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Posted: 10:05 AM- This report was first published Sept. 16, 2001.
The view from Mario Capecchi's office at the Eccles Institute of Human Genetics offers a sweeping, picture-window look at the Salt Lake Valley and a swirl of clouds above.
Sitting at his desk on a recent weekday with sunlight streaming in and the hustle of the University of Utah going on below, the noted molecular biologist read quietly from a research paper in his hands. He was deeply involved in the findings and looked up only after a visitor addressed him by name -- twice.
"Oh, yes," the genetics and biology professor said, smiling, offering a nearby chair. "I was concentrating."
A heightened sense of solitude under a Western sky is the reason Capecchi came to Utah about 30 years ago. At that time, the early 1970s, it was "a quiet place to do good research."
But good research barely describes quality of work performed by the Italian-born Harvard-trained geneticist who today wins the 2001 Albert Lasker Award for basic medical research, often dubbed the "American Nobel Prize."
Capecchi, 63, shares the honor with Cardiff (Wales) University's Martin Evans and the University of North Carolina's Oliver Smithies. All three are scheduled to travel to New York in the coming days to accept the award.
"Studies using mice -- particularly Capecchi's development -- are a landmark" in molecular biology, said retired Howard Hughes Medical Institute chief scientific officer Max Cowan from his Maryland home last week. "It changes the face, in one sense, of experimental medicine."
The Lasker Award signals Capecchi and the others as pioneers in the development of lab-based technology used to manipulate the mouse genome with exquisite precision. That manipulation, which over the years has been dubbed gene targeting, is the basis for blockbuster scientific creations called "knockout mice."
Knockout mice are nothing more than designer strains of lab mice with a specific gene that has been disabled or "knocked out." The technique, now performed routinely in thousands of labs around the world, gives researchers DNA-level insight into genetic human maladies like Alzheimer's and cancer tumor growth.
"Using this knockout technology, researchers have now produced animal models for hundreds of human diseases," said 1985 Nobel Prize-winning medical researcher Joseph Goldstein, now chairman of the Lasker award jury.
"Knockout mice also are providing the first clues to fundamental biological questions, such as how the brain develops in the embryo and how the immune system defends the body against invaders," Goldstein said in a recent statement.
Capecchi's experiments started in 1980, despite the federal government's refusal to fund the work. By 1984, his knockout technique -- carrying the scientific name "homologous recombination" -- was ready to be presented at a biology conference.
In 1989, Capecchi grew his first knockout mouse, years after federal grant money was finding its way to his U. department. Today he spends limited time in the lab, mostly serving as a manager. His crew of about two dozen researchers, students and staff maintain a colony of 20,000 mice carrying a couple of hundred different knockout strains.
Disabling a mammalian gene takes two steps. First, scientists snip out the targeted DNA section in a test tube using conventional tools available in the molecular biologists' bag of tricks. Then, they must replace an intact, un-snipped gene inside the mouse DNA strand that is missing a section.
The technique allows labs to breed mice with particular pathologies -- a missing gene that stops the animal from growing a tail, for instance -- and sheds valuable light on how mammals become ill.
"The mouse genome is 99.9 percent similar to the human genome," Capecchi said. "So gene targeting in this field is getting there . . . and eventually we'll have models for human" genetic ailments across the board.
He said he expects his gene targeting method to yield new drugs or medical treatments in about 20 years.
Evans is being honored with Capecchi because he tracked down the mouse stem cells used for the U. researcher's findings. Smithies worked on gene targeting in tandem, but separately, with Capecchi, and developed techniques to create designer lab mice with important genetic changes.
"Mario is a very interesting, individualistic person," Cowan said of Capecchi, who earned notoriety for leaving Boston's ego-filled Harvard Medical School years ago to build up the U.'s biology and genetics program from its meager beginnings. Capecchi also is a Howard Hughes medical investigator, which he performs far from the institute's Maryland location.
Researchers and friends from around world relish Capecchi's rags-to-riches personal story. Born in Verona, Italy, in 1937, Capecchi wandered homeless as a child for years after his mother was deported to a Nazi concentration camp for joining an anti-Fascist, Bohemian enclave. The two reunited after World War II when he was nine.
"The only general interest of this story is that it exemplifies the antithesis of a nurturing environment," Capecchi said in the transcript of a 1996 lecture.
As he boy, he next came to America, spending his school-age years in a commune near Philadelphia being fed a rich diet of Quaker social responsibility. Later, he studied at Antioch College before going to Harvard to train under James D. Watson, now credited with the co-discovery of DNA's double helix structure.
Now that he is established in the West, the soft-spoken scientist -- handsome in an Italian, looks-sharp-dressed-down kind of way -- travels worldwide to lecture but never loses sight of his role as husband and father.
Cowan likes to tell others about Capecchi's remote home tucked high in the city's Emigration Canyon that the Utahn bought with his wife, Laurie Fraser, and teen-age daughter, Misha, in 1979.
"It's only for someone who really likes to 'rough it' during Salt Lake winters," Cowan said. "Two things appeal to him: natural beauty and absolutely meticulous experi- mentation."
Last year, Capecchi was short-listed for the Nobel's medicine prize and is rumored to be in the running for this year's award, given out in October. In 1996 he won Japan's highest scientific honor, the Kyoto Prize, and has no immediate plans to retire.
The 56-year-old Lasker Awards are named for World War II-era philanthropists, the late Albert and Mary Woodward Lasker. It has been given to 63 scientists who subsequently went on to win the Nobel, including four winners in the last three years.
Today's Lasker prize earns Capecchi about a $15,000 honorarium, a bookshelf statue and untold scientific prestige.
Most of all, though, the honor is another way for Capecchi to feel good about leaving the over-competitive halls of Boston to carve out a scientific niche in Utah.
"On the East Coast at the time, there was so much pressure toward daily success that pretty soon that's all you go after," Capecchi said, leaning back in his U. office chair. "Here, I'm just immensely proud of all I've accomplished in the past 30 years."