The dangers of using one lab animal to study every disease.
Mattson was lecturing on a research program that he'd been conducting since 1995, on whether a strict diet can help ward off brain damage and disease. He'd generated some dramatic data to back up the theory: If you put a rat on a limited feeding schedule—depriving it of food every other day—and then blocked off one of its cerebral arteries to induce a stroke, its brain damage would be greatly reduced. The same held for mice that had been engineered to develop something like Parkinson's disease: Take away their food, and their brains stayed healthier.
How would these findings apply to humans, asked someone in the audience. Should people skip meals, too? At 5-foot-7 and 125 pounds, Mattson looks like a meal-skipper, and he is one. Instead of having breakfast or lunch, he takes all his food over a period of a few hours each evening—a bowl of steamed cabbage, a bit of salmon, maybe some yogurt. It's not unlike the regime that appears to protect his lab animals from cancer, stroke, and neurodegenerative disease. "Why do we eat three meals a day?" he asks me over the phone, not waiting for an answer. "From my research, it's more like a social thing than something with a basis in our biology.
But Mattson wasn't so quick to prescribe his stern feeding schedule to the crowd in Atlanta. He had faith in his research on diet and the brain but was beginning to realize that it suffered from a major complication. It might well be the case that a mouse can be starved into good health—that a deprived and skinny brain is more robust than one that's well-fed. But there was another way to look at the data. Maybe it's not that limiting a mouse's food intake makes it healthy, he thought; it could be that not limiting a mouse's food makes it sick. Mattson's control animals—the rodents that were supposed to yield a normal response to stroke and Parkinson's—might have been overweight, and that would mean his baseline data were skewed.
"I began to realize that the ‘control’ animals used for research studies throughout the world are couch potatoes," he tells me. It's been shown that mice living under standard laboratory conditions eat more and grow bigger than their country cousins. At the National Institute on Aging, as at every major research center, the animals are grouped in plastic cages the size of large shoeboxes, topped with a wire lid and a food hopper that's never empty of pellets. This form of husbandry, known as ad libitum feeding, is cheap and convenient since animal technicians need only check the hoppers from time to time to make sure they haven’t run dry. Without toys or exercise wheels to distract them, the mice are left with nothing to do but eat and sleep—and then eat some more.
That such a lifestyle would make rodents unhealthy, and thus of limited use for research, may seem obvious, but the problem appears to be so flagrant and widespread that few scientists bother to consider it. Ad libitum feeding and lack of exercise are industry-standard for the massive rodent-breeding factories that ship out millions of lab mice and rats every year and fuel a $1.1-billion global business in living reagents for medical research. When Mattson made that point in Atlanta, and suggested that the control animals used in labs were sedentary and overweight as a rule, several in the audience gasped. His implication was clear: The basic tool of biomedicine—and its workhorse in the production of new drugs and other treatments—had been transformed into a shoddy, industrial product. Researchers in the United States and abroad were drawing the bulk of their conclusions about the nature of human disease—and about Nature itself—from an organism that's as divorced from its natural state as feedlot cattle or oven-stuffer chickens.