A Pill to Make Exercise Obsolete

Nicola Twilley in The New Yorker:

It was late summer, and the gray towers of the Salk Institute, in San Diego, shaded seamlessly into ocean fog. The austere, marble-paved central courtyard was silent and deserted. The south lawn, a peaceful retreat often used for Tai Chi and yoga classes, was likewise devoid of life, but through vents built into its concrete border one could detect a slight ammoniac whiff from more than two thousand cages of laboratory rodents below. In a teak-lined office overlooking the ocean, the biologist Ron Evans introduced me to two specimens: Couch Potato Mouse and Lance Armstrong Mouse. Couch Potato Mouse had been raised to serve as a proxy for the average American. Its daily exercise was limited to an occasional waddle toward a bowl brimming with pellets of laboratory standard “Western Diet,” which consists almost entirely of fat and sugar and is said to taste like cookie dough. The mouse was lethargic, lolling in a fresh layer of bedding, rolls of fat visible beneath thinning, greasy-looking fur. Lance Armstrong Mouse had been raised under exactly the same conditions, yet, despite its poor diet and lack of exercise, it was lean and taut, its eyes and coat shiny as it snuffled around its cage. The secret to its healthy appearance and youthful energy, Evans explained, lay in a daily dose of GW501516: a drug that confers the beneficial effects of exercise without the need to move a muscle. Exercise has its discomforts, after all: as we sat down to talk, Evans, a trim sixtysomething in a striped polo shirt, removed a knee brace from a coffee table, making room for a mug of peppermint tea; he was trying to soothe his stomach, having picked up a bug while hiking in the Andes. Evans began experimenting with 516, as the drug is commonly known, in 2007. He hoped that it might offer clues about how the genes that control human metabolism are switched on and off, a question that has occupied him for most of his career.

Mice love to run, Evans told me, and when he puts an exercise wheel in their cage they typically log several miles a night. These nocturnal drills are not simply a way of dealing with the stress of laboratory life, as scientists from Leiden University, in the Netherlands, demonstrated in a charming experiment conducted a few years ago. They left a small cagelike structure containing a training wheel in a quiet corner of an urban park, under the surveillance of a motion-activated night-vision camera. The resulting footage showed that the wheel was in near-constant use by wild mice. Despite the fact that their daily activities—foraging for food, searching for mates, avoiding predators—provided a more than adequate workout, the mice voluntarily chose to run, spending up to eighteen minutes at a time on the wheel, and returning for repeat sessions. (Several frogs and slugs also made use of the amenity, possibly by accident.)

Still, as the example of Lance Armstrong Human makes clear, sometimes exercise alone is not enough. When Evans began giving 516 to laboratory mice that regularly used an exercise wheel, he found that, after just four weeks on the drug, they had increased their endurance—how far they could run, and for how long—by as much as seventy-five per cent. Meanwhile, their waistlines (“the cross-sectional area,” in scientific parlance) and their body-fat percentage shrank; their insulin resistance came down; and their muscle-composition ratio shifted toward so-called slow-twitch fibres, which tire slowly and burn fat, and which predominate in long-distance runners. In human terms, this would be like a Fun-Run jogger waking up with the body of Mo Farah. Evans published his initial results in the journal Cell, in 2008. This year, he showed that, if his cookie-dough-scarfing mice were allowed to exercise, the ones that had been given 516 for eight weeks could run for nearly an hour and half longer than their drug-free peers. “We can replace training with a drug,” he said.

More here.