BEARS do it. Squirrels do it. But the idea that people might be able to hibernate 鈥� during long space flights, for instance 鈥� belongs in the realm of science fiction. Or does it? Researchers have managed to slow the metabolism of mice to a virtual standstill, effectively placing them in a state of suspended animation.
The work raises the tantalising possibility of inducing the same state in people, which would buy doctors time to patch up critically injured patients. The findings might even help to explain cases of patients coming back to life after being pronounced dead.
Like people, mice do not usually hibernate. But when Mark Roth鈥檚 team at the Fred Hutchinson Cancer Research Center in Seattle exposed mice to just 80 parts per million of hydrogen sulphide 鈥� the highly toxic gas that gives rotten eggs their distinctive pong 鈥� they rapidly entered a state resembling hibernation (Science, vol 308, p 518). The animals鈥� metabolic rates plummeted by 90 per cent, core body temperature fell from the usual 37 掳C to just 15 掳C and they took just two shallow breaths per minute, instead of the usual 150. Once they started breathing normal air again, their metabolism returned to normal.
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So far the team has kept mice in this state for up to 6 hours, with no sign of any harm. 鈥淲e can do it on the same animal every day in a week, and it鈥檚 quite happy,鈥� says Roth.
How much longer mice could be kept in this state is not clear. The 6-hour period was chosen to fit into the working day. 鈥淚 seriously doubt that it will be indefinite because we know the limits for suspended animation in several other animals,鈥� Roth says. 鈥淭hey usually survive for a couple of days at most.鈥�
Roth suspects that hydrogen sulphide, which is also produced naturally in cells, inhibits the production of adenosine triphosphate (ATP), the energy-carrying molecule that fuels cellular processes. Making ATP requires oxygen, which is why cells have such a voracious demand for the gas. Once the demand for oxygen is cut off, cells appear to go into a dormant state. Restoring the normal oxygen supply revives the cell鈥檚 metabolism. 鈥淚f you drop supply but demand stays high, cells are dead,鈥� says Roth. 鈥淏ut if you drop demand, then what do you care if the supply drops?鈥�
Not everyone is convinced that this is the mechanism, however. Phil Bickler, an anaesthetist at the University of California, San Francisco, who describes the results as 鈥渟tunning鈥�, wonders whether the gas depresses metabolism by acting on the hypothalamus, the part of the brain that controls body temperature. 鈥淢aybe it tricks the brain into thinking it鈥檚 too warm, so the animal loses heat by driving metabolism down,鈥� he says.
Bickler also wonders if the mice are not truly hibernating, but instead shut down due to contact with a toxic substance. This is known to happen when mice are exposed to ozone, for example. 鈥淚t might be a generalised stress response,鈥� he suggests.
The dramatic speed of the effect is quite unlike normal hibernation, agrees Gerhard Heldmaier, a hibernation expert at the University of Marburg in Germany. 鈥淪pontaneous metabolic depression in hibernation requires about an hour,鈥� he says. 鈥淏ut the metabolic depression in response to hydrogen sulphide is completed in 3 minutes, indicating it鈥檚 an acute response to a toxin, not a controlled down-regulation.鈥�
鈥淲e can put the same animal into a dormant state for six hours every day in a week, and it鈥檚 quite happy鈥�
For medical applications (see right), how it works matters less than whether it works. Finding out will not be easy, because hydrogen sulphide is so poisonous that it is unlikely the mice experiments will be repeated on people. Accidental exposure to the gas frequently kills workers in the sewage, farming and petrochemical industries. And even if it did work, handling such a toxic gas in an ambulance or hospital would be a practical nightmare. Instead, Roth hopes it will be possible to develop an injectable drug that could be tested on people.
In the meantime, there is the intriguing possibility that the kind of metabolic shutdown observed in mice could explain at least some cases of the Lazarus phenomenon, in which patients come back to life minutes or hours after being declared dead. Roth speculates that cell death requires oxygen, so when concentrations drop below a critical level, the cells do not die but enter a dormant state similar to that induced by hydrogen sulphide. This allows them to recover without damage. But other experts are sceptical. 鈥淚 don鈥檛 buy that,鈥� says Bickler. 鈥淚t鈥檚 too far-fetched.鈥�
