It’s the Dog in You
An Oklahoma veterinary scientist named Mike Davis says there's no doubt about it: The world's greatest athletes, of any species, are the canines who pull sleds at the Iditarod. Now, in a project funded by the Pentagon's research arm, he's coming up with ways to make us more like them.
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It's 6:15 A.M. as I approach the home of one of the world's greatest athletes. His name is Tony, and he lives in a tiny plywood shack about 30 miles outside of Fairbanks, Alaska. By all rights, he should be exhausted. He got up at four and ran 22 miles in a mid-September, pre-dawn chill, and he wasn't running on nicely paved roads. He ran across fields and through muddy ruts on dirt trails while he and a few teammates tugged against harnesses attached to an ATV. By any measure, it was an absurdly tough workout, and it was even more remarkable because this was Tony's first hard run in months. So I'm amazed to see him standing outside his door, looking refreshed and eager.
As you may have guessed, Tony is a sled dog, which means he's a mutt, with a little Siberian husky in the mix, who's been specially bred for speed, desire, and resilience. When Tony's in peak condition, his VO2 max a measure of his ability to take in and use oxygen in the bloodstream tops out at more than 200 milliliters of oxygen per kilogram of body weight per minute. (Back when Lance Armstrong was racking up multiple Tour de France wins, his famously high VO2 maxed at around 85.) Tony may be a little flabby now, but in a few months, when he's competing in the Iditarod, he'll be able to run an average of 100 miles a day over eight or nine days, working at 50 percent of his VO2 max for hours on end. As part of a team, he can run sub-four-minute miles for 60 or 70 miles.
“When it comes down to sheer capacity for prolonged exercise,” says Ken Hinchcliff, an Australian veterinary physiologist who's done more research on sled dogs than any other scientist, “there is no other animal, including humans, that comes close to competing.”
Some might argue the point by bringing up birds that can migrate for thousands of miles. But migratory birds aren't racing or pulling weight, and, more important, birds don't make good comparative models for human physiological studies. Tony and his mammalian kennel mates do, and they're helping scientists answer fundamental questions that could, in the near future, lead to new ways to enhance the performance of two-legged athletes like you and me.
THAT MAY SOUND far-fetched, since dogs and humans are so different, but Mike Davis, an Oklahoma State University veterinarian and exercise physiologist, thinks otherwise. Davis has brought me here, to the home of mushers Aliy Zirkle and Allen Moore, to show me the dogs up close and explain his complicated research. As he and I wade into a pack of 50 yelping, howling animals, he points out that dogs are large mammals, just like people. On the level of genes and regulatory proteins, we're surprisingly close cousins.
“When we figure out how dogs are regulating muscle proteins to accomplish what they do,” he tells me, “it is possible we can get human muscle to do the same things.”
Davis, 46, has been engaged in a multiyear quest to do just that during which he's gone into debt, mortgaged his house, scraped together government and foundation grants, and endured frozen equipment and logistical nightmares all in an effort to give people the same physical powers that Tony has. Today, he and three colleagues Ray Geor, from Michigan State; Pauline Entin, from Northern Arizona University; and Shannon Pratt, from North Carolina State are here thanks to funding from the Diabetes Action Research and Education Foundation, which wants to know more about how the dogs regulate glucose and insulin, the stuff that powers the bodies of both canine and human athletes. That work is of a piece with broader research that Davis began years ago, when the U.S. military's blue-sky science outfit, the Defense Advanced Research Projects Agency (DARPA), realized that studying sled-dog performance could help them improve the performance of human beings.
“One place that always concerned us was special-operations soldiers,” says Joe Bielitzki, a veterinary scientist and biotechnology researcher who was once in charge of DARPA's soldier-enhancement effort and now works at the University of Central Florida. The agency wanted to give an Army Ranger or Navy SEAL the ability to, say, drop into Tora Bora and perform rigorous physical feats for days on end with little sleep or rest, all while keeping his mental composure. But while DARPA knew it wanted to enhance the troops, it didn't know how.
Bielitzki was aware that some of the most radical science to affect human medicine like in vitro fertilization and cloning had roots in the world of veterinary research. So in 2003 he toured university vet schools around the country to introduce DARPA to scientists, many of whom knew nothing of the agency and its grant program.
“There was a meeting of that nature at Oklahoma State, but I was not invited to it,” Davis recalls. “I was just a wet-behind-the-ears junior faculty member.”
