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Of mice and men

The Nobel Prize for medicine awarded this year to three scientists is for their contribution to identifying and isolating embryonic stem cells from mice and for discovering the principles to produce genetically modified mice. While Martin J. Evans was instrumental in identifying embryonic stem cells, Mario R. Capecchi and Oliver Smithies worked independently to develop the knockout technology used for producing genetically modified mice. Using genetically altered mice has become routine practice to identify and understand the role of disease-causing genes and to produce mice exhibiting clinical features of a human disease. Experimental testing of hypotheses concerning the role of a specific disease-causing gene has become a reality. The contribution of genetically modified mice to the development of drugs and finding new avenues for treating diseases in humans has been enormous. Gene targeting holds great promise of finding novel therapies for correcting defective genes in humans based on experimental animal studies. It is now difficult to think of contemporary medical research that does not use gene targeting and genetically modified animal models.

While the roles of Professors Capecchi and Smithies in developing knockout technology used in producing genetically modified animals have attracted much attention, the Evans contribution has not been sufficiently highlighted. It is his identification and isolation of embryonic stem cells from mice that provided the base material for the other two scientists to work on. Although embryonal carcinoma cells seen in tumours have the ability to become any cell type, Professor Evans faced problems using them to create germ cells. His solution? Using cells derived from mouse embryos at a very early stage of embryo development. These cells are today called embryonic stem cells. Professor Evans not only established the germ line transmission of embryonic stem cells but also pointed out the possibility of using such cells for gene modification. He succeeded in demonstrating the production of transgenic animals by introducing a mutant gene of an X-linked syndrome into the embryonic stem cells and identifying them in the offspring. In short, his work laid the ground for a technology that governs today’s medical research. It is vital to encourage research on human embryonic stem cells. The recent decision of the British government and three Europe-based pharmaceutical companies to come together to use human embryonic stem cells for drug safety testing is a fine example. In matters concerning research, scientific merit should be the governing factor.

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