A Brief History of Cryosleep
How scientists are trying to make humans hibernate, and the real science behind one of science fiction's favorite tropes.
Image: Interstellar/Paramount Pictures
Earlier this month, 15 top European scientists, who study a variety of medical disciplines, met at the behest of the European Space Agency to discuss how they might solve the peculiar problem of sending a human to deep space. Well, actually, ESA and NASA believe they might already know what it takes. So, more specifically, the scientists were meeting to discuss how we might purposefully induce a human being to hibernate.
Such a conversation would seem perhaps many decades ahead of its time, until you realize that, in many ways, purposefully lowering a human's body temperature until they pass out is something we already do routinely.
Cryosleep, a process in which an astronaut is put into a state of suspended animation using a drug or a chamber or something very cold, is a common sci fi trope. It's one of the main plot points in 2001: A Space Odyssey. It's how the wormhole-traversing astronauts manage to not age in Interstellar. It's in Aliens and Avatar and it's even shows up in the not-very-good Riddick tetralogy.
The theory is pretty much always the same: Transporting a human into deep space without some sort of Star Wars-esque hyperdrive is long, physically grueling, taxing from a resource perspective, and, not inconsequentially, really boring.
Hollywood's solution to these problems has long been to knock out the astronauts and wake them up later, the thinking being that if you're in a state of suspended animation, you won't need much (if any) food and water, you won't get bored and fight your crew mates, and your body will generally enter a protective state. That's how it works in sci fi. And that's exactly how scientists are hoping it'll work in real life, too.
The term "cryosleep" doesn't refer to any real-life process, real-life medical treatment, or any real-life thing scientists are researching. We most commonly think of "cryonics" as the preservation of a body after someone is dead, in hopes that we'll someday be able to resurrect them or otherwise cure whatever killed them. Cryosleep doesn't refer to that, either. But the sci fi term cryosleep (also commonly called "stasis" or "suspended animation") does closely refer, more or less, to "torpor," a state of unconsciousness achieved by hibernating animals.
And torpor, well, scientists are working on that, for lots of reasons we'll get to shortly. In the meantime, we have a treatment called "therapeutic hypothermia" that approximates at least some of effects of torpor, with scientists rapidly and unrelentingly pushing toward putting humans in a true torpid state, essentially mimicking cryosleep that you commonly see in movies.
Many doctors who use therapeutic hypothermia swear by it, say that they have saved hundreds of lives that would have otherwise have been lost.
But the process isn't that much more complex today than it was thousands of years ago.
Doctors literally cool down patients with ice packs, chilled water pads, cold intravenous saline solutions, or use a product called RhinoChill, in which controlled coolant is inhaled by a patient
For as long as we've been studying medical history, there have been people who have used cold temperatures to attempt to treat dire ailments. While Hippocrates once noted that that "cold is bad for the bones, teeth, nerves, brain, and the spinal cord," he nonetheless is believed to have covered injured soldiers with snow or ice to slow the flow of blood and give their bodies time to heal the wound. A paper published in 2004 by Dutch researcher Kees Polderman about therapeutic uses of hypothermia suggests that "medicinal use of hypothermia was described by the ancient Egyptians in the so-called Ebers Papyrus, and by Hippocrates, Celsus, and Galaenus."
Let's just say medicine wasn't all that great until we finally learned how the body and disease worked—there were some ill-fated attempts to use the cold as medicine in the thousands of intervening years, but few of them had any sort of success. So let's skip forward many hundreds of years to the mid 20th century, when doctors began experimenting with induced hypothermia. In 1945, a researcher named TB Fay published a paper called "Observations on generalized refrigeration in cases of severe cerebral trauma." Fay would purposefully cool down patients with traumatic brain injuries in hopes that swelling would decrease, metabolism would slow down, and their body would eventually recover.
For years, doctors would occasionally attempt to cool patients who were in a dire state, with very mixed results. Remember, the average human's body temperature is 98.6°F (about 37° C); hypothermia can set in when the body's temperature hits 95° F (35° C).
"Patients were generally treated with deep hypothermia (usually <30°C [about 86° F]) for variable periods of time. This was in a time without intensive care facilities, so patients were usually cooled using ice and cold water on the general ward," Polderman wrote. "Some of these studies appeared to show benefits (compared to 'expected outcome' or historical controls), but these benefits were variable and uncertain. This uncertainty regarding efficacy, as well as management problems and the severe side effects associated with hypothermia, led to the discontinuation of this form of treatment."
All chemical reactions occur more slowly at lower temperatures, and this is the general reason why therapeutic hypothermia is supposed to work.
"There are cells in the body that are very sensitive to a lack of oxygen, and if you have a stroke or a cardiac arrest, the body isn't providing that oxygen," Matteo Cerri, a neurophysiologist and hibernation researcher at the University of Bologna in Italy told me. "If you lower the temperature of the brain, the neurons can use what they have for a longer time."
