Miraculous tales of people coming back from the dead always make good headlines. Like the story of Canadian toddler Erika Nordby, who wandered outside at night in sub-zero conditions and was later found by her mother, almost frozen solid. Despite the fact that she was pronounced clinically dead — her heart had stopped beating for two hours and her temperature had dropped to 16C from the normal 37C — Erika made a full recovery.
But the tales also fascinate scientists. Understanding how people can defy death has big implications for medical care: let doctors put severely ill patients in a state of, in essence, hibernation and you buy them the extra time they might need to work out the best way to treat them.
Now that goal is a step closer. By successfully inducing a state of reversible hibernation in mice, scientists have managed to make a mammal hibernate on demand for the very first time.
Mark Roth of the Fred Hutchinson Cancer Research Centre, in Seattle, led the work and reports his results in the journal Science on Friday. ”We think this may be a latent ability all mammals have — potentially even humans — and we’re just harnessing it and turning it on and off, inducing a state of hibernation on demand,” he said.
When an animal hibernates, the activity of cells in its body slows down nearly to a standstill and the amount of oxygen it needs to survive plummets.
”Manipulating this metabolic mechanism for clinical benefit potentially could revolutionise treatment for a host of human ills related to ischemia, or damage to living tissue from lack of oxygen,” said Roth.
In his experiments, Roth and his colleagues knocked mice out by making them inhale air laced with hydrogen sulphide, a chemical produced in humans and other animals which is thought to help regulate body temperature and metabolic activity. The mice were kept in a hibernation-like state for up to six hours before being returned to normal. During this time, the mice stopped moving and appeared to lose consciousness. Their breathing almost stopped and their core temperatures fell from 37C to as low as 11C.
”We have, on demand, reversibly demonstrated the widest range of metabolic flexibility that anyone has ever seen in a non-hibernating animal,” Roth said.
Hydrogen sulphide is a type of chemical known as an oxygen mimetic. These compounds are similar to oxygen at the molecular level and so bind to many of the same receptors. As a result, they compete for and interfere with the body’s ability to use oxygen for energy production. Roth believes that this interference with normal bodily functions is what caused the mice to hibernate.
”The cool thing about this gas we’re using, hydrogen sulphide, is that it isn’t something manufactured that we’re taking down from a shelf,” said Roth. ”It’s simply an agent that all of us make in our bodies all the time to buffer our metabolic flexibility. It’s what allows our core temperature to stay at 37C, regardless of whether we’re in Alaska or Tahiti.”
If Roth can reproduce hibernation in larger animals, he predicts that the first use of the technology in humans might involve helping people survive life-threatening injuries while in transit to hospital.
”Here’s a patient group, quite commonly found in emergency rooms, who would do well if they could just have their core body temperature taken down in order to buy them time until the pathology reports come back and they can get on the right treatment,” Roth said. ”It will change the way medicine is practised, because we will, in short, be able to buy patients time.”
Hani Gabra, a professor of cancer medicine at Imperial College, London, said that Roth’s work was important for delicate surgery. ”If you have to put the patient on the table for a really long time, organs get damaged. By slowing that process down, you can do more complicated operations for longer,” he said.
Another use of Roth’s technology in humans would be to allow cancer patients to tolerate larger doses of radiation without damaging healthy tissue.
Cancer cells are not dependent on oxygen to grow and, as a result, are more resistant to radiotherapy than surrounding healthy cells. Temporarily removing oxygen dependence in healthy cells could make them a less vulnerable target for radiation and chemotherapy.
”Right now in most forms of cancer treatment we’re killing off the normal cells long before we’re killing off the tumour cells. By inducing metabolic hibernation in healthy tissue we’d at least level the playing field,” said Roth.
Roth’s technique could also be used to extend the time that organs and tissues could be preserved outside the body before being used for transplantation.
Only the slow survive
Hibernation is a survival strategy for animals in environments where food is scarce or just difficult to find during the winter. It allows the animal to slow down its metabolism and use its energy reserves at a slower rate
The European Space Agency is investigating hibernation mechanisms for use on astronauts. Last year, University of Verona researchers found that injecting an opioid-like substance called Dadle into squirrels made them hibernate out of season. It also seems to send cultures of human cells to sleep
Researchers in Boston are examining the brains of hibernating animals. While asleep, the animals’ brains receive much less oxygen than normal. Understanding this could lead to a better understanding of stroke in humans
At the University of Wisconsin, scientists are studying how squirrels can absorb nutrients when, after several months of hibernation, their digestive systems are almost withered away. They hope to better treat human digestive problems – Guardian Unlimited Â