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Frozen in Time: Gas puts mice metabolically on ice

Christen Brownlee

Putting people into a state of suspended animation is a mainstay of science fiction, but a new study may have brought the idea closer to reality. By exposing mice to low concentrations of hydrogen sulfide gas in air, researchers slowed the animals' metabolic rate to a near standstill with no apparent ill effects.

Many animals undergo periods of extreme metabolic slowdown, or torpor, in which heart rate drops, breathing slows, and body temperature plunges. For some organisms, such as several species of hummingbirds, this drop in metabolic rate is a daily event. Other animals, such as bears, experience a seasonal slowdown for months while they hibernate.

Researchers have predicted numerous benefits of inducing torpor in people—for example, preventing further damage after a stroke or heart attack by slowing the body's often-harmful response, or putting a patient into a metabolically suspended state while he or she awaits a vital-organ transplant. However, scientists have had few successes in slowing metabolism and then safely reviving mammals that don't naturally undergo torpor.

After using hydrogen sulfide to successfully induce torporlike states in several non-mammalian species, such as yeast, worms, and flies, Mark Roth and his colleagues at the Fred Hutchinson Cancer Research Center in Seattle attempted this feat in common lab mice (Mus musculus), which don't normally undergo torpor.

By administering room air laced with 80 parts-per-million of hydrogen sulfide, a noxious gas that smells like rotten eggs, the researchers induced mice to enter a hibernation-like state. Within minutes of breathing the gas in an enclosed chamber, the mice stopped moving and appeared to lose consciousness. Their respiration gradually dropped over the next 6 hours from the normal 120 breaths per minute to fewer than 10 breaths per minute. Moreover, the rodents' body temperatures dropped from the normal 37°C to as low as 11°C, depending on the air temperature within the chamber.

After the researchers shut off the gas and pumped in normal room air, the mice progressively regained their normal activity levels. A battery of behavioral and functional tests showed no difference between mice that had been metabolically suspended and those that hadn't.

Roth's team reports its findings in the April 22 Science.

Inducing a torporlike state with hydrogen sulfide may have been successful because the gas competes with oxygen in mitochondria, cells' power-generating machinery, says Roth. While processing hydrogen sulfide instead of oxygen, the cells' metabolic activity gradually slows, he hypothesizes.

Since mammalian cells normally produce some hydrogen sulfide, the results could indicate how hibernators and other animals naturally enter torpor, says Hannah Carey, a researcher at the University of Wisconsin–Madison who studies hibernating ground squirrels.

Roth notes that experiments with a variety of mammals are needed to determine whether gas-induced torpor will be feasible in people. "We think this may be a latent ability that all mammals have," he says.

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Letters:

It seems that one of the intriguing potential beneficial applications of hydrogen sulfide-induced torpor would emerge if it turns out that cancer cells are less sensitive to the gas than healthy cells are. If we could turn down the metabolic activity of normal tissue, reducing its sensitivity to chemotherapeutic drugs, while the cancer cells remained vulnerable, chemotherapy would simultaneously become less toxic and more effective.

Starfinder Stanley
Oakland, CA

If this ability is indeed an ancient adaptation, it might explain how the precursors of small mammals, reptiles, and birds could have survived the Cretaceous and Permian extinctions. Hydrogen sulfide would have been a fairly ubiquitous by-product of the massive die-off of vegetation.

James M. Kelly
East Sandwich, MA

References:

Blackstone, E., M. Morrison, and M.B. Roth. 2005. H2S induces a suspended animation-like state in mice. Science 308(April 22):518. Abstract.

Further Readings:

Carey, H.V., et al. 2003. Mammalian hibernation: Cellular and molecular responses to depressed metabolism and low temperature. Physiological Reviews 83(October):1153–1181. Abstract.

Nystul, T.G., and M.B. Roth. 2004. Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans. Proceedings of the National Academy of Sciences 101(June 15):9133–9136. Abstract.

A version of this article written for younger readers is available at Science News for Kids.

Sources:

Hannah Carey
Department of Comparative Biosciences
School of Veterinary Medicine
University of Wisconsin, Madison
2015 Linden Drive West
Madison, WI 53706

Mark B. Roth
Division of Basic Sciences
Fred Hutchinson Cancer Research Center
P.O. Box 19024
Seattle, WA 98109-1024


From Science News, Volume 167, No. 17, April 23, 2005, p. 261.