The Ethics of Exercise Pills

In his 1932 novel Brave New World, Aldous Huxley described a fictional drug called Soma. In the novel, a soma was something akin to an opiate, which ensured state-mandated happiness in Huxley's cautionary tale against fascist overrule and too much technology. It's the “ideal pleasure drug,” he wrote. “All of the advantages of Christianity and alcohol; none of their defects.”

Thankfully our government doesn't enforce mass euphoria to keep us quiet. But we're pretty good at exploiting scientific progress on our own. In the U.S., misuse and overuse of opiates like oxycodone and hydrocodone is rampant, and only one example of the abuse of otherwise helpful therapies. And around the corner is a class of drug that raises new dystopian red flags. I’m talking about “exercise pills,” medications intended to mimic the benefits of exercise, without, well, the exercise.

As we’ve all been told many times by now, regular physical activity benefits the body and brain in many ways. It improves fat metabolism; it encourages the development of more slow-twitch muscle fibers, or those associated with endurance; it also spurs the production of blood vessels and mitochondria, the kidney-shaped energy-producing organelles scattered around our cells that science teachers everywhere call “the powerhouses of the cell.” Researchers are now testing compounds that would deliver these benefits in pill form, on animals, and humans could be next.

A paper published last week in Trends in Pharmacological Sciences reviews the gamut of promising exercise-aping compounds, reflecting that the key to developing an effective exercise pill is tapping into these various systems of the body.

One candidate drug is AICAR. Initially developed to prevent heart injury during surgery, recent findings in mice show that the molecule increases the expression of genes that code for proteins involved in oxygen metabolism and running endurance by 44 percent. Other compounds with names like GW501516, GSK4716, and SR9009 appear to confer similar benefits in rodents, while a drug called irisin may induce the burning of stored fat. One study reported that just 10 days of treatment with the drug resulted in significant weight loss in obese mice.

The paper’s co-author Ismail Laher, a pharmacology professor at the University of British Columbia in Vancouver, says these exercise pills could hold particular promise for the disabled. “For example,” he explains, “A pill for people with spinal cord injury could be very appealing given the difficulties that these individuals face in exercising.”

Citing the explosion in obesity and diabetes in the U.S., Laher speculates that exercise pills may also help address a problem faced by many healthcare providers—that a lot of people just really don’t want to exercise. Many studies, including a 2012 report by the European Society of Cardiology, suggest that while the vast majority of people recognize the importance of physical activity in maintaining health, only somewhere between 23 percent and 40 percent of us will actually stick with an exercise regimen long-term.

Another study published in Cell Metabolism, and conducted by a group at the University of Sydney in collaboration with Danish researchers, identified nearly 1000 molecular changes that occur in the body as a result of intense physical activity, all of which represent potential targets in mimicking the physiologic effects of exercise.

“The potential here is massive,” says David James of the University of Sydney, who led the study. “One pill that targets multiple pathways is the dream.” And it may remain a dream for some time. Laher acknowledges that developing one drug that mimics all the benefits of exercise would be incredibly complicated and not likely any time soon. Beyond just muscular benefits and improved energy metabolism, exercise confers a host of health benefits, like increased bone strength, improved cognition, and help in fending off depression and anxiety.

“For now we will most likely target specific pathways,” explains Laher. “It is unrealistic to expect that exercise pills will fully be able to substitute for physical exercise—at least not in the immediate future."

The bioethicist Art Caplan agrees, and cautions against too much enthusiasm, as human data are still a ways off and many of the compounds come with side effects—including, in some cases, increased cancer risk—that may not fly in humans. He and Laher also acknowledge that these compounds are ripe for abuse. In 2013 the World Anti-Doping Agency (WADA) published a report on its Website warning of the health risks associated with GW501516. That same year a Russian cyclist was caught doping with the drug, as was another Russian athlete a year later, looking for a leg up in the surprisingly cutthroat world of competitive race-walking.

“At the end of the day these drugs will have to be carefully managed and sports doping is certainly a risk,” says James, “But this is the case for many drugs out there so I doubt they’ll make the problem any worse.”

More concerning might be general societal interest.

“If people say ‘Hey, now I can eat more chips and play more video games because I have this pill’—which they will—I suspect we won't advance the ball very much,” Caplan says. “If you install seat belts and airbags in cars people drive faster. They end up being at the same degree of risk.”

“These medications have life-changing potential for some people,” Caplan continued. “I just think they should be introduced gradually so that populations who really can’t exercise might see the benefits while harm to the general population can be minimized.”

Lest we end up stuck to the sofa. Hooked on pills. Stoned on Soma.