The 2007 Nobel Prize in Medicine and Physiology was awarded Monday to three scientists whose work now enables researchers worldwide to create "designer mice" that have transformed the study of human disease.
Although the men worked separately, the techniques they pioneered have enabled scientists to create genetically engineered mice and use them as a living biological workbench to tinker with individual genes, identify their functions and test experimental therapies.
"It's hard to imagine a more appropriate or more wonderful choice than this," says Eric Lander, director of the Broad Institute of MIT and Harvard.
Martin Evans of Cardiff University in Wales; Mario Capecchi of the Howard Hughes Medical Institute and the University of Utah; and Oliver Smithies of the University of North Carolina were recognized for discoveries used in "virtually all areas of biomedicine," the Nobel Foundation says.
What gives the work its power, Lander says, is how useful it is. "You want to study a mutation that causes Alzheimer's disease?" he asks. "Make a mouse that has that mutation. You want to study the genetics of diabetes? Make mice with genes that may play a role. Want to study a gene whose function you don't know? Make a mouse in which the gene gets knocked out, see what happens."
For Capecchi, who spent his early childhood on the run from pro-Nazi fascists in Italy while his mother was imprisoned in the Dachau concentration camp, the award caps a remarkable journey. Released from Dachau in 1945, his mother found the 9-year-old naked and filthy in a village hospital.
After emigrating to the USA and graduating from Antioch College, he went to work for James Watkins at Harvard, co-discoverer of the double helix structure of DNA, the biochemical backbone of all life.
At Harvard and later in Utah, he learned how to change genes inside mouse cells. Smithies had gotten there first but credits Capecchi with making the process more reliable and efficient.
For his part, Evans discovered embryonic stem cells — the master cells in mouse embryos that build the whole animal — and how to alter them so that desired genetic changes would be passed from one generation to the next.
"He didn't know how to change genes," Smithies says. "We knew how to change any gene we wanted. We were able to learn how to generate a mouse with that change."
Work done by Smithies' wife, UNC's Nobuyo Maeda, demonstrates the power of the discovery. Maeda developed a line of "knock-out" mice lacking a gene, ApoE, that helps balance the body's supply of cholesterol. Mice without the gene get clogged arteries, no matter what they're fed. Smithies says these mice are widely used by drug companies attempting to find new drugs to treat heart disease.
"It's hard to think of any therapy that hasn't benefited from this work," says the University of Colorado's Thomas Cech, president of the Howard Hughes institute.
The use of human embryonic stem cells has been controversial in the USA because embryos must be destroyed. President Bush placed limits on federal funding of the research.
"There are certainly ethical concerns, which are not trivial," Cech says. "But it's a big leap from mouse to man. And when it comes to curing something like cystic fibrosis, muscular dystrophy, a devastating blood disorder, mutations that lead to cancer or Alzheimer's, there's widespread enthusiasm that if this could be done safely, some people would gain comfort."