February 17, 2020
Human Hibernation: The Future of Healing and Space Travel
Human Hibernation: The Future of Healing and Space TravelSource: The Burgundy Zine
What do arctic ground squirrels and black bears have in common? They’re both among the many animals that hibernate.
Except, hibernation isn’t just a long nap through the cold, dreary winter months. It’s a highly-regulated form of energy conservation that impacts how the brain and body function, says Kelly Drew, a University of Alaska professor and CEO of Be Cool Pharmaceutics.
So, what can we learn from hibernation and what might happen if we humans were to give it a try?
An Introduction to Hibernation
“Which Animals Hibernate?” by National GeographicSource: Which Animals Hibernate | National Geographic
“It’s not a strategy for getting cold, it’s a strategy for saving energy when food is scarce,” Drew explained during our interview on Saturday. “Animals hibernate even in mild climate if food is scarce.”
When an animal goes into hibernation, their rate of oxygen consumption sharply decreases and levels off before they begin to slowly cool, Drew said. There’s also a seasonal component to hibernation, where animals like the ground squirrel will only hibernate during winter.
“The ground squirrels that we studied, they hibernate no matter what,” she said. “You can not stop them from hibernating in the winter, and you can’t make them hibernate in the summer, regardless of what environmental conditions they’re under. They’re called obligate hibernators and there’s just some sort of rhythm in their physiology that tells them it’s wintertime.”
Torpor is another form of hibernation in which core temperature and metabolic rate are reduced, but it lasts for under 24 hours, whereas hibernation can last for up to nine months, says a 2018 Bioscience Horizons’ review.
There’s still a lot to be learned about the science behind hibernation and torpor. However, the energy conservation and protective properties of these natural phenomena have researchers interested in how hibernation could be applied to humans in a clinical setting.
Hibernation & Healing Humans
“Until now, [temperature] was pretty much just recognized as a vital sign,” Drew said. “If someone gets too hot or too cold, you have to give them something to get them in the range that you think they should be. But temperature actually has a way to influence bodily functions.”
Core temperature has a sweeping effect over a range of bodily functions: it regulates metabolism, inflammatory response, and evidence suggests that temperature is a driver for sleep, she added.
Although the link hasn’t been fully investigated, it’s also possible that temperature affects neurogenesis – the production of new neurons.
“Temperature regulates synaptic plasticity, so cooling the brain will cause synapses to retract and rewarming them causes them to regrow,” Drew explained.
The neuroprotective effects of low body temperature are particularly present in the arctic ground squirrels Drew studied.
“One of the most effective ways they protect their brain from injury is they get cold,” she explained. “The cold temperature, we found out, was really the most effective way they protect their brains from being injured by things like lack of blood flow.”
When the ground squirrels are cold, Drew said they don’t have action potentials so their neurons aren’t firing signals to one another.
Hibernation v.s. Coma
Although hibernation and a medically-induced coma may appear very similar, they’re entirely separate processes.
In a coma, core-brain functioning is suppressed with drugs but parts of the body, like the colon, continue to function, Drew explained.
“Hibernation is a coordinated downregulation primarily of this thermostat,” she continued. “Turning down the thermostat causes the animal to get cold, and the cold has a huge influence on turning down core brain function.”
Hibernation in a Clinical Setting
Taking a page out of the ground squirrel’s book, hibernation offers critical care teams the ability to protect their patients from brain damage, inflammation, and muscle loss.
“I am the leader of a new center here at the University of Alaska called Transformative Research in Metabolism,” Drew said. “It’s an NIH-funded program that the mission is just that: to understand basic mechanisms of metabolism and hibernation, and how to translate that and commercialize that for human health.”
Muscle maintenance is one of the areas Transformative Research in Metabolism is focusing on now, she explained.
“In hibernation, [animals] don’t move pretty much for eight to nine months,” Drew continued. “They don’t eat and they don’t move and they wake up fit and trim. They don’t lose muscle mass and they don’t lose muscle strength when they wake up in both the hibernating ground squirrels and black bears we’ve studied.”
One research group is looking at understanding the metabolic processes to help elderly patients preserve muscle mass. Elderly patients tend to lose more muscle than fat when dieting, which is detrimental to their health and fitness, Drew said.
While studying hibernation offers great insight for critical care treatment, inducing hibernation in humans is a meticulous process that requires a great deal of caution.
“The longer you keep a patient cold, the more complications they will have, particularly during the rewarming,” Drew explained. “That’s kind of where the technology is needing to be advanced to understand what’s going on there.”
However, BCP-019, the drug developed by Be Cool Pharmaceutics for inducing hibernation, gives clinicians a lot of control over the patient’s core body temperature.
“The idea is that the drug turns down the thermostat so the control of the body temperature is now in the hands of the clinician,” she said. “So they can cool or rewarm [the patient] at their will.”
The safe duration of induced hibernation in humans also varies depending on the age of the patient.
“For adults, the standard of care for cardiac arrest is 24 hours of cooling,” she said. “If you go longer than that, you do get greater risks. For babies, it’s called HIE – hypoxic-ischemic encephalopathy – and the standard of care is to cool them for three days. A baby that has compromised brain oxygenation or blood flow during birth will be immediately cooled and kept cold for three days.”
Furthermore, humans have to remain warmer than animal hibernators to keep their heart rate from becoming too irregular and potentially triggering cardiac arrest, she explained.
