Photo courtesy of the John D. and Catherine T. MacArthur Foundation
New findings from the laboratory of cell biologist Dr. Mark Roth of the Basic Sciences Division may help explain how some people who appear to freeze to death, with no heart rate or respiration for extended periods, can be brought back to life with no long-term negative health consequences.
Reporting online ahead of the July 1 print issue of Molecular Biology of the Cell, Roth and colleagues show that two widely divergent model organisms—yeast and nematodes (worms)—can survive hypothermia if they are first put into a state of suspended animation by means of anoxia, or extreme oxygen deprivation.
Benefits of anoxia-induced suspended animation
The researchers found that under normal conditions, yeast and nematode embryos cannot survive extreme cold. After 24 hours of exposure to temperatures just above freezing, 99 percent of the creatures expire. In contrast, if the organisms are first deprived of oxygen and thus enter a state of anoxia-induced suspended animation, 66 percent of the yeast and 97 percent of the nematode embryos will survive the cold. Once normal growth conditions are resumed—upon rewarming and reintroduction of oxygen—the organisms will reanimate and go on to live a normal lifespan.
A better understanding of the potentially beneficial, symbiotic relationship between low oxygen and low temperatures may one day lead to the development of improved techniques for extending the shelf life of human organs for transplantation, Roth said.
“We have found that extension of survival limits in the cold is possible if oxygen consumption is first diminished,” he said. “Our experiments in yeast and nematodes suggest that organs may last longer outside the body if their oxygen consumption is first reduced before they are made cold.”
Roth’s laboratory studies the potential clinical benefits of metabolic flexibility—from anoxia-induced reversible suspended animation to metabolic hibernation brought on by exposure to agents such as hydrogen sulfide. The ultimate goal of this work is to find ways to temporarily lower metabolism—like dialing down a dimmer switch on a lamp—as a means to “buy time” for patients in trauma situations, such as victims of heart attack or blood-loss injury, by reducing their need for oxygen until definitive medical care can be given.
Halting the cell cycle
The mechanism by which anoxia-induced suspended animation protects against extreme cold has to do with preventing the cascade of events that lead to biological instability and, ultimately, death. For example, suspended animation preserves the integrity of cell-cycle control by preventing an organism’s cells from dividing in an error-prone fashion. During suspended animation, the cell cycle is reversibly halted. Upon reanimation, the cycle resumes as normal.
“When an organism is suspended its biological processes cannot do anything wrong,” Roth said. “Under conditions of extreme cold, sometimes that is the correct thing to be doing; when you can’t do it right, don’t do it at all.”
The first author of the paper, Dr. Kin Chan, formerly a postdoctoral research associate in the Roth Lab, is now with the Laboratory of Molecular Genetics in the National Institute of Environmental Health Sciences at the National Institutes of Health.
The NIH and the National Science Foundation funded this research.