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State of Hibernation Is Induced in Mice

Process Would Have Many Medical Uses

By Rob Stein
Washington Post Staff Writer
Friday, April 22, 2005; Page A09

Scientists have induced a state close to suspended animation in a mammal for the first time, a long-sought achievement that could lead to a host of medical advances for people.

By exposing mice to hydrogen sulfide gas, the researchers managed to place the animals into a condition equivalent to hibernation, which could be quickly reversed without apparently harming the creatures simply by letting them breathe fresh air.

Mark Roth sees "tremendous value for medicine." (File Photo)

If researchers confirm the safety of the approach and show it works the same way in people, it would achieve a goal that has remained in the realm of science fiction despite decades of efforts.

"This could have tremendous value for medicine," said Mark B. Roth of the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle, who led the research reported in today's issue of the journal Science. "This is a very promising means by which we might buy time for ourselves when we need it most."

Slowing metabolic functions to a near standstill preserves organs and other tissues. That could, for example, give critically ill patients awaiting organ transplants more time, keep patients suffering severe blood loss from car accidents or gunshot wounds alive long enough to get transfusions and surgery, minimize damage from heart attacks and strokes, and help minimize the side effects of cancer chemotherapy and radiation.

"It's pretty exciting -- almost to the point of being hard to believe," said Philip E. Bickler, an anesthesiologist who has been doing research in this area at the University of California at San Francisco for 15 years. "This idea of suspended animation has been around for at least 50 years. It's just never panned out before. This could have huge implications."

Scientists have been able to induce such states in primitive organisms such as yeast, worms, fruit flies and zebra fish, but never before in a mammal. Many animals can slow their metabolism naturally when they go into hibernation, enabling them to survive long periods when the weather is inhospitable and food and water are scarce.

Researchers have tested a variety of approaches designed to mimic that state in non-hibernating species, including people, without much success. Doctors cool some stroke victims to minimize damage to their brains and some surgical patients to minimize bleeding, but the approach is difficult, can be dangerous and is of limited use.

As a result, suspended animation has remained largely the stuff of science fiction books and movies about space travelers being frozen to survive long journeys or terminally ill people hibernating until a cure could be found.

But real-life scientific interest in the field has remained intense. The Defense Department, for example, which helps fund Roth's work, hopes to find better ways to protect soldiers until they can be evacuated from the battlefield.

In the new work, Roth and his colleagues placed mice that do not naturally hibernate in a chamber filled with normal air laced with hydrogen sulfide. The gas is produced by humans and other creatures as part of the body's system for regulating energy. In high doses it can be toxic, but the researchers used very low levels -- 80 parts per million.

Within five minutes of being placed in the chamber with the gas, the mice stopped moving and lost consciousness. Their breathing dropped from a normal rate of about 120 breaths per minute to fewer than 10. Their oxygen consumption plummeted, and their body temperatures fell from 98.6 degrees Fahrenheit to a low of 51.8.

Eventually, their metabolic rate slowed by about 90 percent, coming virtually to a halt, the researchers reported.

After six hours, the mice were removed from the chamber and placed in a room with regular air. They quickly began to stir, and their metabolic functions began slowly to recover. Within two hours, they were back to normal.

Previous research has shown that the levels of hydrogen sulfide used in the experiment were safe for mice, Roth said. But the researchers subjected the animals to a raft of behavioral and functional tests to see whether there were any detrimental effects. They found none.

"We are, in essence, temporarily converting mice from warm-blooded to cold-blooded creatures, which is exactly the same thing that happens naturally when mammals hibernate," Roth said. "We think this may be a latent ability that all mammals have -- potentially even humans -- and we're just harnessing it and turning it on and off, inducing a state of hibernation on demand."

In addition to the potential medical applications, the findings provide important new insights into the fundamental mechanisms involved in regulating metabolism, experts said.

"People have been trying to understand how animals can induce a metabolically reduced state like this for a long time," said Hannah Carey, a physiologist at the University of Wisconsin at Madison School of Veterinary Medicine. "This is pretty exciting."

Roth and other researchers cautioned that much more research is needed to verify that the approach is safe, and they stressed that it would have to be tested on other species before it is even attempted in people. But they were optimistic.

"It's got great potential," said Samuel A. Tisherman, associate director of the University of Pittsburgh's Safar Center for Resuscitation Research. "All they've done so far is a mouse, so there's a lot more they have to do."

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