Davis, a burly, dark-haired guy with a cocky streak, decided to crash the meeting. “The faculty were pitching ideas to Joe, and he wasn't that impressed, because they weren't grasping the nature of DARPA, which isn't interested in incremental advances,” he says. “They want orders-of-magnitude advances. Finally, he said, 'Look, let me give you some examples of stuff we're thinking about on our own,' and one was finding a way for soldiers to operate at 50 percent of aerobic capacity for days on end. Well, then it was my turn to be unimpressed, and being young and uncouth I kinda snorted out, 'We already know how to do that.' Joe swiveled in his chair and said, 'Really?' “
DESPITE THE FACT that Tony came home just 20 minutes ago, he doesn't even look tired. He's standing on his hind legs pawing my T-shirt, shaking his muddy tail at egg-beater speed. He thinks my arrival means something exciting is about to happen, preferably another run. Right now he's willing to go out and post another 22 miles.
The fitness and desire among these dogs is legendary, but until recently little was known about how their bodies work. The first brief flurry of investigation happened back in the late sixties, when medical researchers Robert Van Citters (University of Washington) and Dean Franklin (Scripps Clinic and Research Foundation, in San Diego) began a systematic inquiry into sled-dog physiology. Using teams from Fort Wainwright, near Fairbanks, Van Citters and Franklin implanted measuring devices and flow meters inside the dogs' major blood vessels. Then they had them pull sleds for several hours along the Chena River, sometimes covering 30 miles.
If a man performed anything close to such extreme exercise, he'd have to recruit every drop of blood his body could muster, sending it through the lungs and to the muscles. That blood would be rerouted from other organs, such as the kidneys, the liver, and the gut. But that requires those organs to virtually shut down, which you can do for only so long before you start to damage them.
The dogs in Van Citters and Franklin's experiments, however, didn't have to draw blood from their gut organs, partly as a result of their incredible adaptation to training. According to Ken Hinchcliff, in just several months of workouts a dog like Tony can boost the size of his heart by 50 percent.
Van Citters and Franklin were driven by curiosity, not long-term practical application. They moved on, and nobody picked up the string until the early nineties, when Hinchcliff got involved. “I was doing my Ph.D. in exercise physiology and became interested in endurance,” he says. “I came across these dogs and thought it was fascinating. Apart from Van Citters and Franklin, there wasn't really any recent stuff. But one of the principles of physiology is that if you want to understand a system, you study the extreme expression of that system, and the sled dogs are the extreme expression of endurance exercise.”
Starting in the early nineties, Hinchcliff began traveling to Alaska to study racing dogs, often with the help of musher Rick Swenson, the only five-time winner of the Iditarod. Research performed by him and others revealed that sled dogs aren't just extreme in their aerobic capacity; they possess a variety of souped-up systems.
For example, sled-dog muscle cells are jammed with mitochondria, the energy-producing units. The dogs have about 70 percent more of them per cell than humans have.
In addition, sled dogs like all dogs and some other animals like bears don't sweat. They dissipate heat by thermal exchange through paws, noses, and tongues. People can run long distances in hot weather, unlike dogs, but our system of evaporative cooling costs us water, electrolytes, sugars, and proteins. The sled dogs conserve theirs by relying on a cool environment. The day before visiting Zirkle's dogs, I barely hung on the back of an ATV belonging to Iditarod musher Judy Currier as she took her team on an afternoon training run. The temperature was about 50 degrees Fahrenheit hot for sled dogs and every time the team came upon puddles they belly-flopped into them.
The most important difference between the dogs and people, though, may have to do with energy how sled dogs get it and how they use it. Physiologists refer to energy sources as “substrates,” and there are three basic kinds: carbohydrates, fats, and proteins. Fats have big advantages over carbs. First, they contain about twice the caloric density, so a gram of fat can supply a lot more energy than a gram of carbs. Second, they burn “cooler.” But human muscle relies primarily on glucose, a carbohydrate that's stored in muscles as glycogen, becoming glucose again when it's used. Glucose burns “hot” compared with fat. “It's like the difference between regular ethyl and nitro fuel in a hemi,” Bielitzki says. “You can use nitro once in a while, but you can't go forever without burning out the engine.”
Fast-twitch muscles like those used in sprinting tap glycogen reserves in the muscles, turning it into glucose and burning that as an organic compound called pyruvate. That burning can work anaerobically, without oxygen, which is good because people are not as aerobically efficient as dogs and our systems can't deliver that much oxygen to muscle cells. But we can't burn up all the pyruvate, so it “overflows,” leading to a buildup of lactic acid.
