The Nobel Prize in Physiology or Medicine for 2007 has been awarded jointly, well deserved, to the American scientists Mario Capecchi and Oliver Smithies, and to the British scientist Sir Martin Evans, for their pioneer contributions and experimental design resulting in the obtention of the first knockout mice with a gene targeted event, with the specific inactivation of a gene, leaving the rest of the genome intact. Martin Evans described, in 1981, the extraordinary plasticity of pluripotent embryonic stem cells, from the inner cell mass of the blastocyst, thus allowing their maintenance in culture indefinitely, their genetic manipulation and, eventually, their reintroduction in a new blastocyst, without loosing their capacity to differentiate to any of the cellular types found in an adult organism, including the germ line. Mario Capecchi explored, in the 80s, the strategies that allowed him to selectively alter a given genetic sequence, using the homologous recombination procedure, and established, in 1988, the general method of positive-negative double selection. Finally, Oliver Smithies, in 1989, modified a first gene (inactivated) in embryonic stem cells in culture, later obtained a chimera and eventually, through a number of crosses, an animal that, in all of its cells, was carrying the initial mutation of the selected gene.
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