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.