Torpor on Demand

METABOLISM RESEARCH

Hydrogen sulfide, a gas that is lethal at high concentrations, has been found--at lower levels--to induce a state similar to suspended animation in mice (Science 2005, 308, 518).

If the finding turns out to be applicable to humans, the researchers believe it could ultimately lead to better ways to treat cancer, prevent injury or death from insufficient blood supply to organs and tissues, and rapidly lower the core body temperature of patients with dangerously high fevers.

When Mark B. Roth of Seattle's Fred Hutchinson Cancer Research Center and coworkers exposed mice to H₂S at 80 ppm, they found that the animals' O₂ consumption and CO₂ output dropped dramatically within five minutes. If left in this environment for six hours, the metabolic rate of the mice plummeted by about 90%, followed by a major drop in core body temperature.

Once the H₂S was removed, the mice returned to normal and showed no signs of any ill effects, according to the researchers.

The mice were put into a hibernation-like state where cellular activity slows to a near standstill, Roth says. In this state, the animals' need for oxygen is greatly reduced. If this state could be duplicated in humans, he believes, it could buy time for critically ill patients awaiting organ transplants or other surgical procedures. For example, depressing metabolic activity might extend the period that organs and tissues could be preserved outside the body prior to transplantation.

The mechanism by which H₂S acts on the metabolism isn't completely understood. But H₂S is known to disrupt a critical step in oxidative phosphorylation, the process by which the cell generates metabolic energy.

Still, no one knows whether H₂S will have the same metabolism-depressing effect in humans. Physiologist Rui Wang of Lakehead University, in Thunder Bay, Ontario, who studies the biology of H₂S, believes it's far-fetched "to extrapolate this discovery to inducing human hibernation."

Roth stresses that the work is at an early stage and that his group next must show that some medical benefit can be garnered from putting a mouse into this hypometabolic state.