No IgNobels here, the 2007 Nobel Prize for Physiology or Medicine has been awarded to Mario R. Capecchi, Martin J. Evans, and Oliver Smithies for a technique that is so incredibly important to modern biomedical research that it’s a wonder they didn’t get the prize before:
This year’s Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.
Gene targeting is often used to inactivate single genes. Such gene “knockout” experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make “knockout mice” for all genes available within the near future.
With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.
It’s hard to overstate how important this technique has become. Using this genetic engineering technology, it is possible to produce mice with a gene or genes specifically knocked out. It is possible to introduce a gene into stem cells and produce mice with that gene’s expression cranked up to high levels. Scientists can then observe the resulting phenotype. The entire process is illustrated below:
I’m actually familiar with Mario Capecchi’s work and have read many of his papers. This is because one of my long time research project involves studying homeobox genes, and Capechhi is known for using this gene targeting technique to produce mice with specific HOX genes disrupted in order to demonstrate their function by observing the phenotype of the resulting mice. He played a major role in working out the “HOX code” in vertebrates. Capecchi’s work with vertebrate HOX genes demonstrates the power of gene targeting to produce transgenic mice.
In the study of human disease, the applications of this technology range from cancer to heart disease to–well, pretty much any disease with a major genetic component. All I can say after seeing this award is: What took the Nobel Prize committee so long?
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