The breakthrough of 'gene targeting'
Almost every human disease has a genetic component and the research that earned this year's Nobel Prize in medicine developed into a practical method of finding out which defective gene gives someone a particular disorder. It also lies at the heart of the international effort to use embryonic stem cells for regenerative medicine.
The three scientists who yesterday claimed the most coveted prize in science pioneered the development of genetically modified mice to understand the fundamentals of human diseases.
Their discoveries led to the creation of laboratory mice to be used as medical models for more than 500 human disorders, ranging from heart disease and neuro-degenerative illnesses to diabetes and cancer. Learning how to modify mice genes using embryonic stem cells has also been pivotal in understanding how human embryonic stem cells may be used in future to treat diseased organs and tissues in situ, rather than relying on surgical transplants.
Sir Martin Evans, 66, of Cardiff University, discovered that embryonic stem cells from mice had the power to develop into any tissues of the body, and developed the techniques of altering their genes using retroviruses. Capecchi and Smithies, working independently, discovered how to target individual genes and to create "knockout" mice, where an individual gene is eliminated to create a mouse model of a human disorder caused by a defective gene.
Goran Hansson, a member of the Nobel committee, said targeting genes had transformed the understanding of human physiology and medicine. "It is difficult to imagine contemporary medical research without the use of gene-targeted models," he added. "The ability to generate predictable designer mutations in mouse genes has led to penetrating new insights into development, immunology, neurobiology, physiology and metabolism.
"The development of novel therapies to correct genetic defects in man will build on the experience of gene modification in mice that is based on the discoveries made by Capecchi, Evans and Smithies."
To date, scientists have selectively knocked out about 10,000 mouse genes – about half of the mammalian genome – in an attempt to discover each gene's function. They hope to complete the process in the next few years and, thereby, understand the role of each gene in the overall function of the body. It was only in 1989 that the strands of the three scientists' researches were brought together to generate the first embryonic stem cells from mice which had undergone gene-targeted modification.
Lord Rees of Ludlow, the president of the Royal Society, said the award recognised Sir Martin's groundbreaking research. "He is a world leader in mammalian genetics and his research has undoubtedly increased our understanding of human diseases," he said.
From stem cells to 'knockout' mice
Sir Martin Evans is Professor of Mammalian Genetics at Cardiff University and a leading authority on embryonic stem cells, the cells of the early embryo that can develop into any of specialised tissues of the body. Sir Martin was the first person to isolate stem cells – the vital cells with the power to become anything from heart muscle to nerves – from early mouse embryos.
Born in 1941, he read biochemistry at Cambridge in the early 1960s, before going on to do a PhD at University College London where he then taught in the Anatomy and Embryology Department.
Sir Martin,66, demonstrated how to eliminate a functioning gene from an embryonic stem cell of a mouse, which could then be used to create a living mouse with that gene defect.
The first seminal paper on his findings was published in Nature in 1981, in which Sir Martin pointed out that embryonic stem cells might be genetically modified to create mice that could be used as models of human diseases.
By the end of the 1980s, his work had been merged with that of Mario Capecchi and Oliver Smithies to create "knockout" GM mice that had had targeted genes eliminated.
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