"Knockout mice" designers win Nobel Prize

By Simon Johnson and Jerker Hellstrom

STOCKHOLM (Reuters) - Three researchers who pioneered the creation of "designer mice" to demonstrate the roles of different genes in human development and disease won the 2007 Nobel medicine prize on Monday.

Mario Capecchi, 70, Martin Evans, 66, and Oliver Smithies, 82, won the prestigious 10 million Swedish crown ($1.54 million) award for helping forge a new and fundamental branch of medicine -- gene targeting.

"Gene targeting in mice 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," Sweden's Karolinska Institute, said in awarding the prize bearing the name of 19th century dynamite inventor Alfred Nobel.

Their work led to the development of mouse "models" of human disease and is widely used to study the function of genes in both disease and in normal biology. It is also a basis for gene therapy -- correcting faulty genes to treat disease.

The Italian-born Capecchi lived as a street urchin and almost starved while his mother was imprisoned in the Nazi concentration camp of Dachau during World War II. He later became a U.S. citizen, as did the British-born Smithies. Evans is British.

Evans, of Cardiff University, laid the groundwork for making so-called knockout mice when he discovered that days-old embryos are made up of super-powerful cells later dubbed embryonic stem cells. Each one of the cells has the power to give rise to all the cells and tissues in an animal.

Evans and colleagues figured out how to genetically manipulate these cells and implant the embryos back into a female mice, which gave birth to genetically altered offspring.

Capecchi of the Howard Hughes Medical Institute and the University of Utah, and Smithies, now of the University of North Carolina, developed precise methods for changing desired genes one by one. These discoveries led to the development of deleting, or knocking out, genes to discover their function.

"If for example, you see a little finger disappear, then you know that gene is important for making little fingers," Capecchi said in a telephone interview.

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In 2001, the trio took the Albert Lasker Award for Basic Medical Research, seen as the U.S. version of the Nobel since many of its recipients have gone on to become Nobel laureates.

Smithies reacted calmly to the award.

"I was not so much excited but rather it was a feeling a peace. That recognizes this body of work of a lifetime, and now I can go on and do what I want," he said in a telephone interview.

"Most of the time you won't get the result you would like, you won't achieve anything very special, so if you don't enjoy what you were doing, you are disappointed at the end of the day," added Smithies, who also designed "knock-in" mice whose genetic manipulation cures them of diseases.

"But if you enjoy what you are doing, then the disappointment is not very great. You will say, 'Ah, the next day it will work'."