This last winter, the 11 grizzlies at the WSU Bear Center were doing what they do best: a lot of nothing, and Washington State University researchers want to know exactly how they do that so well.

 

Bears have a certain genius for hibernation⁠—they can pack on the pounds without getting diabetes or high blood pressure, sleep for five to six months straight without losing muscle mass or bone strength, and then, wake up and do it all over again. Understanding how they do this has a host of implications for humans from treating diabetes to preventing muscle atrophy in hospital patients and even allowing astronauts to withstand long periods in space.

“There’s an awful lot that bears can teach us in terms of their resilience to the development of disease,” says Heiko Jansen, WSU professor in integrative physiology and neuroscience. “We really have no indication that bears going through hibernation and being inactive suffer from all of the things that we do⁠—and they do all this year-in, year-out. It’s a reversible process which leads to the question: how is it that these animals can simply turn that switch on and off, and survive?”

Decoding that switch is proving enormously complex. Using RNA sequencing, WSU researchers and their colleagues published a study in 2019 that identified thousands of genes involved in bear hibernation. In the fat-storing-tissue called adipose alone, more than 900 genes expressed themselves differently during the warm months, when bears gorge themselves on food, than during hibernation.

WSU is well-positioned to take on these difficult questions as the home to the Bear Center, the only research facility in the world with a captive population of grizzly bears. Then, there is the research team with complementary expertise in physiology, genetics, ecology, and nutrition, whose published studies are drawing increased recognition to the research potential to help understand bear ecology and provide insight into conservation as well as human health.

“We’re getting more and more interest from other researchers that bears might be a good model for what they’re studying,” says Charles Robbins, the wildlife biologist who first launched the bear program at WSU 36 years ago.

Robbins’s work in nutrition with the captive grizzlies combined with investigations into wild grizzly bear and polar bear diets has led to a healthier, more fat-heavy diet for captive bears of all kinds. This work demonstrates one of the key values of the center, Robbins says.

“If you just study captive bears, or just study wild bears, there’s a severe limit to what you can do,” he says. “By putting them together, we can learn so much more.”

Then, there are the human health implications. Robbins and Jansen are currently collaborating with Texas A&M researchers on a muscle atrophy study in the bears that holds promise for helping humans recovering from bedrest as well as for astronauts who lose muscle from prolonged periods without gravity. The WSU scientists are also exploring ways to induce hibernation in other animals, a line of inquiry that might one day help humans take extended trips in space.

The bears seem eager to help. All 11 grizzlies at the center come when called by name. They stand on scales to be weighed, and even the biggest among them willingly offer their hind legs for blood draws. Earlier this summer, a grizzly named Frank demonstrated how that worked. When Bear Center manager Heather Keepers opened the gate to his enclosure and called him, he lumbered over to a special place in the metal-bar fencing and stood up, towering above Keepers as she stretched up an arm to offer him a bottle full of honey water.

After he had a good taste, she moved the bottle down, and the bear promptly sat all 600-plus pounds of himself down and stuck his hind legs through two paw-sized gaps in the metal bars. Undergraduate volunteers rubbed his legs while he slurped at the bottle. Each time Frank responded well to a request, Keepers marked it with a sound from a hand-held clicker as part of a training method based on positive reinforcement.

This was just a practice run, but despite the proverbial warnings over not poking bears, Keepers says the grizzlies don’t mind a needle jab as long as the honey is flowing.

“We work for money⁠—they work for honey,” says Keepers.

That love of sugar is a key scientific question, too. In a recent study, the researchers fed bears the simple sugar glucose at the wrong time of year. During hibernation, bears are not completely comatose and will get up occasionally, but they do not usually eat, drink, urinate, or defecate during that time.

Through the glucose study, the researchers learned that feeding during that period did interfere with the bears’ ability to hibernate. The study served as an extra warning to humans not to feed bears and provided an opportunity to see what’s happening when the glucose is introduced.

WSU evolutionary geneticist Joanna Kelley is currently using cell cultures taken for that study to investigate which genes are being activated in response to the ingestion of glucose before, during, and after hibernation. Her research team hopes to identify proteins that are changing the cells’ uptake of the sugar-regulating hormone, insulin. Diabetes in humans occurs when the body loses its ability to produce or respond to insulin.

“The ultimate goal is to translate all the things that we’re learning from insulin resistance in bears to humans,” says Kelley. “It’s a long road, but what we’re finding by looking at the bears is pretty fascinating.”

The Bear Center only draws blood from the bears a few times a year. Those samples are scientific gold for researchers not only at WSU but all over the world. The team grows cell cultures in petri dishes and freezes samples, so that they can be sent to researchers when they are investigating new questions. It’s almost like a library of cellular and genetic information, one that cannot be gathered easily from bears in the wild.

While 11 bears is not a huge number for animal models when compared to mouse studies, there are hopes to expand the center if funding can be found. Regardless, Jansen says, with careful work, the Bear Center researchers are able to design experiments with a lot of scientific rigor.

“We have a great community here that really loves the bears,” says Jansen. “It’s a vibrant group, and we collaborate with people all over the world to help them answer questions. That’s based on the recognition that what we have here is unique.”

 

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