From Child on Street to Nobel Laureate

By Christopher Lee
Washington Post Staff Writer
Tuesday, October 9, 2007

Mario R. Capecchi's earliest memories are of his mother being arrested by the Nazis.

In 1941, Capecchi, then a young boy living in the Italian Alps, saw the Gestapo haul away his mother, a poet who had allied herself with anti-Fascist intellectuals. The arrest was the start of a remarkable journey for Capecchi, one that included being a homeless street urchin, suffering from malnutrition in an Italian hospital, immigrating to the United States -- and yesterday, winning the Nobel Prize in medicine.

Capecchi, 70, a renowned geneticist at the University of Utah at Salt Lake City, shares the prestigious $1.54 million prize with fellow American Oliver Smithies, 82, a native of England now at the University of North Carolina at Chapel Hill, and Sir Martin J. Evans, 66, of Cardiff University in Wales. The trio won the award for research on how genes can be manipulated in mice to better understand disease in humans.

But it is Capecchi's story that is particularly striking.

He was only 3 when his mother, Lucy Ramberg, a member of a group of artists known as the Bohemians, was sent to the Dachau concentration camp in Germany as a political prisoner for pamphleteering against Nazism and fascism. Anticipating the arrest, Ramberg, who never married Capecchi's father, an officer in the Italian air force, sold her possessions, giving the money to a peasant family that she asked to care for her son. But the money ran out in a year.

"They didn't have the resources to keep me and maintain their own family," the scientist said in a telephone interview yesterday. "So I went on the streets."

Capecchi moved from town to town, hungry most of the time and occasionally living in orphanages or traveling with gangs of other homeless children who stole food from carts while other members of the group distracted the vendors. "Just surviving from day to day pretty much occupies your mind," he said in a 1997 interview with the Salt Lake Tribune.

He spent years on the streets and nearly died of malnutrition in a hospital near Bologna, where he lay naked and feverish on a bed, existing on a daily bowl of chicory coffee and a small crust of bread. His mother, who was liberated from Dachau by U.S. troops in 1945, found him at the hospital after searching for more than a year. She showed up on his ninth birthday, carrying a Tyrolean outfit for him, complete with a small cap with a feather. She took him to Rome, where he had his first bath in six years.

"I still have the hat," he said in a 1996 lecture in Japan.

In 1946, Capecchi's uncle Edward Ramberg, a physicist living in a commune in Bucks County, Pa., sent money so that his sister and nephew could come live with his family in the United States.

"I was here one day, and the next day I went to my first school," Capecchi said.

After attending Quaker schools through high school, Capecchi earned a bachelor's degree in chemistry and physics from Antioch College in Ohio in 1961 and a doctorate in biophysics from Harvard University in 1967. At Harvard, he worked in the lab of molecular biologist James D. Watson, one of the co-discoverers of the structure of DNA.

Capecchi and the other researchers were honored for work they did in the 1980s investigating how mouse genes can be manipulated to better understand and model serious illnesses in humans such as cancer, high blood pressure, diabetes and Alzheimer's disease.

Working largely independently, Capecchi and Smithies developed a method known as "gene targeting" that allowed them to inactivate or modify genes in mice. Meanwhile, Evans discovered that stem cells could be extracted from mouse embryos and cultivated to grow into any cell type.

Applying the new method to Evans's cells, the scientists were able to introduce specific gene modifications in mouse embryos, creating animals with human diseases such as cystic fibrosis. Such mice, now commonly used in laboratory experiments, could help researchers better understand the origins of disease and find treatments and medicines.

"If you want to make a model of a specific human disease, you can," Smithies said yesterday in a telephone interview. He added: "You can make a mouse to make it have that disease, and then you have something which you can try to help cure or at least alleviate it."

The groundbreaking work is considered to have laid the scientific foundation for efforts to eradicate some diseases in humans by manipulating genes.

The National Institutes of Health has long funded Capecchi's and Smithies's research, but not always. In 1980, it rejected Capecchi's grant application for experiments on the feasibility of gene targeting, deeming them unlikely to succeed and "not worthy of pursuit," Capecchi recalled in a 1996 speech. He pressed ahead anyway.

"Mario has a strong, independent mind and a willingness to pursue good ideas and important projects despite adversity," said Ray White, a professor of neurology at the University of California at San Francisco who was a colleague of Capecchi's for two decades as they worked independently on mouse and human genetics. "There was real opposition to his ideas and disbelief that his approach would be fruitful," he said.

Asked if Capecchi's work is likely to lead to gene modifications in humans to prevent or fight diseases, or even to bring genetic enhancements, White noted that other methods of genetic modification have proved more practical in human cells than the method that Capecchi took to such heights in mice.

"But nothing is impossible," White said. "That's Mario 101."

Staff writer Rick Weiss and staff researcher Madonna Lebling contributed to this report.

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