In other words, the human strategy for using energy becomes unsustainable much more quickly. Even at slower paces, as in a marathon, we use up the muscles' stores of glycogen in about three hours. After a day's rest, we're still depleted. Sled dogs just keep on going.
GIVING PEOPLE the powers of the Energizer Bunny is what DARPA hopes to do, but Zirkle's garage, where I've brought Tony or, rather, where Tony has dragged me doesn't look like an incubator for augmented humans. It's filled with the detritus of life in central Alaska sled runners, parkas, mukluks, fishing rods, ropes, a dried wolf pelt. The air reeks of wet dog.
Tony is sitting, wedged between my knees, though his tail is still whipping. Davis injects the hypnotic agent propofol Michael Jackson's insomnia drug of choice into one of Tony's leg veins. In seconds, he falls asleep. Davis carries him to a brown table, where Ray Geor is waiting with a biopsy needle. As Davis monitors Tony's vital signs, Geor shaves some fur away from his upper hind leg, slides in the needle, and pulls a trigger that snaps off a tiny plug of muscle. Shannon Pratt places the tissue in a small tube while Geor seals the wound with surgical glue. Later, they'll mash up the sample and look at its RNA (the stuff that relays orders from genes to the cell's protein factories), enzymes, proteins all things that might help explain how the dogs react to a single day of intense exercise. Fifteen minutes later, Tony is sitting up, a little woozy but once again wagging his tail.
The other half of the study is more difficult. Some of Tony's kennel mates will be placed in carriers, and the scientists will insert ports into their leg veins for a test called a “glucose clamp.” They'll pump glucose and a set amount of insulin through the ports to see how much glucose it takes to keep the dogs at a baseline blood-sugar level. The more glucose they can give them without zooming their blood sugar, the more “insulin sensitive” the dogs are, or the better they are at packing sugar away in their muscle cells. But performing a clamp on a hyperactive sled dog is a struggle, not least because you have to keep them still so they don't rip out the port even while you take blood-sugar readings every few minutes.
Zirkle, a former Ivy League hammer thrower who in 2000 became the first woman to win the 1,000-mile Yukon Quest, has an enormous amount of time, money, and affection invested in these dogs. Allowing Davis to poke holes in them requires trust. Establishing that trust was his first hurdle.
A native of Texas who read “too many dime-store novels about the West,” Davis grew up wanting to be the world's greatest horse vet. But while working toward his Ph.D. at Baltimore's Johns Hopkins, he got interested in respiratory problems, specifically in a condition called “exercise-induced asthma,” which can afflict both humans and horses, especially in cold weather. For a variety of reasons, his research was faltering, and he feared he'd never find a way to get the cold-weather-exercise animal data he needed. Then, in 1999, he says, “I was driving down the road and thought, Of course I can do it, because there are dogs who do it on their own all the time: sled dogs. Then I drove another half-mile and I thought, Why screw around in the lab at all? Why not do it on sled dogs in Alaska?”
At first he got nowhere. Mushers and the vets they trusted wanted no part of a stranger from the lower 48 knocking out their dogs and sliding an endoscope into their airways, especially at a time when the Iditarod was taking PR hits over dog deaths during the race. (On average, about three dogs die during each Iditarod, from causes that include heart failure, pneumonia, and sled injury.) The dog deaths, however, proved to be Davis's salvation. Necropsies on several dogs showed evidence of bleeding gastric ulcers. The mushers needed to know if the dogs were developing the ulcers while racing. The best way to find out was to anesthetize and scope them after they'd either completed or dropped out of the race. Davis offered to do the work for free if he could be allowed to scope their airways at the same time.
During the next two Iditarods, Davis and endoscopy expert Mike Willard were able to confirm that nearly half of the sled dogs developed gastric ulcers during the race but most never showed outward signs. Those findings and a recommendation by Davis and colleague Kathy Williamson to use a drug that reduces stomach acids appear to have greatly reduced the problem, so Davis won the mushers' trust.
Unfortunately for Davis, his finances were melting, because he was paying for all the research trips. “I was naive,” he recalls. “I was having fun, both as sort of an adventure doing all this stuff up in Alaska and just intellectually discovering things. It was intoxicating.” So intoxicating that he'd run up $30,000 in credit-card debt.
Then, in 2003, Davis told Bielitzki about how far and how long sled dogs can run. A few weeks later, Bielitzki issued a call for grant proposals that seemed custom-tailored for Davis. Davis and Hinchcliff pounded out a pitch, and DARPA awarded them $1.5 million and the assignment to widen what Hinchcliff calls “bottlenecks” in human performance. Davis bought a truck, a trailer to serve as a mobile lab, and started making more trips to Alaska.
