strong ego. He's proud and sure of what he wants to do in the future. He's not into status symbols, but I'd say that scientifically he's self-assured."

Bright start, rough road

Capecchi was born Oct. 6, 1937, in Verona, Italy, a country caught up in "fascism, Naziism and communism." His grandmother was American artist Lucy Dodd, who left Oregon for Florence in her late teens and later raised her three children on her own there when her husband was killed in World War I. Capecchi's mother, Lucy Ramberg, was a poet of rising note who'd studied at the Sorbonne, becoming a lecturer in literature and languages. She spoke many languages fluently. She joined a group of artists called the Bohemians, who openly opposed fascism and Naziism.

His father was an officer in the Italian air force.

Capecchi was a baby when Hitler's forces started shipping artists to concentration camps. His mother sold everything and took the money to an Italian family. Would they, she wondered, use the money to care for Mario if she was taken away?

Her plans proved wise; she was shipped to Dachau concentration camp in Germany.

Capecchi spoke of those days in a lecture he made when he won the Kyoto prize, his words captured forever in a pristine white-cloth-covered book that he lends casually to a reporter he hardly knows. The family raised wheat for a living. When the money dwindled, they turned Mario out to run the streets with other homeless youths in the heart of the war.

He was 4 1/2 years old.

Capecchi doesn't shy away from speaking of those days, but his words are vague, leaving much to the imagination. As he sits in his small, book-lined office in the genetics building on campus, his soft voice becomes still softer, his smile fades for just a minute.

"I have vivid memories," he says. "Some horrible. But they are snapshots, not a continuum."

At some point, he was hospitalized, one of hundreds of children dying of malnutrition in a hospital that couldn't adequately feed or treat them.

His mother found him on his ninth birthday. He hadn't bathed in years. (She would die, a woman who never recovered mentally from the suffering she'd endured in Dachau, on his 50th birthday in 1987.)

The duo made the two-week-long boat journey to America. He remembers seeing the Statue of Liberty. Their destination was a Quaker commune near Philadelphia, which his uncle helped found and that flourishes still.

"It was a huge culture shock," he says. "I went from a completely nonsocial environment to one that was completely social — everyone knows everything."

Each family had its own house on a vast plot of shared land. They ate together, worked together, played together. They were of all races and religions, though the founders were Quakers. In that "fairly conservative area," they were viewed with suspicion.

He had his first sit-down meal ever the day he arrived. Someone passed him a bowl of peas and he ate it all. He didn't know he was supposed to pass it on.

He spoke not one word of English but started third grade the next day.

Learning by doing

At Antioch College, Capecchi was a political science major with a minor in mathematics — for one quarter. "I found not much science in political science."

Antioch was unusual. Students studied for a quarter, then worked for a quarter, starting with broad-interest jobs that gradually narrowed to reflect the student's developing interest. Capecchi's was science.

By the time he got to Harvard for postgraduate work, he had plenty of working experience in it. As a graduate student, he was in on the early steps of an exciting, developing field, molecular biology.

When he graduated, he immediately joined the Harvard faculty.

It was "the place to be," he laughs. "They were shocked when I came out here."

His mind was busy. He longed to "work on things I knew would take a long time to develop." The University of Utah wooed him in 1973 with the promise that he could take that time. Harvard back then, he recalls, was the land of quick results. And he was not fond of the rivalry between many of the Ivy League school's staff. It was too competitive, at times mean-spirited. He had come from a gentle community where everything was done, from raising food to hand-digging a swimming pool, by working together. "When you don't get along, it's kind of glaring."

He believed — still believes — that "caring human contact is important in terms of human health." Utah seemed to promise that. And wide-open spaces, as well.

A new family

Capecchi and Laurie Fraser met at the University of Utah. An art-major-turned-biology-major from California, she even worked for a time in Capecchi's lab.

The childhood they forged for their daughter, Misha, was very different from Capecchi's. He is, he admits, protective. But he brought one quality he learned in Italy to parenting. He wanted Misha to be self-sufficient. She is.

She grew up near Salt Lake City, in an unpretentious but unusual home in the mountains, where snowfall meant a brisk walk uphill to the front door.

Misha learned to amuse herself and was good with crafts, with her hands.

When she was a little older, they worried about her socialization, so they moved to a house in town. They still own both.

She attended high school at his alma mater, a Quaker boarding school in Pennsylvania. "Quakers don't believe in things. They believe it's what you do with your mind and spirit that's important," Capecchi says. It was a message he and Fraser passed on.

Ask Misha what it was like to have a noted scientist as a father and she pauses. He was gone a lot, she says. But he made time for her.

They played soccer and hiked. She spent hours in his lab, which she loved because of the brightly colored Post-It notes that were stuck everywhere. She grew up knowing the basics and importance of gene targeting "but not in an overbearing way."

She's in college in California but in the middle of last-minute preparations for a yearlong trip to Italy, where she'll work on an organic farm.

While colleagues of Capecchi like Suzanne Mansour describe him as "the smartest person I've ever known," and some predict he'll one day win a Nobel Prize, Misha describes a father who's "emotional but very reserved."

He draws science into every aspect of life, she says, and "takes situations from a very scientific point of view."

He also talks to her "a fair amount" about what he's doing. Last summer, she worked in his lab, and she understands it better now.

