Mice Forced Into Hibernation

It sounds like science fiction, yet an experiment in which mice were forced into hibernation and then revived with no apparent ill effects, might ultimately lead to new ways to treat the critically ill.

Consider it hibernation-on-demand, a way to drastically reduce the amount of oxygen needed to survive, researchers from Seattle's Fred Hutchinson Cancer Research Center report Thursday in the journal Science.

It works, essentially, like hypothermia.

Recall those miraculous cases of people who fall into icy ponds and appear dead but recover after they're warmed up? The extreme cold preserves their brain cells from the certain death that would otherwise quickly follow oxygen deprivation.

Following that logic, doctors now sometimes use ice to chill stroke victims in hopes of minimizing the damage to their brains.

Chilling might help other illnesses, too, such as by buying time for surgeons to stop a trauma victim's hemorrhaging. But inducing hypothermia is difficult and can take time that patients may not have, so scientists are hunting ways to lower body temperature more effectively from the inside-out.

The new experiment does that in a novel way, by using a small amount of hydrogen sulfide gas to force the mice into a state of hibernation for six hours.

"We wonder whether we've stumbled on a way to access this quiescent state in a way that could be beneficial for medicine," said lead researcher Mark Roth, a cell biologist at Fred Hutchinson. "It's engaging metabolic flexibility, which heretofore was not widely recognized as something that exists."

Within minutes of inhaling the gas, the mice appeared unconscious. Their body temperature plummeted from the normal 98 degrees down to 59 degrees and their respiration slowed to fewer than 10 breaths a minute, down from a normal 120 breaths a minute, Roth reported.

Overall, their metabolic rate dropped by 90 percent - meaning normal cellular activity slowed to almost a standstill, thus reducing the need for oxygen.

Fresh air revived the mice, and testing uncovered no differences in behavior or functional ability between the treated mice and untreated ones, the study concluded.

The research is "very intriguing," said Dr. David Sachs, a Harvard University transplant specialist, who said it might point to ways to help donated organs survive longer before transplant.

"Being able to decrease the metabolic rate by, they're saying, 90 percent and have an animal that's not injured by it is rather remarkable," he added.

The next step is to see whether large animals can be pushed into this hibernating state, too, and if doing so while an animal is ill actually helps.

"Certainly what happens in mice may not happen in larger animals," cautioned Dr. Samuel A. Tisherman, a critical-care specialist and associate director of the University of Pittsburgh's Safar Center for Resuscitation Research. He induces hypothermia by infusing animals with large amounts of cold salt water, but is considering collaborating with Roth to see if the hydrogen sulfide might help.

"It's got great potential," stressed Tisherman. "It conceivably could help tremendously to, specifically, help preserve organs but also help induce the hypothermia" faster.

Hydrogen sulfide, a component in sewer gas, is known to be highly toxic. But the body naturally produces some hydrogen sulfide, which helps regulate normal body temperature by adjusting how much oxygen cells burn to produce energy, Roth explained. He said the experiment used amounts considered to be safe.

By Lauran Neergaard