Their discoveries have led to generations of genetically modified mice with eccentric names such as Methuselah, Frantic or P53.

Yesterday the three scientists responsible shared the Nobel Prize for Medicine for the creation of “knockout” mice, which have proved a fantastic tool for investigating the purpose and behaviour of genes.

Sir Martin Evans, of Cardiff University, shared the £755,000 prize with Oliver Smithies, born in Halifax but resident in North America for more than half a century, and Mario Capecchi, another naturalised American.

Researchers depend on mice with specific genes silenced to decipher disease, devise treatments and explore the mysteries of the genetic code.

It had been a “grand, groundbreaking achievement”, said Steve Brown, the head of the Mammalian Genetics Unit of the Medical Research Council.

“Most of our profound understanding of how genes cause disease in humans has come by identifying particular genes in the mouse, knocking them out, and then looking at what disease develops in the mouse and how it develops,” the professor said. “Without this toolkit, we would be considerably hampered.”

The three scientists pioneered the technique in the 1980s, devising techniques for removing a functioning gene from the mouse’s genetic code and replacing it with a flawed counterpart to replicate human disease.

Knockout mice have been used as a model for various cancers, heart disease, diabetes, Parkinson’s disease, Alzheimer’s and other conditions.

Methuselah mice, which have extraordinary longevity, are helping to find the keys to ageing, while Frantic mice are shedding light on the genetic roots of anxiety. Others carry the name of the disease-causing gene, such as the P53 cancer gene. The Nobel jury said: “Ongoing international efforts will make knockout mice for all genes available within the near future.”

The chief contribution of Sir Martin, 66, was to use special cells extracted from early-stage mouse embryos to deliver the modified genes. These cells later became known as embryonic stem cells, now being investigated as potential treatments for disease thanks to their ability to develop into different kinds of tissue. Sir Martin is widely credited with their discovery.

His experiments showed that stem cells could be genetically altered in the laboratory, then injected into mouse embryos to create offspring with changes to their DNA that would be passed on to future generations.

The contribution of Dr Capecchi and Dr Smithies was to target genes through “homologous recombination” — “homologous” means that the introduced DNA sequence lines up with its mirror target sequence in the mouse chromosome, while “recombination” means the incoming and target sequences break and then rejoin.

In 1989, the two lines of work came together with the first reports of homologous recombination in embryonic stem cells being used to generate knockout mice. Gene targeting has now developed to the point where it is possible to introduce inactivated genes that can be “switched on” at specific times or in particular cells or organs.

Lord Rees of Ludlow, the President of the Royal Society, said: “This is a fitting recognition of Sir Martin’s ground-breaking research on embryonic stem cells. He is a world leader in mammalian genetics and his research has undoubtedly increased our understanding of human diseases.”

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