Much of their time together was spent "working out" and hiking. They run together. And the three of them like to eat out "a lot."

He's "grouchy" only if he doesn't get to exercise. And, she adds, he sometimes "zones out" in front of the TV.

Fraser and Capecchi like to travel together, walk their dogs in the evenings and talk politics. (They're both fairly liberal Democrats, she says.) They love good food, "but we don't cook very well because we don't make time for it," she says. "But Mario's a good cook. I think a lot of biochemists are; the skills are similar."

He spends his days at the genetics institute; she hangs out at a horse farm for both work and pleasure. She hoped horses would be a love the family could share, but while Capecchi and Misha like the animals, they lack Fraser's passion.

Their friends are divided 50-50 between scientists and "horse" people. He's "equally comfortable" with both groups, she says. And "pretty quiet with both groups."

There's no question Capecchi is shy. But his eyes sparkle with humor. Ask Fraser to describe his sense of humor, though, and she fumbles for words, then suggests you ask one of his close friends, perhaps the neurobiologist with a similar wit.

"I think he has sort of a sarcastic sense of humor without the mean," Fraser says. "Sort of a play on words. Mario is blessed with a pretty good demeanor; he's happy most of the time. He has a good sense of humor and he enjoys laughing."

Kay Higgins, his lab manager, can't define his humor either but knows it when she sees it.

It comes out with no warning. He simply launches into rare but funny stories about things that happened. Then he disappears back into his office. Around Christmastime, he came out of his office carrying a beautifully wrapped box he'd received. Open it, he urged.

Inside were mice finger puppets, their dance controlled by his fingers through holes in the box's bottom. "I started laughing and he started laughing. Now it's in his office on a shelf. I don't think he ever showed anyone else. He has a good sense of humor that's not predictable. I think I happened to be nearby when he wanted to share it with someone, really."

Fraser doesn't have trouble explaining other Capecchi traits. "He is very kind," she says. "He is very respectful of other people and gives people a lot of room.

"I think he doesn't communicate his ideas or his personality to other people very easily. He does that better in science than in the personal arena.

"He's a generous person. But trusting is a different word. I think he more easily trusts women than men."

It is from her husband, she says, that she has learned patience. "I think his patience has been very helpful for him. The other thing — sometimes a bad quality and sometimes a good quality — is he's incredibly tenacious. He will not give up."

A day in the office

Capecchi starts each day with a run. When he was younger, he ran marathons.

When Fraser and Capecchi met, he was "in the lab all the time," she says. These days, administrative work takes up much more of his time. Even before that, he was already doing more writing than bench work. His roster of published articles is impressive.

Fraser thinks he misses the lab work, but "he doesn't make changes to go back," she says, "so I'm not sure."

Higgins and Linda Oswald, his administrative assistant for 12 years, share gatekeeper duties. Is now an OK time to talk to Mario? colleagues ask. It's not that he's moody. "The word that comes to mind is 'focused,' " Oswald says. "You'll get his full attention when he's through with what he's working on.

"He gets going on something and everything else gets totally ignored until that particular project is finished."

Despite his focus, he's not particularly organized. "He knows where everything is, though it looks like a cyclone hit."

He's demanding but fair, they say.

"He's very straightforward," says Higgins. "He has high expectations, but if you know what you're getting into, you're fine. It's what you would want for yourself anyway. He will ask you to do something and expect it to be done well."

He is "insistent" about his exercise time. Every day, he slots three hours to go to the fieldhouse to work out, whenever he's finished his morning tasks.

When Mansour started in Capecchi's lab, he was extremely involved in the work, and the multidisciplinary team itself was smaller than it is now. Capecchi, she says, listens more than he talks. But "if you listen hard, it's always quite worthwhile."

"He was very important to me when I started here," says Mary Beckerle, now deputy director of the Huntsman Cancer Institute. Besides enjoying working with someone of his growing renown and knowledge, "he really embraced me. I think he is this incredibly wonderful person. He's quiet but has a generous spirit that's really nice."

Capecchi is known for his "steady, consistent appreciation for excellence and quality. That's so important for how this place has developed. He is a role model for how to do science," Beckerle says.

Some scientists get discouraged by the big questions, she adds. "Technology has made it easy to do things, to generate data without getting to the next level of understanding, so you can get caught up in lots of small results."

Capecchi admits he shuns little questions, which yield little results. He's a big-picture guy.

In faculty meetings, he's quiet. Then adds "the incisive, he's quiet but often contributes "the incisive, conclusive comment," Beckerle says. "Some people misunderstand him," perhaps thinking he is stand-offish when he is, in fact, shy. "He is brilliant, very insightful, and he integrates things in very creative ways."

In a ceremony at the U. inviting Capecchi to Israel for the Wolf Prize, an Israeli official called him a "genius." Dr. A. Lorris Betz, U. senior vice president of health sciences and dean of the medical school, called him a "roving ambassador" for the U. because of his international acclaim.

Capecchi himself is more prosaic.

"Science is a funny thing. As soon as you've done it, you forget it. Yesterday's results are already achieved and you preoccupy yourself with the things you want to do.

"Besides. Past accomplishments have no bearing on whether you get the grant" to continue research.

E-mail: lois@desnews.com