Fay's research was interesting, but few hospitals actually cooled down patients during the latter part of the 20th century. It was a series of accidents that inspired renewed interest among the public in the potential protective effects of being very cold. In 1999, Swedish radiologist Anna Bagenholm was trapped under a layer of ice for 80 minutes after a skiing accident. Her heart stopped for three hours and her core body temperature decreased to 56 degrees. Doctors revived her, and she eventually made a nearly full recovery, save for some minor nerve damage.
This case and subsequent medical research published in 2002 by two teams led to the widespread use of therapeutic hypothermia (which was now called by this name or "targeted temperature management") in patients who had suffered acute cardiac arrest, stroke, or neurological damage.
The American Heart Association was soon recommending therapeutic hypothermia as a treatment for certain ailments, and the 2006 case of Mitsutaka Uchikoshi, a Japanese man who is believed to have survived for 24 days without food and water after his body went into a hypothermic state, further emboldened those who say putting people on ice—in a controlled way—can have positive medical effects.
"There is a conceptual difference in the way hibernation works compared to hypothermia"
Since the early 2000s, doctors have purposefully induced hypothermia in thousands of patients around the world.
But the process is all pretty rudimentary, and recently there have been arguments that it doesn't really work all that well. Doctors literally cool down patients with ice packs, chilled water pads, cold intravenous saline solutions, or use a product called RhinoChill, in which controlled coolant is inhaled by a patient. None of these methods are believed to be better than the other, all are uncomfortable, all are temporary (we can do it for roughly 72 hours, max), all come with potentially severe side effects.
The most important side effect is the fact that those who are in a state of hypothermia tend to shiver.
All the research into therapeutic hypothermia has run adjacent to animal research in the field of "torpor," which most people know as hibernation. New findings in both fields has put the two on a collision course, and something of a scientific consensus: The ability to induce true hibernation is better in just about every sense than putting a bunch of ice packs on a human, which is what we still do in many cases today.
The key difference between therapeutic hypothermia and torpor is the fact that a hibernating body cools itself naturally, while a hypothermic one tries very hard to warm itself back up.
"There is a conceptual difference in the way hibernation works compared to hypothermia," Cerri said. "With hypothermia, you cool down the body of a mammal, which reacts to this cooling and will counteract the positive effect. In hibernation, the body actually cools itself. It doesn't produce any more heat, and it doesn't defend its temperature."
If she or someone else can cause a pig to hibernate, that'd be an astounding result with potentially very important ramifications for the future of humans.
That's why the new goal, for clinicians hoping to use it on Earth and for space agencies, is figuring out a way to make humans go into a totally natural hibernative state. The ideal is something close to the cryosleep you see in sci fi.
"I've heard from clinicians who do this—there are hypothermia trials in stroke patients that aren't working well, and quite a lot of controversy for cardiac arrest use. There was a trial that came out in 2013 that showed no effect in lowering the body temperature from 36 C to 33 C," Kelly Drew, a hibernation researcher at the University of Alaska Fairbanks told me. "A lot of hospitals are abandoning cooling, while a lot had never adopted it in the first place."
When mammals hibernate, their bodies automatically and naturally lower their body temperature, meaning humans would get the beneficial aspects of therapeutic hypothermia (the lowered metabolism, the slowed heart rate, etc), without the terrible side effects (shivering, skin and nerve damage, potential for something to go wrong). In theory, humans would also be able to hibernate for a much longer time than we're able to put someone into a hypothermic state, perhaps weeks or months compared to hours or days.
"Medicine could be buoyed a lot by hibernation. Right now, they just make people cold and don't do it in a coordinated way like an animal does," Drew said. "When an animal goes into hibernation, blood pressure management is well-integrated into whatever is going on. The animal has complete control. Right now, that integrated system is lacking [with therapeutic hypothermia]."
Drew said that doctors often inhibit shivering in hypothermic patients using powerful narcotics and intubating patients, and even those tactics aren't always effective: "Hibernation really is energy conservation and, fundamental to that, you can't shiver." In other words, we have to find a way to make the human body want to hibernate.
One of the main problems is that we still don't know all that much about what's going on internally while an animal is hibernating. Importantly, we're quickly making progress in that area. A 2011 finding showed that the brain's A1 adenosine receptor (which has many roles but is important in promoting sleep) is at least one potential trigger in inducing hibernation in animals that do regularly hibernate. Scientists are now able to act on that receptor to cause an animal to go into a hibernative state, which Drew calls a "really huge breakthrough."
"We have a whole lot more fine tuning to figure out," she said. "You can't say the A1 receptor is the thing causing hibernation because we still don't know the whole picture, but it's one component that is a sufficient switch to put them into that state."
This finding is potentially more important than the studies done in the 1960s (and also more recently), in which hydrogen sulfide was given to mice to shut off metabolism and induce what Drew said is a "hibernation-like state." As those studies progressed into larger mammals and mammals that don't normally hibernate, well, it just didn't work.
