The Hibernator’s Guide to the Galaxy - WIRED

The Hibernator’s Guide to the Galaxy - WIRED

The Hibernator’s Guide to the Galaxy - WIRED
Nov 24, 2022 6 mins, 30 secs

An Arctic ground squirrel—the most extreme hibernator on the planet—can spend up to eight months a year in a torpid state. .

The creature, an Arctic ground squirrel, was just hibernating, as it does for up to eight months of the year.

During that span, the animal's internal temperature falls to below 27 degrees Fahrenheit, literally as cold as ice.

In 2001, astronauts lie down in sarcophagus-like hibernation pods, where their hearts beat just three times a minute and their body temperature hovers at 37 degrees Fahrenheit.

Early on in his research, Bradford glimpsed some promise in therapeutic hypothermia, a medical technique in which people who have experienced cardiac arrest are chilled—typically with intravenous cooling fluids—until their internal temperature reaches as low as 89 degrees Fahrenheit.

Brenda Stolyar.

Brenda Stolyar.

And so Bradford began to seek counsel from the small community of hibernation researchers, scientists devoted to studying the bears, bats, and lemurs for whom regular torpor is a fundamental aspect of existence.

By then, the University of Alaska's Kelly Drew had been researching the Arctic ground squirrel, the most extreme hibernator on the planet, for more than 20 years.

Kelly Drew has been studying the brains of hibernating Arctic ground squirrels since 1992.

Brenda Stolyar.

It was during the salmon study that Brian Barnes first plunked an Arctic ground squirrel into Drew's hands.

Instantly curious about what was taking place inside the critter's brain, a topic that had scarcely been researched, Drew began to examine hibernating ground squirrels using microdialysis, a technique in which tiny tubes are inserted beneath a living creature's skull to harvest samples of neural chemicals.

So Drew was stunned when she couldn't detect any such damage after performing microdialysis on the torpid squirrels.

“And so we started talking about hibernation as being a very protected state—it really seemed to protect the brain from injury.” This revelation made Drew think there could be tremendous value to replicating that state in humans.

For a brief moment early in the Cold War, hibernation research flourished in the United States.

(In one ethically shaky experiment, the lab's personnel paid several Indigenous inhabitants of Chilean Patagonia to wear temperature sensors and ventilated plastic hoods while they slept in freezing canvas tents.) Hock developed a keen interest in bears during his stint in Fairbanks, and he lamented how little was known about the changes in the animals' metabolism during hibernation.

Brenda Stolyar.

In 1960, Hock published a paper entitled “Potential Application of Hibernation to Space Travel” that offered the first sober, detailed look at how the budding American space program might benefit from the research he was helping to pioneer.

Hock mustered the courage to creep into sleeping bears' dens and stick thermometers in their rectums, a gambit that allowed him to assess just how much their internal temperature declined during their annual torpor.

If humans, like bears, were able to maintain an internal temperature about 13 degrees colder than normal, he estimated that “aging should occur at half the normal rate during this period.”.

“It's a gamble for a young professional scientist,” says Barnes, who introduced Drew to ground squirrels in 1992 and was the Institute of Arctic Biology's director from 2001 until 2021.

But Drew, whose kindly demeanor belies her tenaciousness, was so captivated by the Arctic ground squirrel that she plunged into hibernation studies with zeal.

To make that happen, she needed to identify the chemicals that trigger hibernation in Arctic ground squirrels, then test whether those might have a similar effect in humans.

Drew, who became an assistant professor at the Institute of Arctic Biology in 1993, initially hypothesized that gamma-aminobutyric acid, a neurotransmitter commonly known as GABA, was chiefly responsible for sparking hibernation in her squirrels.

But when Drew dosed her squirrels with GABA and an array of related chemicals, none brought about any sort of stable, long-term torpor?

Years slipped by in this frustrating manner: Drew celebrated her 40th birthday, mentored dozens of graduate and undergraduate students, and watched her daughter become a teenager while her efforts to find the molecular key to hibernation remained mostly stuck in neutral.

In 2005, a dozen or so years into Drew's research on the squirrels, an undergraduate chemistry major named Benjamin Warlick joined her lab as an assistant.

Brenda Stolyar.

Brenda Stolyar.

Sure enough, when she dosed her ground squirrels with CHA, a drug well known for stimulating the A1 adenosine receptor, the animals promptly cooled down and began to hibernate.

Still, Drew was encouraged enough to begin working on a paper for The Journal of Neuroscience about the drug's mechanism of action in the Arctic ground squirrel.

Brenda Stolyar.

Brenda Stolyar.

By 2014, Drew had achieved such excellent results in her experiments on rats that she applied to patent her invention: “Methods and compositions for the treatment of ischemic injury to tissue using therapeutic hypothermia.” The first illustration in the application is a photograph of an Arctic ground squirrel curled into its trademark hibernation pose, a nod to the small moment in 1992 that had altered the course of her life.

The firm had just secured a second tranche of NASA funding to press forward with its human-torpor research, and John Bradford invited Drew to become his company's chief hibernation consultant.

The drugs steadily and safely lowered the animals' internal temperature to between 86 and 90 degrees Fahrenheit—not quite as chilly as the state doctors can achieve using intravenous fluids on humans, but close.

“And they don't need intubation, and they don't need feeding tubes.” She and her daughter began working on their own paper, proposing several promising avenues of inquiry based on Martin's genomic analysis of the thirteen-lined ground squirrel, a close relative of the Arctic ground squirrel.

One was to investigate further a receptor called TRPM8, which plays a crucial role in helping thirteen-lined ground squirrels thermoregulate during hibernation.

Brenda Stolyar.

Brenda Stolyar.

In March 2018, NASA invited Drew, Martin, and a handful of other luminaries from the hibernation community to a two-day conference in Mountain View, California—an event billed as the agency's first-ever “space torpor workshop.” The meeting was an opportunity for the biologists to make the argument that, if provided with sufficient backing, they could help humans achieve at least some level of true hibernation in the next 10 to 15 years—a timeline that dovetailed nicely with NASA's plans to send humans to Mars in the late 2030s or early 2040s.

But the report also asserts that, based on the current pace of research, NASA could begin testing hibernation technologies such as Drew's drug cocktail on human subjects as early as 2026.

In a 1972 experiment, for example, scientists found that ground squirrels that were irradiated while hibernating had a much higher survival rate than their fully conscious peers.

Brenda Stolyar.

Brenda Stolyar.

“One lesson I've gotten from the physiologists studying hibernation is that we would be very naive to think that we're going to find one single drug that just lets an animal or a person go into hibernation,” Callaway says

Drew is studying, and then another drug some other sleep researcher is studying

Callaway doubts that when those astronauts sleep they'll ever get as cold as the Arctic ground squirrel or have metabolisms as low

But he notes that bears are pretty effective hibernators too, and they reduce their internal temperature by only a few degrees while snoozing through a winter

Brenda Stolyar

Brenda Stolyar

But thanks to university-based researchers like Drew who've solved some of the fundamental mysteries of hibernation, the private sector is taking notice of its potential

Brenda Stolyar

Brenda Stolyar

Arctic ground squirrels snap back to their old selves within hours of warming up

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