YOU WOULDN'T KNOW IT to look at Tony, because he's pretty slight, but he's fed a diet that's mostly fat up to 60 percent. “You'd kill a pet dog with that,” says Erica McKenzie, a professor of large-animal medicine at Oregon State University who's studied sled dogs with Davis. If people ate such a diet, we'd all be diabetics living not for long on Lipitor.”In sled dogs we have a model where they exist continuously on a high-fat diet and are highly insulin sensitive,” says Davis. “It raises the question of whether all those associations [between fatty diets and diabetes] are just an association and not a cause and effect. Or is there something else that goes along with a high-fat diet in humans that causes insulin resistance? Or maybe there's something you can do while eating a high-fat diet that prevents you from developing insulin resistance.”
Fat, it turns out, is likely the key to the dogs' remarkable endurance.When dogs are dropped from the Iditarod, it usually happens during the first few hundred miles. Some show signs of severe fatigue and muscle soreness, just like a person would. But something allows the rest of the dogs to finish the race. Zirkle herself is amazed, she says, that her own dogs seem more eager to run when they've finished the race than they did one or two days in.In fact, as Davis and his colleagues discovered, the fittest dogs are actually able to repair themselves as the race goes on.
“You take dogs out and you run them 100 miles per day today and tomorrow and the next day, and they come back, sleep, eat, do it again without having any outward sign of it mattering,” Davis explains. “You would assume they're achieving homeostasis,” a condition of optimal operation. “You'd never think that they're at the furthest thing from homeostasis. They're damaging tissues, depleting energy stores, their oxidative stress is through the roof, and all those things are supposed to make you crater.” Yet the dogs don't crater. “What they showed us is that there is an ability to adapt to that stress in a matter of days so that it is no longer stressful,” Davis says.
Davis has seen signs that even the gastric-ulcer damage appears to be under repair by the end of a marathon race. Most important, though, the dogs rebuild their glycogen stores. It's likely that they manage this miracle by literally switching much of the fuel they use from glucose to fat. No cell burnout, no lactic-acid buildup, no long-term depletion of stored glycogen.In a journal article, Davis and colleagues used scientific understatement, calling the discovery “a novel finding.” In fact, Bielitzki recalls, the news “shocked everybody.”Nobody knows exactly how the dogs make the switch, except that the ability must be under genetic control. So the quest is on to figure out what those genetic signals are.
THE PAYOFFS TO THIS kind of research can often appear so far away that they live only in the dreams of sci-fi aficionados, but giving athletes and soldiers the abilities of sled dogs may not be as distant. The program has already had some small “deliverables,” in DARPA parlance. Stanford researchers have developed a cooling device, now marketed by a company called Avacore Technologies, that lets athletes and soldiers cool their core body temperature the way dogs do. It's being used by college football teams at Stanford and Miami and by the San Francisco 49ers. Lance Armstrong has been drinking a sports supplement based on quercetin, a plant-based flavonoid that's supposed to increase production of mitochondria.
Applying Davis's findings on how sled dogs use energy doesn't necessarily have to wait for some gene-modification breakthrough. Davis thinks it's possible humans already have some capacity to use large amounts of fat as a primary fuel. Within the next five years or so, dietary and training interventions like diets high in the right fatty acids or training methods that exploit whatever latent abilities people have to push past the initial damage stage of endurance could be developed in a way that will give humans greater ability to adapt to exercise. Once the genetic switches the dogs use to flip from carbs to fats are revealed, he tells me, people might be screened for human analogs as part of the selection process for extremely demanding sports or military duties.
According to the Army, Davis's “work is expected to provide the foundation for construction and prospective testing of appropriate training conditions for the induction [of] fatigue resistance in animals and, eventually, humans.”
None of that seems outlandish. But Bielitzki doesn't believe in thinking conservatively. He considers it likely there'll be a pill, maybe in about a decade, that will allow people to do what sled dogs do. “That was the intent,” he says. “That is still the hope.”
There's plenty of incentive. Any company that developed such a so-called small-molecule drug could attack “metabolic syndrome,” the constellation of symptoms surrounding much cardiovascular disease and diabetes. A drug like that would immediately become a global blockbuster. “We're just starting to get where molecular techniques associated with the genome and the metabolome are altered according to cues,” he says. “The next ten years are going to be a magical period. We're gonna learn a lot.”
When it happens, don't forget to thank Tony.