Learning to sleep like a bear could save your life

Ole Frøbert, a cardiologist, cozied up to his next patient, gently turning blood-filled tubes and placing the samples into a plastic bag.

But drawing the blood had been more difficult than Frøbert was used to, given the fat, fur and freezing temperatures.

“It’s not easy to puncture a bear vein,” he said.

Normally a doctor who works at Örebro University Hospital in Sweden and Aarhus University in Denmark, Frøbert had snowmobiled and snowshoed into Swedish bear country, eager to answer the question: How exactly do bears survive their long winter snooze without dying?

Blood clots, bed sores, bone loss, muscle deterioration — there is a whole host of ailments bears and other hibernating animals appear to avoid during their torpor.

So doctors and veterinarians around the world are probing the deep-sleep ability of hibernators and using those insights to develop drugs to treat cardiovascular issues and other ailments in people. Frøbert’s work to understand the mystery of bear blood is just the latest in a bevy of research into bears and other hibernating animals. Even space agencies and militaries are putting money into hibernation research in the hopes of harnessing discoveries to help astronauts endure the rigors of space travel and to treat injured soldiers.

“You can learn really a lot from nature,” said Manuela Thienel, a cardiologist at Ludwig Maximilian University of Munich who worked with Frøbert and led a recent study on hibernating bears. “Far more than we think.”

With so many drug trials and other medical studies focused on testing treatments on lab rats and mice, the work is part of a movement looking toward animals not traditionally studied to gather insights about the strange ways their bodies work, with the hope of developing new medicines for humans.

“I was a little fed up with the way we traditionally do medical research,” Frøbert said, starting with a disease and experimenting on mice and rats to find a treatment. “With the bear, it’s the other way around,” he said.

The hibernating brown bear is “an animal that doesn’t get disease, but it should,” he said. “This is a living library of biological solutions.”

‘We were onto something’

Brown bears are serious about their sleep. After the furry giants pack on the pounds in the fall, they can hibernate for up to eight months.

Yet no matter how tired, if a person were to try to sleep for that long, it would get ugly: Muscles would atrophy. Bones would weaken. Skin would scab with bed sores.

Hibernation, in fact, isn’t really a form of “sleep” as people experience it. It is something much more extreme: a deep state of energy conservation, with a brown bear’s heart rate dropping lower than 10 beats per minute.

As a cardiologist, Frøbert’s interest was blood. For humans, just taking a transatlantic flight boosts the risk of blood clots. But when bears emerge from their dens after their months-long snooze, they are spry and clot-free.

To figure out why, he and Thienel teamed up with bear researchers in Sweden. The team chased 13 bruins by helicopter during the summer and stalked their dens during the winter to collect their blood. Once, a darted bear briefly woke while a capture specialist was moving the bruin from a creek.

Because blood cells deteriorate quickly outside the body, they had to drive centrifuges and other lab equipment from Germany to a rural house in Sweden to conduct the analysis. “If you work with blood and platelets, you have to be really fast,” said Tobias Petzold, another cardiologist on the project.

The work paid off with the discovery that certain proteins — in particular, one called HSP47 — appeared with far less abundance in bear blood in the winter than in the summer, according to a paper published earlier this year in the journal Science.

This protein, which appears on the surface of platelets, helps blood cells stick together. When blood clots form after a cut, they stop the body from bleeding and help it heal. But when blood coagulates inside veins and doesn’t dissolve naturally, clots can be deadly.

To see whether the protein had the same effect in humans, the team turned to people with spinal cord injuries. Those patients, like hibernating bears, don’t get many blood clots, suggesting their bodies have found a way to decrease the presence of the protein after the injury.

The team found those patients have far less HSP47 than uninjured people. So did penned-up pigs and participants in bed rest studies.

“We were onto something,” Frøbert said.

[Is it true we need more sleep in the winter?]

Deep sleep

Other animals take hibernation to even greater extremes than bears.

Every autumn, the 13-lined ground squirrel burrows into the dirt, curls into a tiny fuzzball and falls asleep. But unlike in brown bears, the body temperature of these rodents, which live across the Great Plains, plummets to just above freezing during hibernation. It shakes its slumber every week or two and then chills again.

That led Ashley Zehnder, a veterinarian-scientist, to wonder: What is the squirrel doing to repair its body over and over again after nearly freezing to death?

She and her colleagues at Fauna Bio, a company she co-founded, looked at heart tissue sampled at different times in their hibernation. The team found genes activated in squirrels’ cells to protect and repair the heart when warming back up.

Fauna Bio is testing a compound meant to mimic that response in humans as a potential drug to help improve heart function after being damaged, with the aim of starting clinical trials soon.

“There definitely are more and more people taking a critical look at how we could use data from all kinds of different species to improve human health,” Zehnder said.

Easy to buy from breeding factories and to keep in captivity, rats and mice became an industry standard for medical research, with study after study building on the same animals.

But the plummeting cost of sequencing genomes, coupled with the greater sharing of data, has led to a boom in looking beyond so-called model organisms such as the lab rat and other animals often studied in science. Earlier this year, for instance, more than 100 scientists built and analyzed the genomes of 240 mammals in an effort to understand human disease.

Yet pressure to stick with old-school lab rodents is high. “I can’t tell you how many times those of us that study hibernation have had reviews come back saying, ‘Well, can’t you just do this in a mouse model?’,” said Hannah Carey, a professor emeritus at the University of Wisconsin at Madison who also studies hibernating ground squirrels.

One big problem is that lab rodents are often inbred, she added. “How close are they going to be to a wild situation?”

In another paper published in Science last year, Carey and her colleagues discovered the gut microbes of squirrels recycle waste chemicals and turn them into amino acids that the animals use to maintain muscle.

The discovery comes with the potential of probiotic supplements to help not only the elderly and malnourished with muscle wasting, but also allow astronauts to remain strong in zero gravity.

NASA and other space agencies have funded hibernation research in the hopes of putting space travelers into a hibernation-like state for long missions and enduring cosmic radiation. Though no one is sure why, hibernators are resistant to radiation.

“It’s an exciting time for hibernation biology,” Carey said. “People from outside of traditional hibernation world are wanting to come in and collaborate.”

‘Crazy projects’

At first, it was hard for Frøbert to get funding for the brown bear work given the “built-in conservatism in the medical research community.” But ultimately, his team worked with both NASA and the German Aerospace Center.

Now his team is searching for a chemical to develop a new blood-thinning medicine with fewer adverse side effects than existing drugs. A new drug may be five to 10 years away, the team said.

“We need to have some space for these crazy projects,” Frøbert said.