SpaceWorks, a NASA contractor, has proposed Mars transports and studies of induced torpor for their passengers.
Someday astronauts packed inside rocketing tin cans bound for Mars or worlds even more distant may be protected from radiation and space sickness by being placed in a state of torpor, an ultra-low metabolic rate induced by nitrogen gas, icy saline, or some as-yet-undiscovered animal proteins. While their cellular activity is kept at a fraction of its normal rate, theyll hibernate in spinning pods like bears as they hurdle through space for months at a time. They may lie in white hibernation pods like the cryo-preserved astronauts in futuristic fantasies like 2001: A Space Odyssey, Alien, and Avatar.
More likely, though, astronauts and space colonists will learn a few tricks from dehydrated snails, which survive for a year or more ingesting nothing; giant pandas subsisting on low-calorie bamboo; leeches that survive a liquid nitrogen bath; children who have been submerged in frozen ponds yet can still be resuscitated; or skiers buried in an avalanche and brought back to life ever so slowly, reborn from a super-cooled, dreamless state.
Scientists call this phenomenon torpor-induced hibernation. Once considered outlandish, torpor inductionthe old term was suspended animationis under serious study for long-duration spaceflight.
This is due in part to advances in low-temperature surgery, but also to an increased understanding of cases like one documented in 1995 in the journal Prehospital and Disaster Medicine. A four-year-old boy fell through the ice of a frozen lake in Hanover, Germany. A rescue team pulled him out but could not resuscitate him in the field. His pupils were fixed and dilated, and he remained in cardiac arrest a full 88 minutes. Upon admission to the hospital, his core body temperature was 67.6 degrees Fahrenheit, a sign of severe hypothermia.
Twenty minutes later, as doctors worked to warm the boys chest cavity, the ventricles of his heart started contracting. Ten minutes after that, his heart resumed normal sinus rhythm. The boy made a full recovery and was discharged two weeks later. His doctors believed the icy lake had rapidly cooled his body to a state of protective metabolic torpor, preserving all vital organs and tissues while reducing the need for blood oxygenin effect, saving the boys life. Cases like this are exactly why we think that very deep hypothermia can allow our patients to survive, writes Samuel Tisherman, director of the Center for Critical Care and Trauma Education at the University of Maryland Medical Center, in an email. The key is cooling the brain either before blood flow stops or as soon as possible after blood flow stops. The colder [it gets], the longer the brain can tolerate not having blood flow.
Therapeutic hypothermia has become a part of surgical practice. Experimental procedures with cooling started as early as the 1960s, mostly in cardiac and neonatal cases. Babies were placed in cooling blankets or packed in ice and even snow banks to slow circulation and reduce oxygen requirements before heart surgery.
Today, physicians use moderate hypothermia (roughly 89 degrees) as a staple of care for some newborns in medical distress, such as those born premature or suffering from fetal oxygen deprivation (hypoxia). The babies are treated with cooling caps for 72 hours, which lower their metabolism just enough to reduce tissue oxygen requirements and allow the brain and other vital organs to recover.
By the same token, surgeons apply cooling and metabolic suppression to patients whove suffered various physical traumas: heart attack, stroke, gunshot wounds, profuse bleeding, or head injuries resulting in brain swelling. In emergency situations, anesthetists can insert a slim tube into the nose that feeds cooling nitrogen gas directly to the base of the brain. In one experimental therapy, surgeons insert a cardiopulmonary bypass cannula through the chest and into the aorta, or through the groin and into the femoral artery. Through these tubes, they infuse cold saline to reduce core body temperature and replace lost blood. Once the trauma surgeon has control of bleeding, a heart-lung machine restarts blood flow and the patient is given a blood transfusion.
If you get cold fast enough before the heart stops, the vital organs, particularly the brain, can tolerate cold without blood flow for a time, Tisherman explains. He is performing a clinical trial of this cold saline replacement technique in critically injured trauma victims in Baltimore, and he expects the study will last at least until the fall of 2018 and possibly later. The ensuing hypothermia rapidly decreases or stops blood flow for an hour or so, cutting oxygen requirements and giving surgeons time to repair critical wounds and, ideally, warm the patient back to life.
Today, the aerospace community is looking to medically induced hypothermia and the resulting metabolic stasis in transport habitats as a way to save space and mass, along with freight, fuel, food, and frustration on the months-long flights to Mars or more distant planets. The studies are just beginning. One challenge is medical: Whats the best method for putting healthy astronauts into torpor? Even though therapeutic hypothermia is well understood in operating rooms, keeping people in deep space chilled and sedated for weeks, months, or years on end is an entirely unknown area of inquiry. Some scientists studying hibernation in animals suggest that other means of suppressing metabolism would be better: Specialized diet, low-frequency radiation, even the use of proteins that trigger hibernation in animals like bears and Arctic ground squirrels have been shown to regulate metabolic rates safely and, in most cases, reversibly.
