Military scientists to study regrowth of limbs

The natural regeneration of limbs, which has fascinated scientists for more than 200 years, is seen as possible if the secrets of a similar process in amphibians can be deciphered.

The military research has been spurred by the need for potential treatments for the increasing numbers of soldiers with disfiguring injuries.

However, scientists who have long grappled with the problem believe the cloning of Dolly the sheep in 1996 and the first stem cell lines two years later have taken them significantly closer to their goal.

The United States’ Defence Advanced Research Projects Agency (DARPA) is spearheading an initial 250,000 research project, codenamed ReGenesis, to investigate the potential of such work.

Dr Brett Giroir, the deputy director of DARPA’s defence sciences office, said the ability to regrow severed limbs could follow on from studies into accelerating the healing of wounds and burns.

He told a conference in California last month: "This ability to regenerate limbs is present in many species, and even humans can regenerate a normal liver after removing as much as 90 per cent of it during surgery.

"So why can’t this regenerative capability be available for human limbs or the brain and spinal cord?"

While flatworms, sea squirts, fish and amphibians can regrow internal organs and even entire limbs to varying extents, humans can fully regenerate only a very few tissues and organs, including the liver, the blood, and the outermost skin layer.

As children, humans can renew fingertips from the base of the nail upwards. But some scientists believe that growing a new finger could ultimately prove to be as simple as taking a pill, applying a drug-coated bandage or spraying liquid on to a freshly-damaged stump.

"This is doable - I believe it is inevitable that we will regenerate an entire human limb," Dr Ellen Heber-Katz, a biologist at the Wistar Institute in Philadelphia, told the Los Angeles Times.

The science behind the research dates back to 1768, when Lazzaro Spallanzani, an Italian monk, noted that amphibians could regrow their body parts.

One hundred years later, August Weismann, a German biologist, suggested that "ids" - or genes - provided the information which directed the body’s development.

He thought these progressively worked outwards, so cells at the elbow could construct a forearm, hand and fingers. In this way, he believed a stump should contain sufficient information for regrowing an arm or leg.

A further breakthrough came in 1976 when a group of American biologists found that when a salamander’s leg was amputated, the nascent limb which started to grow in its place would prompt other limbs to grow on the amphibian’s body if it was transplanted elsewhere.

However, some claim the science was transformed by the arrival of the world’s most famous sheep, at the Roslin Institute in Midlothian.

"Dolly was the ‘Aha!’ moment," Dr Gerald Schatten, a developmental biologist at the University of Pittsburgh, told the LA Times. "Most medical research viewed salamander regeneration as esoteric, but Dolly has changed the entire thinking about the plasticity of mammals, including humans."

The emergence of stem cells was seen as a further key step, since these offered the possibility of regenerating any other type of cell in the body.

However, researchers are still trying to establish the genetic signals which trigger the first steps towards regeneration.

Dr David Gardiner, a professor of developmental cell biology at the University of California at Irvine, who is experimenting with salamanders, believes there is a "signal and response" when wounds occur. Under this theory, when tissues are damaged in an amputation, cells at the site release signals to call in reinforcements.

Dr Gardiner is convinced that limb regrowth can be achieved because it would follow a similar process that is involved in a human embryo developing arms and legs for the first time.

But other scientists are sceptical about whether such research will ever lead to complete limbs being regrown.

Dr Bruce Carlson, of the University of Michigan, and a leading figure in regeneration research, believes the human body grows scars rather than new limbs to prevent it bleeding to death - and there is good reason for this natural defence mechanism.

Dr Jeremy Brockes, of the department of biochemistry at University College, is only marginally less sceptical.

He said: "The idea that you could make a complex structure like a limb seems at present quite fanciful."

However, he added: "I genuinely believe it is too difficult to say if it is impossible. There is no clear reason why, in principle, it should not happen."