But humans (and all mammals) have an A1 receptor, and that's where much of the work is currently focused. Drew and others hope to soon attempt to induce hibernation in pigs—an animal that doesn't naturally hibernate, is large, and doesn't have much "brown fat," which generates body heat and is found in hibernating animals. If she or someone else can cause a pig to hibernate, well, that'd be an astounding result with potentially very important ramifications for the future of humans.
"I'm excited to try it," she added.
If humans could reliably hibernate, experts in the field say that, in addition to treating cardiac arrest and stroke victims, the process could be used as a treatment for neurological disorders such as Alzheimer's and Parkinson's ("Cortical neurons de-connect from each other" while in torpor, Cerri said. "The fantastic thing is when you wake up, the synapses regrow very fast and intensely"), gastrointestinal disorders (gut microbiomes change and are more easily influenceable when in torpor), and perhaps even memory manipulation ("if you interfere with the lost synapses, maybe your memory gets erased," Cerri said).
And then there's space.
While there are many potential terrestrial applications for human hibernation, much of the research is still being pushed forward by space agencies. Science fiction, after all, is often speculative. In February 2014, a report commissioned by NASA and conducted by the Atlanta-based SpaceWorks Enterprises consultants found "no show stoppers" that would prevent humans from hibernating on a long space mission. The presentation understandably raised a few excited eyebrows in the space community, not just because of what human hibernation would mean for human health, but what it would mean for the physics of space flight.
According to the paper, a mass reduction of up to 44 percent could be achieved on a mission to Mars if most of the people onboard were sleeping for most of the trip. Most of the reduction came from pulling out human life support needs, such as food and water, and reducing oxygen requirements. In addition, research on animals suggests cells that are in a state of torpor aren't affected as strongly by radiation, which is one of the major concerns of deep space travel.
"It would be a biotechnological approach to suspended animation, which is a very seductive idea"
Because mass is the most important (and most expensive) part of any deep space mission, human torpor is being looked at as perhaps the most important potential breakthrough for any long-term crewed missions.
"The more you work on the engineering problem, the more you realize that we're going to need a breakthrough technology to have any significant impact on the weight of the mission. To take the mass down even 5-10 percent, you need 20-30 minor miracles where everything works together," John Bradford, a researcher at SpaceWorks Enterprises, told me. "With torpor, you get a roughly 50 percent mass savings. If you were to dedicate your time into any one particular part of a Mars and human exploration project, this technology would demonstrably have the most significant impact to the mission."
After that initial fact-finding mission, SpaceWorks Enterprises hasn't gotten any more outside funding to work on the problem. It's simply too early to apply basic research to humans, according to Kelly Drew, who says it's work on non-hibernating animals that will eventually provide the breakthroughs necessary for human trials.
"We need to not take too big of a step and fail and get so disappointed that everyone gives up on the idea," Drew said. "Sometimes I think that's what happens with these tough problems. We need to systematically go through the process and figure it out."
Bradford says his team has been working internally on the project (since the initial NASA project, his company has done a mockup for a 100-person Martian colonization transporter that would have 96 people in stasis for a couple weeks at a time, with four caretakers watching over them for the whole mission), but it's still applying for grants that would allow his company to work more specifically on the technology to actually induce torpor.
If that funding won't come from NASA, maybe it'll come from Europe. More than a dozen scientists affiliated with the European Space Agency met earlier this month to discuss how we might make people hibernate.
"We've got sleep researchers, neonatologists—after birth we undergo very strong metabolic changes—metabolic experts, neuroscientists, zoologists, cell biologists. There's a large group of disciplines that can contribute to answering these questions," Jurgen Bereiter-Hahn, a neuroscientist at the Goethe University in Frankfurt and one of the ESA consultants, told me. "Nobody knows how it's done, nobody knows specifically how animals do it, but we're making proposals to follow a line of research that will discover how to bring humans into this state of torpor."
Cerri, who is also on this ESA team, says that, like Drew's team, he's in the initial stages of pig hibernation trials that he hopes could prove hibernation is possible in traditionally non-hibernating animals. Bereiter-Hahn said projects like Cerri's are the ones the ESA is most interested in funding, and are the most pragmatic way forward.
"Working on the A1 receptor is the state-of-the-art on what could be done. We're not sure how you'd do that [in humans], but we're working on designer drugs that would act on the receptor," Cerri told me. The drug would stay in the body until it wore out, which would mean a person would wake up according to a predetermined schedule or perhaps an "antidote" could be developed that would cause a person to wake up. "It would be a biotechnological approach to suspended animation, which is a very seductive idea."
If Cerri or Drew is successful, we may be looking at a future in which cryosleep is not only possible, it's routine for a whole host of terrestrial maladies and necessary for deep space missions.
"On one hand, we know quite a lot. We know the main areas of the brain, we know at least some of what hormones are involved," Bereiter-Hahn said. "How long it'll take to get to the result we'd like to have, I can't tell you. But I'm hoping that in a couple years we will at least be able to manipulate the metabolic status of people."
You'll Sleep When You're Dead is Motherboard's exploration of the future of sleep. Read more stories.