The Geniuses Of Regeneration

Paid to think out of the box, technologists at the Defense Dept. toy with an outlandish vision of the future soldier . In addition to being a high-tech fighting machine, this soldier has awesome healing powers. If a foot is shot off, this warrior simply pops a pill or applies a spray and voilà! -- the wound seals over and the limb starts to grow back. The Defense Advanced Research Projects Agency (DARPA) is now considering handing out research grants to scientists working on regeneration, in the hope that someone will turn this dream into reality.

With soldiers suffering grievous wounds every day in Iraq, it's no surprise DARPA is thinking about regeneration. And at least a few slender scientific facts give them reason for optimism. Studies in the 1970s showed that children who lose fingertips in accidents can regrow the tip of the digit within a month provided their wounds are not sealed up with flaps of skin -- the de facto treatment in such emergencies.

Yet humans pale in comparison to salamanders. If a human finger is sliced off below the nail line, it won't come back. But when a rowdy 8-year-old pulls off a salamander's leg, an entirely new limb will slowly regrow right out of the stump.

Learning what is behind this incomparable reengineering feat might lead to new ways of thinking about limb regrowth in humans. Scientists at Purdue University, for example, have spent years studying and manipulating faint electrical currents in the skin that appear to regulate regeneration. By inhibiting such a current after amputating a salamander's leg, they can, in effect, flip a switch that shuts down the process of regrowth. The researchers are testing electrical fields on human tissue, hoping to switch on regeneration where it doesn't normally occur. Soon they will publish results of a study in which weak electrical fields helped restore some function to patients with severe spinal-cord injuries. Says Richard Borgens, director of Purdue's Center for Paralysis Research: "This isn't science fiction."

Scientists at Scripps Research Institute in San Diego are taking a different, cell-based approach. When a salamander loses a leg, the cells at the wound site enter a molecular time machine: They transform from, say, muscle or skeletal cells back to "progenitor" cells -- similar to stem cells in their versatility. Then they multiply and differentiate into the cells needed to grow a new leg. In December, Scripps scientists announced that they have created a synthetic molecule, called Reversine, that turns a mouse's muscle cells back into progenitor cells.

The Scripps team is searching for chemicals to induce these precursor cells to grow into specific tissues. Then they must figure out if the results can be applied to humans. If so, at least in principle, a soldier in battle might swallow one pill that would send cells at the wound site into time-machine mode and another to trigger regeneration of lost bone, cartilage, and skin. "We think this is the future," says Sheng Ding, who is leading the Scripps research. If soldiers can discover their inner salamanders, war -- and peace -- will never be the same.

By Arlene Weintraub in Los Angeles

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