The 2007 Nobel Prize in physiology or medicine is awarded to Drs Mario R. Capecchi, 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. Their work has made it possible to modify specific genes in the germline of mammals and to raise offspring that carry and express the modified gene. The toolbox of experimental genetic methods developed by Capecchi, Evans and Smithies, commonly called the knockout technology, has permitted scientists to determine the role of specific genes in development, physiology, and pathology. It has revolutionized life science and plays a key role in the development of medical therapy.

The discoveries
Martin Evans identified and isolated the embryonic stem cell of the early embryo, the cell from which all cells of the adult organism are derived. He established it in cell culture, modified it genetically, and reintroduced it into foster mothers in order to generate a genetically modified offspring. Mario Capecchi and Oliver Smithies, independently of each other, discovered how homologous recombination between segments of DNA molecules can be used to target genes in the mammalian genome and developed methods to generate genetically modified mice. Such animals have become indispensable in medical research. Furthermore, the knowledge concerning stem cell biology and gene technology obtained during the research that led to the "knockout mouse" has changed our understanding of normal development and disease processes and identified new avenues for medical therapy. Fig. 1 shows the general strategy for gene targeting in mice.

The 2007 Nobel Prize in physiology or medicine is awarded to Drs Mario R. Capecchi, 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. Their work has made it possible to modify specific genes in the germline of mammals and to raise offspring that carry and express the modified gene. The toolbox of experimental genetic methods developed by Capecchi, Evans and Smithies, commonly called the knockout technology, has permitted scientists to determine the role of specific genes in development, physiology, and pathology. It has revolutionized life science and plays a key role in the development of medical therapy.

The discoveries
Martin Evans identified and isolated the embryonic stem cell of the early embryo, the cell from which all cells of the adult organism are derived. He established it in cell culture, modified it genetically, and reintroduced it into foster mothers in order to generate a genetically modified offspring. Mario Capecchi and Oliver Smithies, independently of each other, discovered how homologous recombination between segments of DNA molecules can be used to target genes in the mammalian genome and developed methods to generate genetically modified mice. Such animals have become indispensable in medical research. Furthermore, the knowledge concerning stem cell biology and gene technology obtained during the research that led to the "knockout mouse" has changed our understanding of normal development and disease processes and identified new avenues for medical therapy. Fig. 1 shows the general strategy for gene targeting in mice.

Mario R. Capecchi
1/3 of the prize
USA
University of Utah; Howard Hughes Medical Institute
Salt Lake City, UT, USA
b. 1937 (in Italy)

Mario Capecchi is interested in the molecular genetic analysis of mammalian
development, with emphasis on neurogenesis, organogenesis, patterning of the
vertebral column, and limb development. He also contributes to the modeling of
human disease in the mouse, from cancer to neuropsychiatric disorders.
Capecchi is credited with developing a powerful technology known as gene
targeting. This technology has allowed scientists to engineer mice with
conditions such as cancer, heart disease, Alzheimer's disease, cystic
fibrosis, and high blood pressure—a feat that has revolutionized the study of
human disease.

Sir Martin J. Evans
1/3 of the prize
United Kingdom
Cardiff University
Cardiff, United Kingdom
b. 1941

"These studies showed the close relationship between these "EC" cells and
normal mouse embryos but it was not until 1981 after my return to Cambridge
that together with Matt Kaufman he was able to isolate similar cells from
normal mouse embryos. Subsequently we rapidly demonstrated, together with my
student and post-doc Liz Robertson and student Allan Bradley, that these cells
which became known as "Embryonic Stem Cells" (ES cells) were able to be used
to fully regenerate fertile breeding mice from the tissue culture cells and
that these could therefore carry mutations introduced and selected or screened
for in culture. This is now the basis of all the mouse knockout and targetted
genetic manipulation"

Oliver Smithies
1/3 of the prize
USA
University of North Carolina at Chapel Hill
Chapel Hill, NC, USA
b. 1925 (in United Kingdom)

Work in my laboratory over the past 10 years has focused on developing animal
models of human genetic diseases. Homologous recombination (gene targeting) is
used to alter a chosen gene in a pre-planned manner in mouse embryonic stem
cells (ES cells) while they are in tissue culture. The genetically altered ES
cells are then injected into normal mouse blastocysts which are introduced
into pseudo-pregnant mice to complete their development. Chimeric mice are
born which transmit the altered gene to their offspring. By the use of this
procedure, they have made mouse models of cystic fibrosis (one of the most
frequent single gene defects in Caucasians) and of Éø-thalassemia and &
Eacute;¿-thalassemia (among the most frequent world-wide single gene defects)，