Another obvious hurdle is funding. How much will NASA prioritize research into metabolic stasis, both animal and human, when exploratory budgets are being reduced? Pete Worden, former director at NASAs Ames Research Center in California and now the executive director of Breakthrough Starshot, says that with NASAs emphasis on synthetic biology and the ability of organisms to survive and function in exotic environments like Mars, its probably inevitable that the hibernation area is going to get funded.
That optimism is hardly universal. People are frustrated, says Yuri Griko, a Moscow-trained NASA radiobiologist and lead senior scientist in Ames space biosciences division. When Sputnik was put up in space in 1957, our generation was so excited, so inspired, and we believed that wed be on Mars in the millennium. But now its 2016 and were still not on Mars. Its personal for people like me because we expected to be much more progressed than we are right now.
Griko acknowledges that metabolic suppression research is in a kind of limbo itself. He began at NASA in 2005 after spending five years at the biotech outfit Clearant, Inc., using ionizing radiation to inactivate pathogens in therapeutic blood products, transplant organs, and commercial biopharmaceuticals. NASA then invited Griko to research ways to protect astronauts from deep-space radiation. It turns out that metabolic suppression is one of the most effective mechanism nature provides.
When animals go into hibernation their bodies survive radiation without significant damage to their cells. Girko believes this is because metabolic suppression mitigates radiation-induced damage by reduction of biochemical processes and excessive oxidative stress. Hypoxiareduced oxygen consumptionis one of possible explanation for the radioprotective effect: In hypoxia, production of oxygen free radicals and hydroxyl radicals is reduced. Since most ionizing radiation-induced cellular damage is caused by radiation induced free radicals, suppression of metabolism (and as a result of oxygen consumption) significantly inhibits ionizing irradiation-induced cells apoptosis and increases cellular viability. And this protective effect is even more dramatic at lower temperatures. XXX
Griko speculates that hibernation may also protect animals from the muscle atrophy and bone loss people typically experience in microgravity. Humans who eat a balanced diet while confined to bed rest for 90 days lose a little more than half of their muscle strength, Griko says. But bears who consume nothing and are confined to their dens for the same length of time or slightly longer lose only 25 percent of muscle strength and exhibit no signs of bone loss. He notes that animals capable of hibernationtortoises and pocket micehavent been flown in space in decades.
NASA declined his request for flight experiments involving hibernating animals. His current research is limited to surveys of existing hibernation studies worldwide, along with his own laboratory discoveries on stasis in mice, leeches, and snails. Griko proposed a 2015 international conference on torpor that would have brought together the worlds hibernation experts to discuss deep-space applications. NASA declined to fund it, though Griko still hopes to raise the money.
There are significant barriers to torpor research if were serious about going farther in space, says Leroy Chiao, a former NASA astronaut and International Space Station commander who spent 193 days in orbit between October 2004 and April 2005. Animal research is a particularly sticky problem. Even research on simple primates starts getting people up in arms, he says.
Jason Derleth, a program executive with NASA Innovative and Advanced Concepts in Washington, D.C., sees reason to hope. Under his watch, NIAC has awarded two innovation grants in the last three years supporting one companys detailed plans for torpor-enabled Mars transfer habitats. The project leader, SpaceWorks Enterprises, Inc., of Dunwoody, Georgia, about 20 miles north of Atlanta, is an aerospace design contractor for NASA and the Department of Defense and has done work in the development of tiny CubeSat satellite constellations. But its torpor thats captured the imagination of SpaceWorks president and chief operating officer John Bradford.
Ive asked myself for 15 years how to engineer materials, structures, and propulsion systems to enable a mission to Mars and its moons, he says. Bradford is a Ph.D. aerospace engineer who has led several NASA, Defense Advanced Research Projects Agency, and Air Force Research Laboratory projects designing military spaceplanes. He was also a consultant on the 2016 science fiction film Passengers, wherein Jennifer Lawrence and Chris Pratt played interplanetary settlers who wake from hibernation early. Were not in the vein of an Apollo mission anymoreno more flags and footprints, he says. We need to become a two-planet species.
Bradfords engineering and medical team used the first of those NIAC grants, issued in 2013, to design a compact zero-gravity, rigid-structure habitat based on the International Space Station crew module designs. The habitat featured closed-loop oxygen and water production systems, direct access to the Mars ascent and descent vehicles, and support for a crew of six, all of whom would be kept in torpor for the entire six- to nine-month Mars journey.