The human target cooling temperature is between 32 to 34 degrees Celsius, whereas the ground squirrels’ body temperature can dip as low as -2.9 degrees Celsius, according to a Scientific American article.
“If an animal or a human is at 32 degrees or 30 degrees, they need to rewarm very slowly,” Drew explained. “The standard of care is between 0.5 and 1 degrees per hour and the way it works with our drug is that they leave the drug on board while they rewarm them. [Clinicians] maintain control of the thermostat as they slowly rewarm, and you rewarm from external heat.”
Hibernating Beyond Our Horizon
ESA (European Space Agency) astronaut Luca Parmitano is pictured tethered to the International Space Station while finalizing thermal repairs on the Alpha Magnetic Spectrometer, a dark matter and antimatter detector, during a spacewalk that lasted six hours and 16 minutesSource: ESA astronaut Luca Parmitano is tethered to the space station| NASA Images
In addition to clinical applications, researchers have been investigating whether hibernation could help astronauts make it through long journeys through outer space.
“Cycling the crew in and out of the torpor state further reduces the burden on fully autonomous systems, ensures crew cognitive abilities are maintained, and enables use by NASA on early Mars missions,” says a 2018 SpaceWorks report. “Over time, it is reasonable to assume this capability can be further extended to periods of months to offer additional benefits.”
The hibernation habitats would consist of sleep-pods for the crew members to enter stasis after their departure from Earth or another area of space.
These pods would combine cooling technology with a minimal dosage of suppressive drugs and an A1-AR agonist.
Drew has actually worked with SpaceWorks president John Bradford and former NASA astronaut Leeroy Chiao, serving as a consultant for space-hibernation technology with critical care physicians and SpaceWorks engineers.
“They are very interested in using a drug to do exactly what we do, they’re very interested in our drug combination,” Drew said. “We got to talk about different approaches and it was just a lot of fun because the critical care physicians are very invasive, so they’re used to taking care of patients in critical care by sticking things in them and doing all kinds of things. I was coming at it more from what I see hibernating animals do, which is all very non-invasive – they just do it.”
However, Drew believes the technology will need to be further developed in a critical care setting before hibernation goes beyond our horizons.
The Work of Kelly Drew & Be Cool Pharmaceutics
An arctic ground squirrel emerging from the groundSource: Adobe Stock
After obtaining her P.h.D. in pharmacology, Drew continued her post-doctorate studies in neurochemistry at the Karolinska Institute in Sweeden, which she says has given her a biomedical perspective to the work she does today.
“I came back to Alaska and I thought I was gonna do the same stuff that I’d been doing [while studying], then a guy named Brian Barnes who has worked in hibernation for a long, long time handed me a hibernating arctic ground squirrel,” she said. “It was amazing, so amazing. I was always interested in how the brain and the chemicals of the brain regulated consciousness. And then I held this animal that was alive but was cold and it wasn’t moving.”
Drew said it was hard to see the ground squirrel breathing, but if you watched closely you could just see it breathe once every minute, sometimes once every three minutes. When she put her fingers on the ground squirrel’s chest, she couldn’t feel its heartbeat.
Utilizing her interest and background in neuroscience, Drew began investigating what brain systems were involved in the hibernation process.
Inducing Hibernation in Non-Hibernating Species
BCP-019 hasn’t been tested in humans yet, but Be Cool Pharmaceutics has studied it with other non-hibernating species like rats and pigs.
“The primary mechanism [of BCP-019], is turning down the [internal] thermostat,” Drew explained. “It’s affecting the output of the raphe pallidus, which is the premotor sympathetic nucleus that controls thermogenesis, so shivering and brown fat activation. We don’t think it works directly in the raphe, but indirectly that’s like the gate, so you see that the raphe is turning off.”
Although the drug only induced hibernation in arctic ground squirrels during winter months, Drew said the rats were able to undergo hibernation when given the drug at higher doses.
“One thing we haven’t done in summer ground squirrels is we haven’t tried to get them to respond to a higher dose,” she added. “We just haven’t had time, but we did do that in rats.”
Her team also saw similar results when putting the rats on a diet of every-other-day feeding, “But, that’s not really feasible for clinical application. You can’t put someone on every other day feeding because you don’t know when they’re gonna have a cardiac arrest,” Drew said.
BCP-019 turns off the cold-defense response, which was highly effective at getting pigs to stop shivering, she explained.
“In rats, when we give the drug either IV or ICD, it causes them to get very cold so we actually had to put a lot of effort into devising equipment that would keep them from getting too cold,” she continued. “And so that’s what we’re trying to develop, as we call it a first in class thermolytic.”
Kelly Drew’s Vision for BCP-019 and Be Cool Pharmaceutics
Right now, Drew says Be Cool Pharmaceutics will continue focusing on BCP-019 and studying it in humans.
“I will say that when it is successful, I hope that [Be Cool Pharmaceutics] can be a company that can continue to work n translating aspects of hibernation and mechanisms discovered in hibernation for clinical medicine,” she said.
In addition to the clinical applications and potential for space technology, Drew said she hopes this transformative drug can provide insight on a spiritual level.
“I don’t know if you’ve ever read this book, it’s called ‘Erasing Death,’ and there are many stories about people who have either drowned in cold water or are cold after a cardiac arrest [and they’re] really near-death or they die and come back,” Drew began. “I like to think of it as a spiritual experience. I hope this new realm of healing is really a meant-to-be thing and that there’s a spiritual connection there. Y’know, glory to God if it does in fact turn out.”
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