Is suspended animation possible?
Erica Nordby, a toddler in Edmonton Canada had wandered out alone into the frigid night. Before she was resuscitated her heart had stopped beating for two hours and her body temperature had dropped to 61 degrees Fahrenheit. She was brought back to life and has no lasting effects from the experience.
In October 2006, a Japanese man, Mitsutaka Uchikoshi, fell asleep on a snowy mountain and was found unconscious by rescuers 23 days later; doctors who treated him believed his temperature had fallen to 71 degrees Fahrenheit during that period.
Medical science defines hypothermia as being present within an organism when it’s temperature drops to a point at which normal functions are impaired. Typically, hypothermia results in a decrease in metabolism and cellular activity ultimately causing cell death. In addition, there is a significant decrease in blood flow and oxygen levels which causes the muscles, organs and brain to malfunction.
Chilling stories like these intrigued Dr. Mark Roth, an investigator at the Fred Hutchinson Cancer Research Center. After reading accounts of people being revived after long periods in the cold, he became interested in the idea that humans may have metabolic flexibility and be able to decrease their respiration and heartbeat and, in effect, “turn themselves off” in response to physical or environmental stress. These stories may provide clues about our capacity to briefly suspend our vital functions when environmental conditions get rough.
Metabolic flexibility has been around for many years and is observed in mammals that hibernate. During hibernation, there is a decrease in respiration, heart rate and body temperature allowing mammals to survive the cold winter and conserve energy sources.
Additionally, many invertebrates can hibernate for days, months, and even years before reanimating.
Roth was interested in harnessing the effect that cold had on the ability of humans to ‘turn themselves off’ and then reanimate.
Art of hibernation on-demand
After watching a documentary about underground caves on PBS, Roth got an idea about how to induce metabolic flexibility in humans. The television show explained how cave explorers risk encountering the gas hydrogen sulfide, which in high concentrations can immediately render a person unconscious.
Hydrogen sulfide is toxic flammable gas found not only in caves but is produced by volcanoes, hot springs, and bacterial break down of organic matter in swamps and sewers. One of its most notable features is the foul odor of rotten eggs.
Hydrogen sulfide binds with iron in cytochrome enzymes, disrupting a critical step in a process called oxidative phosphorylation, in which oxygen is burned to produce energy in the form of a substance called ATP. By blocking oxygen from binding to the iron, hydrogen sulfide stops cellular respiration and energy production completely. When energy production is inhibited, body temperature and metabolic rate are severely reduced.
Enzymes exist in the body that can detoxify hydrogen sulfide by oxidation to (harmless) sulfate. As a result, low levels of sulfide may be tolerated indefinitely. However, at higher levels it can poison several systems in the body although the nervous system is the most affected.
How did Roth investigate his theory?
Roth hypothesized that perhaps he could prevent death in low oxygen situations by adding agents such as hydrogen sulfide that decrease metabolic activity by inhibiting oxygen utilization and induce suspended animation. Suspended animation refers to the state where all observable life processes are stopped but the animal can later resume its normal function.
The Lazarus effect
The first preliminary experiment Roth carried out was to measure the development of zebrafish embryos under anoxic conditions in the absence of oxygen. He discovered that their development came to a halt and the heart was shut down. He found that the embryos could survive for 24 hours and then resume normal development after re-exposure to oxygen.
These dangerously low levels of oxygen appear to kill the animals but they recover later. Roth notes that a similar ‘Lazarus effect’ has been observed in patients such as those mentioned above who have been pronounced dead after exposure to extreme cold.
When the oxygen levels are too low for respiration but high enough to allow metabolic activity, damage occurs because the cells continue to struggle to live. Under these conditions, seizures, cell death, coma and finally death can occur.
However, decreasing the oxygen levels significantly stops all metabolic activity and the animals enter a state of suspended animation.
Roth then decided to try low doses of the gas to induce suspended animation in mice. He found that he could reversibly reduce the metabolic rate of mice by first exposing them to 80 parts per million of hydrogen sulfide and then exposing them to low oxygen.
In just a matter of minutes, mice entered into what is called a “hibernation-like” state, where their core temperature was reduced to 11 degrees and their respiration dropped from the normal 120 breaths per minute to 10 or less breaths per minute.
In his preliminary mammal experiments, Roth kept the animals in this state for 6 hours and they recovered completely. After the gas was removed, normal metabolic function and activity resumed. In both of these studies, he found discrete and lethal oxygen levels exist just above the oxygen level that enables suspended animation.
Uses for suspended animation
Reduced levels of oxygen supply specifically, can be a major cause of cellular and tissue damage in donor organs and in the bodies of individuals that have suffered severe blood loss or blood flow obstruction in such cases as strokes or heart attacks.
In cases such as these, restoring an adequate oxygen supply is not always easy. In the future, agents such as hydrogen sulfide that alter the metabolic rate of mammals by reducing the need for oxygen could prevent tissue damage and death in stroke or heart attack victims, preserve transplantable organs for longer and buy time for human trauma patients.
In addition, exposure to hydrogen sulfide may improve cancer treatment by allowing patients to tolerate higher radiation doses without damaging healthy cells. Cancer cells aren’t dependent on oxygen to grow and are therefore more resistant to radiation than surrounding healthy cells, which need oxygen to live.
Roth hypothesizes that temporarily reducing oxygen consumption in healthy cells could make them a less-vulnerable target for radiation and chemotherapy and thus spare normal tissue during high-dose cancer therapy.
This work could also be used to put astronauts in suspended animation on long space flights thereby decreasing the need for food and oxygen.
The Future of Suspended Animation
Dr. Mark Roth’s discovery of this novel way of inducing reversible metabolic hibernation has sparked interest in the idea of suspended animation. Based on the stories of individuals reviving after being in a hypothermic state, researchers in other institutions hypothesized that significantly decreasing body temperature induces suspended animation. However, after carrying out hypothermic experiments, they discovered that this can only be done for a short amount of time and even then, there is a risk of tissue and brain damage.
Chemically induced suspended animation seems to be the method of choice to achieve a state of metabolic hibernation. Researchers at Massachusetts General Hospital have repeated the hydrogen sulfide studies of Dr. Roth and have obtained the same results. Thus far, no ill side effects have been observed Further development of this method could have a tremendous impact in the fields of critical care, neurological, surgical and organ transplant medicine.