The proposed medical treatment relies on using techniques similar to the ones surgeons perfected to induce hypothermia. For example, cooling nitrogen gas could be fed to astronauts via nasal cannula, or tubes, lowering brain and body temperatures to between 89 and 96 degreesclose enough to normal to maintain torpor without overcooling the heart or increasing the risk of other complications. Cooling tends to decrease the bodys ability to clot, Tisherman says. He has noted that patients who are cooled to mild levels of hypothermia93 degreesfor 48 hours or more have more infections.
In the SpaceWorks habitat, robotic arms in the module would be programmed to carry out routine chores, manipulate astronaut limbs, and check body sensors, urine evacuation lines, and chemical feeds. Robots would administer electrical stimuli to astronauts muscles to maintain tone, along with sedation to prevent a natural shivering response. The astronauts would also receive complete nutritionelectrolytes, dextrose, lipids, vitamins, etc.via liquid (known as total parenteral nutrition) through a catheter inserted in the chest or the thigh. SpaceWorks outfitted TPN supplies in the experimental module to last 180 days; should the habitat be required for a prolonged Martian stay, the module would have another 500 days worth of nutrition.
In all, the SpaceWorks Mars Transfer Habitat reduced total habitat mass, including consumables, to 19.9 tons (low-Earth-orbit weight). By comparison, NASAs TransHab habitat, with consumables specified in the agencys Mars Design Reference Architecture 5.0, weighs 41.9 tons. Thats a 52 percent decrease in mass. Compared with the NASA DRA model, SpaceWorks was able to shrink total habitat consumables by 70 percent.
NIAC officials, naturally, were intrigued. SpaceWorks made an interesting proposal, Derleth says. People have been studying torpor for medical applications. But no one as far as we could find is actually doing an engineering study of what cryo-sleep or torpor would actually do to the architecture of a mission.
In 2013 NIAC awarded SpaceWorks a Phase 1 grant of $100,000 to develop a rough torpor-enabled architecture for exploration-class missionsthose with four to eight crew members heading to Mars or its moons. But the agency balked at the idea of putting all crew members in torpor for the entire journey. What about medical or spacecraft complications? How long could astronauts stay under without psychological or physical damage? What if some complication required their premature awakening? What about the slow waking and warming times to get the astronauts out of hibernation?
These questions sent the SpaceWorks team back to the drawing board. They designed a crew habitat for torpor that would keep at least a few astronauts awake on a rotating basis for piloting and interventions (as in the 1968 movie 2001, in which two crew members of the Jupiter-bound spacecraft Discovery remain awake while the others sleep).
Then Bradfords team moved further. Designing three interconnected habitat modules for a 100-passenger settlement class Mars missioncolonists, in other wordsthe team produced a spacecraft and habitat that departed completely from anything in NASAs plans. The SpaceWorks settlement-class craft includes two compact, rotating habitat modules, each accommodating 48 passengers in torpor. Rotation at varying speeds would produce artificial gravity to mitigate astronauts bone loss.
But in the bolder sentry mode proposal, a separate habitat module would accommodate four care-taking astronauts on duty throughout the mission, although one or more could be rotated with others in torpor to keep crews fresh.
You get 80 percent of the benefits by cycling through the hibernating crew and waking some up, rather than turning out the lights on everybody for six months, Bradford says. Spacecraft accommodating settlers in torpor would be lighter, which would enable much greater velocities, shorter voyages, and, possibly, more efficient radiation shielding because of the radio-protective effect of metabolic stasis. Further, Bradford says, hibernating astronauts wouldnt experience motion sickness, a common problem on the International Space Station.
But what would torpor in space feel like? Not like being frozen dead in cryogenics, then being revived after decades or hundreds of years, according to Doug Talk, an obstetrician who has used therapeutic hypothermia to treat oxygen-deprived babies. [Cryogenics] has had zero success with that, Talk says. The human body isnt meant to be frozen; its mostly water, and when water expands [as it does when it freezes], it produces cellular damage.
More likely, astronaut torpor will be like coma, a state hovering between dreamless sleep and semi-conscious awareness. Coma patients display cycles of brain activity that alternate between seeming wakefulness and non-REM sleep, Talk explains. Even though coma patients are unable to move, their brains remain active and even responsive to outside stimuli, including verbal commands.
Bears experience hibernation in similar ways; their core temperature drops only a few degrees (similar to the mild-hypothermia temperature range in humans), while their metabolism drops 75 percent. Bears in northern climates can remain in torpor for seven to eight months without eating or drinking, and pregnant female bears will bear their young and nurse them even in hibernation.
