Today’s Lab Rats of Obesity: Furry Couch Potatoes
HILLSBORO, Ore. — Like many these days, Shiva sits around too much, eating rich, fatty foods and sipping sugary drinks. He has the pot belly to prove it, one that nearly touches the floor — when he’s on all fours, that is.
Shiva belongs to a colony of monkeys who have been fattened up to help scientists study the twin human epidemics of obesity and diabetes. The overweight monkeys also test new drugs aimed at treating those conditions.
“We are trying to induce the couch-potato style,” said Kevin L. Grove, who directs the “obese resource” at the Oregon National Primate Research Center here. “We believe that mimics the health issues we face in the United States today.”
The corpulent primates serve as useful models, experts say, because they resemble humans much more than laboratory rats do, not only physiologically but in some of their feeding habits. They tend to eat when bored, even when they are not really hungry. And unlike human subjects who are notorious for fudging their daily calorie or carbohydrate counts, a caged monkey’s food intake is much easier for researchers to count and control.
“Nonhuman primates don’t lie to you,” said Dr. Grove, who is a neuroscientist. “We know exactly how much they are eating.”
To allow monitoring of their food intake, some of the obese monkeys are kept in individual cages for months or years, which also limits their exercise. That is in contrast to most of the monkeys here who live in group indoor/outdoor cages with swings and things to climb on.
While this research is not entirely new and has been the target of some animal rights’ group complaints, demand for the overweight primates is growing as part of the battle against the nation’s obesity epidemic, according to Dr. Grove and other researchers working with such monkeys in Florida, Texas and North Carolina, and also overseas.
Some tests have already produced tangible results. Rhythm Pharmaceuticals, a start-up company in Boston, tested its experimental diet drug on some of the Oregon monkeys. After eight weeks, the animals reduced their food intake 40 percent and lost 13 percent of their weight, without apparent heart problems.
“We could get a much better readout on chronic safety and efficacy early,” said Bart Henderson, the president of Rhythm, which now plans to move into human testing.
In another study, a group of academic researchers is using the monkeys to compare gastric bypass surgery with weight loss from forced dieting. One goal is to try to figure out the hormonal mechanisms by which the surgery can quickly resolve diabetes, so that drugs might one day be developed to have the same effect. To that end, the study will do what cannot be done with people — kill some of the monkeys to examine their brains and pancreases.
The primate center here, which is part of Oregon Health and Science University, has more than 4,000 monkeys, mostly rhesus macaques. About 150 of them are the rotund rhesuses. Some receive daily insulin shots to treat diabetes, and some have clogged arteries. One monkey died of a heart attack a few years ago at a fairly young age.
Shiva, a young adult, gained about 15 pounds in six months and weighs about 45 pounds, twice the normal weight for his age. Like other monkeys with a weight problem, he carries much of the excess in his belly, not his arms and legs.
The monkey’s daily diet consists of dried chow pellets, with about one-third of the caloriescoming from fat, similar to a typical American diet, Dr. Grove said, though the diet also contains adequate protein and nutrients.
They can eat as many pellets as they want. They also snack daily on a 300-calorie chunk of peanut butter, and are sometimes treated to popcorn or peanuts. Gummy bears were abandoned because they stuck to the monkeys’ teeth.
They also drink a fruit-flavored punch with the fructose equivalent of about a can of soda a day. In all, they might consume about twice as many calories as a normal-weight monkey.
Dr. Grove and researchers at some other centers say the high-fructose corn syrup appears to accelerate the development of obesity and diabetes.
“It wasn’t until we added those carbs that we got all those other changes, including those changes in body fat,” said Anthony G. Comuzzie, who helped create an obese baboon colony at the Southwest National Primate Research Center in San Antonio.
Still, about 40 percent do not put on a lot of weight.
Barbara C. Hansen of the University of South Florida said calories, but not high fat, were important. “To suggest that humans and monkeys get fat because of a high-fat diet is not a good suggestion,” she said.
Dr. Hansen, who has been doing research on obese monkeys for four decades, prefers animals that become naturally obese with age, just as many humans do. Fat Albert, one of her monkeys who she said was at one time the world’s heaviest rhesus, at 70 pounds, ate “nothing but an American Heart Association-recommended diet,” she said.
Mice and rats remain the main animals for medical research, but the effects on rodents often do not mirror those in people.
Rinat Neuroscience had an experimental drug that sharply reduced appetite in rodents. But obese baboons in San Antonio doubled or tripled their food intake when they got the drug.
Some companies see no need to use primates to study obesity and diabetes, saying it is almost as easy to do human studies.
Monkey studies can cost up to several million dollars. The animals are so precious that only a small number can be used. And there are ethical reviews before a study can begin.
“Doing primate studies is about as difficult as doing human studies from an ethical standpoint,” said Dr. Lee M. Kaplan, director of the weight center at Massachusetts General Hospital, who is one of the researchers in the bariatric surgery study here.
Animal rights activists say primate studies subject animals to needless suffering, like the stress of being caged. Two activists got jobs here in the last decade and presented evidence of what they said were mistreated and unhealthy monkeys.
Jim Newman, a spokesman for the primate center, said the accusations were unfounded and that after both instances, inspectors from the Department of Agriculture found no violations of rules.
Activists also question whether the studies are needed.
For example, they point to studies in the last two years by Dr. Grove and colleagues showing that when pregnant monkeys ate the high-fat diet, their offspring had metabolic problems. The babies were also more prone to anxiety when confronted with threatening objects, like a Mr. Potato Head with huge eyes.
“Terrorizing Monkeys with Mr. Potato Head is Research?” Alisa Mullins of People for the Ethical Treatment of Animals wrote in November. She noted that in the study, fetuses were taken from wombs and killed so their brains could be dissected. She also questioned the need to study fat monkeys: “Gee, couldn’t he have hung out at the local McDonald’s and learned the same thing?”
Dr. Grove said he understood the protesters’ view: “I applaud them for that pressure because it makes us do our job better.”
But he said the study found the diet induced chemical changes in the brains of fetuses that might be responsible for the problems in the offspring. The findings might also apply to humans but could not be studied in people.
The studies also found something else that could be important for people — that eating a healthy diet during pregnancy reduced troubles in the offspring. That suggests, he said, that the diet of a pregnant woman matters more than whether she is obese.
He also defended keeping the animals in some studies in individual cages. Not all labs do. At Wake Forest University, the monkeys are housed in pairs and separated only at meal times so that researchers can monitor what each monkey eats.
“These are social animals,” said Janice D. Wagner, a professor of pathology there. “We think they are happier that way.”
But Dr. Grove said he needed the animals separated at all times so they could snack between meals, since that is an important reason people gain weight. And allowing them outside, even one at a time, would mean they would exercise more.
“Our research model is a sedentary lifestyle with calorically dense diets,” he said.
As pharmaceutical companies move some research to less expensive countries, the obese monkeys are following. “This is a booming industry in China,” said Dr. Grove. “They have colonies of thousands of them.”