Photo: U. Montan
Photo: U. Montan
Photo: U. Montan
Mario R. Capecchi
Sir Martin J. Evans
Oliver Smithies
The Nobel Prize in Physiology or Medicine 2007 was awarded jointly to Mario R. Capecchi, Sir Martin J. Evans and Oliver Smithies "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells".
3 Win Nobel in Medicine for Gene Technology
Left, Dan Sears/European Pressphoto Agency; Andrew Weltch/European Pressphoto Agency; Dirk Douglass/Reuters
From left, Oliver Smithies, Martin J. Evans and Mario R. Capecchi.
Two Americans and a Briton won the 2007 Nobel Prize in medicine today for developing the immensely powerful “knockout” technology that allows scientists to create animal models of human disease in mice.
The winners, who will share the $1.54 million prize, are: Mario R. Capecchi, 70, of the University of Utah in Salt Lake City; Oliver Smithies, 82, of theUniversity of North Carolina in Chapel Hill; and Sir Martin J. Evans, 66, of Cardiff University in Wales.
Other scientists are applying their technology, which is also known as gene targeting, in a wide variety of ways from basic research to the development of new therapies, said the Nobel committee from the Karolinska Institute in Stockholm that selected the winners.
The technology allows scientists to establish the roles of individual genes in health and disease. Mice have been likened to pocket-sized humans because they have the same organs and their genes are about 95 percent identical in sequence to humans. Scientists have developed more than 500 different mouse models of human ailments, including those affecting the heart and central nervous system, as well as diabetes, cancer and cystic fibrosis.
Scientists can now use the technology to create genetic mutations that can be activated at specific time points, or in specific cells or organs, both during development and in the adult animal, the citation said.
Gene targeting technology can inactivate, or knock out, single genes to study development of the embryo, aging and normal physiology. So far, more than 10,000 mouse genes, or about half of those in the mammalian genome, have been knocked out, the committee said, and ongoing international efforts will make knockout mice for all genes available within the near future.
Also, gene targeting can be used to study almost every aspect of mammalian physiology, the committee said.
Gene targeting has helped decipher the roles of many genes in mammalian fetal and organ development to unmask secrets of normal biological events.
The three laureates also shared a Lasker award in 2001. They are friends but worked independently, Dr. Capecchi said in a telephone interview.
The scientists began their work in the 1980s and the first reports that the technology could generate gene-targeted mice were published in 1989. The reports involved a rare inherited human disease, the Lesch-Nyhan syndrome, in which lack of an enzyme causes fits of self-mutilation.
The prize was particularly rewarding for Dr. Capecchi, who lived as a street urchin in Italy during World War II and who later had to prove his scientific peers wrong after they rejected his initial grant to the National Institutes of Health in 1980, saying his project was not feasible.
Dr. Capecchi’s mother had lived in a luxurious villa in Florence and had become a Bohemian poet, writing against Fascism and Nazism. She refused to marry his father, an Italian Air Force officer with whom she had a love affair. When young Mario was not yet 4, the Gestapo came to their home in Tyrol, in the Italian Alps, to take his mother to the Dachau concentration camp.
Because she knew her time of freedom was limited, she had sold all her possessions and given the proceeds to an Italian farming family with whom he lived for about a year. When the money ran out, the family sent Mario on his way. He said he wandered south, moving from town to town as his cover was blown. He wandered, usually alone, but sometimes in small gangs, begging and stealing, sleeping in the streets, occasionally in an orphanage.
At the war’s end, the malnourished boy was put in a hospital for a year. During that time his mother, who had survived Dachau, searched hospitals and orphanages for him. A week after she found him — on his birthday — they were on a boat to join her brother in a Quaker environment in Pennsylvania.
His new American family put Mario in the third grade, where as a means of communication his teachers told him to draw murals. As he did, he slowly learned English. Because of the street smarts he developed in Italy, he became a class leader and the boy who beat up the bullies.
He went on to study political science at Antioch College, alternating periods of work and studies. Then he went to the Massachusetts Institute of Technology and Harvard, where he worked in the laboratory of James Watson, the Nobel prize-winning co-discoverer of the structure of DNA, before joining the Harvard faculty.
When he decided to leave Harvard because members of the department did not get along and did not recruit sufficient younger scientists, Dr. Capecchi chose to go to Utah in 1973. Colleagues told him, he said, that he was “nuts” to leave Harvard’s Ivy League splendor. But Dr. Capecchi said Dr. Watson told him he could do good science anywhere.
Dr. Capecchi said the main advantage was that he could work on long-term projects more easily in Utah than at Harvard where there was a push to get results quickly.
Dr. Capecchi said that when he re-applied to the N.I.H. in 1984 for the grant it had rejected in 1980, he was told, “We are glad you didn’t follow our advice.”
After learning he had become a Nobel Prize winner, Dr. Smithies told Agence France-Presse that “it’s actually a rather peaceful feeling of culmination of a life of science.”
Dr. Smithies has credited his interest in science to when he was a boy building radios and telescopes and reading a comic strip featuring an inventor whom he wanted to emulate. He earned a scholarship to Oxford, dropping out of medical school to study chemistry before moving to the University of Wisconsin. Because of a visa problem, Dr. Smithies worked in Toronto for about seven years before returning to Wisconsin. He became a geneticist and moved to the University of North Carolina 19 years ago.
Dr. Smithies is a licensed airplane pilot and is fond of gliding.
Dr. Evans had planned to have an “ordinary day” off work cleaning his daughter’s home in Cambridge, England, where he was visiting when he learned he won the prize. It was “a boyhood dream come true,” Dr. Evans told Agence France-Presse.
Like Dr. Capecchi, Dr. Evans said his scientific career was an upward struggle. In an interview with the Lasker Foundation, Dr. Evans said recognition was important to him because he often was a lone scientist who cried out against the general mood. In applying for grants, he said he was told many of his ideas were premature and could not be done.
“Then five years later I find everyone is doing the same thing,” he said.
Dr. Evans is credited for discovering and isolating embryonic mouse stem cells and for developing a method that would allow the three scientists to put their work together.
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