Someone in torpor will act like the bear does, Talk theorizes. Theyll cycle through non-REM sleep and being awake. And like bears when they finally wake up, theyll be sleep deprived.
In May 2016, NIAC approved a second phase of the SpaceWorks project, this time releasing $250,000 to extend first-phase engineering, operational, and medical research plans. Phase 1 projects have proven that what theyre talking about is real, Derleth says. Were very happy to see Dr. Bradfords progress.
In addition to habitat engineering refinements, the SpaceWorks team initially proposed a two- to three-week hibernation test with a small number of healthy pigs. Pigs, like humans, are natural non-hibernators, and are closer in size and physiological responses to torpor induction than many other primates than mice or snails, obviously. Derleth says agency regulations prevented NASA from funding the pig study.
So SpaceWorks submitted an alternate proposal: research existing metabolic suppression experiments comprehensively to come up with a near-term road map for technology development, including more-methodical animal research leading to human trials. This summer, NIAC will conduct a mid-term review of SpaceWorks progress and determine whether to award them an additional $250,000.
We continue to believe that live-subject research will be necessary to advance this torpor technology toward longer durations, Olds wrote in a follow-up email. That step may require private sponsors.
Regardless of who pays for it, testing with animals continues to raise ethical questions. I think NASA is right: Slow is the way to go, says Arthur Caplan, director of the division of medical ethics at New York University Langone Medical Center. While theres enthusiasm for suspended animation for long durations in space, NASA doesnt need any more troubles from animal rights activists. Pigs are somewhat physiologically similar to humans, so pigs are a reasonable animal model for testing. Though its fair to say to critics: The number of pigs involved in this kind of study wouldnt amount to ones weeks breakfast for the average American.
Sci-fi movies and novels have romanticized torpor, Caplan says, suggesting humans could move in and out of that coma-like state without difficulty. That might not be the case. Eventually, torpor will be tested in humans, and those humans will be unusual peoplemost likely test pilots, Caplan predicts. These people take risks every day; they understand the physiological risks because they test jets and know many colleagues who have died. Ive had astronauts tell me theyll enroll in any experiment just to get into space. Our job is to rein them in.
Human trials, if they happen, would be an unprecedented step. No one has ever tried to use hypothermia to suppress the metabolism of a person who wasnt severely sick or injured, much less super-healthy astronauts. In fact, weve had lots of healthy people who have volunteered for long-term torpor experiments, Talk says. Theres a pent-up demand for people who want to punch out of life for six months. Im sure the FDA wouldnt approve of that.
Meanwhile, Talk has invited two experts on therapeutic hypothermiaAlejandro Rabinstein, the medical director of the neuroscience intensive care unit at the Mayo Clinic, and Kelly Drew, a University of Alaska neuroscientist investigating animal hibernationto join SpaceWorks research team. Drew and other scientists at the University of Alaskas Institute of Arctic Biology are studying the hibernation patterns of endothermic animals like hedgehogs, Arctic ground squirrels, and bears. The hope is to find the key to a healthy hibernation state (and the signaling cascade in the brain that induces it) that could be adapted to human astronauts without side effects. The Arctic ground squirrel, for example, cools itself to 32 degrees in winter. No scientist understands exactly what triggers its hibernation, although a particular brain and muscle receptorthe A1 adenosine receptorappears to make the squirrel grow cold and sleepy, only to emerge with minimal bone and muscle loss eight months later.
Adenosine is a neuromodulator that plays a role in sleep and brain excitability, Drew says. Its ubiquitous in animal brains. She has been able to induce hibernation in hamsters and mice by using a drug to stimulate their A1 adenosine receptors. Drew can actually reverse hibernation by using another drug to block the same receptor, which wakes the animals up. But the signaling cascade and genetic makeup of humans are far more complex and may take years or decades to decipher. And not all hibernators hibernate in the same way: The only primate known to do it, Madagascars fat-tail dwarf lemur, spends seven months a year in torpor, mostly in hot weather; it survives by consuming the fat stored in its tail. Scientists have found that low metabolic rates in animals are not dependent on low body temperatures, suggesting that astronauts can be put into torpor without the complications that could arise with prolonged low-temperature hibernation.
Meanwhile, Rabinstein, who plans to help SpaceWorks evaluate mild hypothermia to induce torpor, says the techniques that work in an ICU might not be so reliable in space.
The fact that little children have drowned and survived in ice ponds and lakes is remarkable and has given us hope, he says. But can we transform this [understanding of deep hypothermia] into a more mild degree of hypothermia and allow people to tolerate it for a longer period of time and get away with it, without psychological or physiological stress? We have to see, but we think there is a a chance.
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Sleeping Their Way to Mars - Air & Space Magazine
