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A step toward a time-buying strategy to benefit humans
Scripps Howard News Service


April 24, 2005

Scientists have taken a key step toward inducing "hibernation on demand" in humans at risk of injury or even death from insufficient blood supply and oxygen to vital organs and tissues.

Researchers at the Fred Hutchinson Cancer Research Center in Seattle report Friday in the journal Science that lab mice entered a "suspended animation-like state" when exposed to a low concentration of hydrogen sulfide.

Within five minutes of breathing normal room air laced with 80 parts per million of the gas - which has the signature rotten-egg smell when released from sewers and petroleum refining - the mice's oxygen consumption dropped by half and carbon-dioxide production fell by two-thirds.

The rodents stopped moving, appeared to lose consciousness and respiration dropped from a normal 120 breaths per minute to fewer than 10 breaths per minute. Additionally, the core body temperature fell from 98.6 degrees Fahrenheit to as low as 51.8 degrees.

Normal function and activity levels resumed when the hydrogen sulfide was removed from the chamber after hibernation had gone on for up to six hours.

"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," said Mark Roth, lead investigator for the study and an affiliate professor of biochemistry at the University of Washington School of Medicine.

Roth and colleagues have already shown they can artificially suspend activity and then re-animate creatures such as yeast, worms and the embryos of fruit flies and zebra fish.

If the slowdown of metabolic activity and demand for oxygen can be replicated in humans, it could help buy time for critically ill patients awaiting surgery or organ transplants or those undergoing cancer treatment.

In hospitals and on the battlefield, applications could include treating people suffering from severe blood loss, hypothermia, severe fever, heart attack and stroke.

The technique also might be used in cancer treatment. Roth explained that cancer cells don't require oxygen to grow, making it harder to eradicate them with radiation or chemotherapy without damaging surrounding healthy cells that do need oxygen.

Roth argues that if tissues surrounding tumors could temporarily lose the dependence on oxygen, they'd suffer less collateral damage from therapy. "Right now, in most forms of cancer treatment, we're killing off the normal cells long before we're killing off the tumor cells," he said. "By inducing metabolic hibernation in healthy tissue, we'd at least level the playing field."

Slowing metabolism might also be used to extend the amount of time organs and tissues could be preserved outside the body before they're transplanted, and also help speed the healing of wounds in some patients, such as diabetics.

Humans and other animals produce hydrogen sulfide naturally in small quantities to help regulate cell metabolism. "It's what allows our core temperature to stay at 98.6 degrees, regardless of whether we're in Alaska or Tahiti," Roth said. "It isn't something manufactured that we're taking down from a shelf."

The compound is so similar to oxygen at the molecular level that it binds to cell receptors for oxygen and inhibits the ability to use oxygen for energy production, slowing metabolism.

But exposure to hydrogen-sulfide concentrations greater than 500 parts per million can cause loss of consciousness and even death in humans, and exposure to lower concentrations can cause irritation to the eyes, nose and throat. So getting the dose right for medical treatment will be essential.

The idea of putting a human or an organ into an oxygen-free limbo and then reversing the process at will may sound like science fiction. However, researchers point to documented cases of people being in hibernation-like states for an hour or two due to hypothermia and suffering no long-term ill effects.

Roth believes that if tests on larger, more complex animals go well, the first clinical trials of the technology could come on humans in about five years.


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