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http://www.wsj.com/articles/SB10001424052702303330204579246003604081632 

To Learn About Obesity, Researchers Turn to Grizzly Bears
In Washington State, researchers are studying grizzly bears, not the typical lab rat 

By JONATHAN D. ROCKOFF
Dec. 15, 2013 10:31 p.m. ET
PULLMAN, Wash.—On a recent visit to a laboratory where he researches obesity, Kevin Corbit walked over to one of the patients he is studying to say hello. Then he clasped a claw.

Dr. Corbit, a scientist at drug maker Amgen Inc., is conducting his research on grizzly bears. He believes insights gleaned from the animals, who can take in as much as 58,000 calories in a day and weigh 1,000 pounds, could reshape understanding of obesity and identify new treatments for a condition that has stymied doctors and drug developers.

"When I thought about obesity, I thought about Yogi bear," Dr. Corbit says. 

Ursus arctos horribilis isn't the typical lab rat. A grizzly can lift a heavy tree trunk—with one paw. In the wild, the bears win duels with wolves and mountain lions. They are powerful enough to tear through the side of a barn or even crush a small car. Also, the bears growl.

But bears do know a thing or two about weight gain, and that makes them more like people than rats whose genes are manipulated to make them obese.

In the weeks before hibernating, bears pack away enough apples, berries and salmon to put on 100 pounds or more under their brown fur. Their bad cholesterol jumps and blood pressure spikes.

But unlike humans, their health doesn't suffer. Bears' arteries don't clog from the gorging, nor do the animals battle heart attacks or turn into diabetics.
To figure out why, the researchers draw the bears' blood, biopsy their fat deposits and listen to their hearts—carefully.

Few places are available for this kind of bear study. Dr. Corbit travels from Amgen's Thousand Oaks, Calif., labs to Washington State University, which says it has the only facility in the world housing adult grizzlies for research. Behind chain-link fences, the 12 bears wander along grassy hills and among Douglas firs and Ponderosa pines, or they relax inside concrete dens and runs. When winter nears, they hibernate. 

Bears at the center, set up 27 years ago, are either born at the facility or rescued from places such as Yellowstone National Park because they got too close to humans and would otherwise have been euthanized. A few times, staffers have taken cubs home for several weeks, until they want to climb the curtains, roam around the house and gnaw on electrical cords. "They go from helpless to hellions," says Charles Robbins, the bear center's director. 
 
The researchers employ some unique safety precautions. Fences are electrified, and buried deep under the ground so the bears can't dig them up. The bears are kept in steel crates when examined, and anesthetized before scientists take some tissue. Because the animals are good at using their front paws for grabbing and holding, they're trained to present their back legs for blood draws.



Honey helps. As Dr. Corbit looks on one recent morning, a 10-year-old female bear named Mica stretches out inside a steel handling crate lapping up a honey and water solution from a bottle inserted between two crate bars. 

The honey diverts the attention of the 400-pound bear from Lynne Nelson, who, reaching through the crate, runs a probe across the grizzly's chest to get an ursine echocardiogram of the beating heart.



Dr. Nelson, an associate professor of cardiology at WSU who is collaborating with Dr. Corbit, works quickly. "Even a bear can get full of honey," she says.



Medical research is studded with the study of strange creatures, from sea squirts to zebrafish. Narcoleptic dogs have furnished insights into sleep disorders, while Antarctic penguins are providing lessons on the biology of fasting.



Yet most drug discovery takes place in rats and mice, as well as test tubes. Research on large, wild animals is unusual, partly because of the challenges.



A bloodied arm taught Carl Luer, who studies the cancer-resisting qualities of sharks at the Mote Marine Laboratory in Sarasota, Fla., to avoid lemon sharks. He prefers nurse sharks, which are "very amenable to handling," he says, and fine with the small volume of water held by the tanks he puts them in during exams. 

When Dr. Luer began the research around 1990, there was little information about the shark immune system. To figure it out, he draws the fish's blood (it requires help holding the sharks down and plenty of practice finding the blood vessels under a column of vertebrae in their tails) and performs surgery (first he puts the sharks in a cooler filled with water containing an anesthetic).



The challenges were worth it, Dr. Luer says, because of the opportunity to discover the mechanisms that evolved over 400 million years to protect the fish from illness. "I spent about 10 years trying to induce cancer in sharks but was not successful," he says. This year, he helped publish a paper identifying how certain compounds in sharks kill tumor cells.



Rare is a company such as Ablynx NV, a Belgian biotech, which scatters 150 llamas and alpacas across four farms for its work developing new drugs based on tiny disease-fighting antibodies unique to the animals.



The antibodies are also made by camels, but Belgium doesn't have a supply of camels. "They are also bigger and more difficult to handle than llamas and alpacas," says Ablynx CEO Edwin Moses. 
By working with grizzlies, Amgen is stepping outside the industry's research comfort zone, concedes Alexander Kamb, the company's research executive who greenlighted the project two years ago. But typical approaches to studying obesity have still left scientists scratching their heads, and the few approved drugs have been found to reduce relatively small percentages of body weight. 
 
Meanwhile, bears have figured out how to be healthily obese and then lose massive amounts of weight without problems.



"I want to learn how the grizzly bears work their magic," Dr. Kamb says.



Dr. Corbit, who says he had worked "exclusively on mice" before joining Amgen in 2011, says his studies of fat and blood samples suggest the bears respond to excessive weight gain differently than many people.



The bears seem to adjust their sensitivity to the hormone insulin that controls how much the fat and sugars in food are broken down and stored for energy. The bears are more sensitive to insulin while putting on pounds for hibernation. When hibernating a few weeks later, the bears shut off their insulin responsiveness entirely.



Over the next two years of the project, Dr. Corbit plans to explore how—eventually with help from sequencing the bears' genome. 

"That would really accelerate the discovery research for bears," he says.


Write to Jonathan D. Rockoff at [email protected] Reply