The Nobel Prize in Medicine, 2007 was awarded to Mario R. Capecchi, Sir Martin J. Evans and Oliver Smithies (in the words of the Academy) “for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells.” They have made a series of ground-breaking discoveries that led to the creation of an immensely powerful technology referred to as gene targeting in mice. Gene targeting is often used to inactivate single genes, a process known as “gene knockout.” These experiments have helped us understand the roles of numerous genes in embryonic development, adult physiology, aging, and disease. With gene targeting it is possible to produce any type of DNA modification in the mouse genome. Gene targeting has already produced more than five hundred different mouse models of human disorder, which include cardiovascular and neuro-degenerative diseases, diabetes, and cancer. Information about the function of our bodies through out life is carried within the DNA, which is packaged in chromosomes, which occur in pairs- one from the father and one from the mother. Exchange of DNA sequences occur by a process called homologous recombination. Capecchi demonstrated that homologous recombination was possible between introduced DNA and the chromosomes with the mammalian cells. In this manner, defective genes could be repaired by homologous recombination with the incoming DNA. In his attempts, Smithies had discovered that endogenous genes could be targeted irrespective of their activity.
Martin Evans had worked with embryonal carcinoma (EC) cells, which could give rise to almost any cell type. Evans discovered that chromosomal normal cell cultures could be established directly from early mouse embryos, now referred to as embryonic stem cells (ES) cells. The reports which showed the homologous recombination in ES cells used to generate gene-targeted mice were publicized in 1989. Since then, gene targeting has developed into a versatile technology. We can now introduce mutations that can be activated at specific time points, or in specific cells or in organs, both during the development and the adult animal.
Mario R. Capecchi, US citizen, PhD in Biophysics, Harvard University. Presently Howard Hughes Medical Institute Investigator and Distinguished Professor of Human Genetics and Biology at the University of Utah, Salt Lake City, UT , USA.
Sir Martin J. Evans, British citizen, PhD in Anatomy and Embryology, University College, London UK. He is a Director of the School of Biosciences and professor of Mammalian Genetics, Cardiff University, UK.
Oliver Smithies, US citizen, PhD in Biochemistry 1951, Oxford University, UK. He is a Excellence Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.