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Would You Take An Exercise Pill?

Lazy but want to stay in shape? You may soon be able to have it both ways, thanks to a new pill in testing from GlaxoSmithKline. 

Wikicommons, W.carter


Since humans began ingesting nutrients and medicines in pill form, the possibility of fixing every problem via this mechanism has tantalized the imagination. Depressed? Angry? Unable to focus? Sexually dysfunctional? Someone, somewhere has a pill for that. How about a pill that will exercise for you? 

Okay, that’s not quite how it works, but the idea of providing the same physiological mechanisms of exercise—namely, cardiovascular health and weight loss—by swallowing a pill is closer than you might think. 

One pill in particular (GW501516) mimics the effects of endurance exercise on the gene PPAR-delta. When 516 binds to this gene it boosts a signal to burn fat. So far this experiment is working in two mice, dubbed Couch Potato Mouse and Lance Armstrong Mouse. 

These mice are residents of San Diego’s Salk Institute, where both enjoy a plentiful diet of a fat-sugar mix that tastes like cookie dough. Both rodents are also sedentary; Lance isn’t out huffing it on a wheel all day. The only difference is that Couch Potato does not get his daily 516, which is why he’s fat and greasy. Lance, by contrast, exhibits tons of energy while maintaining a sleek figure. 

516 was initially created by GlaxoSmithKline when chemical biologist Tim Wilson was looking for ways to treat diabetics. Initial results on obese monkeys showed an increase in good cholesterol and a reduction in bad cholesterol, insulin levels, and triglycerides. At the time Wilson believed he stumbled upon a metabolic syndrome wonderdrug. 

His hopes held until 2007, when the pharmaceutical giant shelved 516 as long-term toxicity effects started rolling in. Animal studies showed evidence of rapidly developing cancers in a number of organs. Without a seventy-year trial the company was concerned the FDA would not feel the consequences were worth lower cholesterol. 

Cue fitness fanatics. Around the time 516 was being shelved, molecular and developmental biologist Ron Evans started injecting the above mice. Though the World Anti-Doping Agency (WADA) banned 516 in 2009, steroid message boards are filled with anecdotal test cases, in part due to evidence from Evans’s lab. The drug prevents you from “hitting the wall” too soon due to a boost in your reserves of adenosine triphosphate (ATP). With a bit of tweaking Evans hopes this switch becomes genetically encoded: 

We proved that endurance could be genetically engineered through this particular switch. And the switch stayed on, and could be passed on as a genetic trait. You could have a whole lineage of long-distance-running mice.

Even without actually running, the mice remain svelte and energized. Could it work in humans? Evans is responsible for letting WADA in on his research before his famous study, published in the journal Cell, set the Internet on fire. Cycling and running competitors were monitored, but not the ripped dude snapping shirtless selfies in the gym. For roughly $1,000 per ten grams ungodly bursts of endurance arrive packaged at your door. 

Which is, in many ways, what Evans wants: a genetic enhancement that makes you last longer while growing stronger. What of those whose goal is to binge on The Deuce while shoveling in pints of cookie dough ice cream? We’re already attuned to expecting instant gratification for as little work possible. What if no work provides even better benefits? 

The seduction of quick results combined with a lack of foresight regarding potentially crippling effects has undone our fantasies time and again. This is our genetic inheritance, an ongoing battle between energy conservation and nomadic wandering. Since we no longer need to hunt, conservation wins out. We have to motivate ourselves to put in the work to stay healthy.

Which is quite easy for some, sometimes to unhealthy degrees. “Chronic cardio” is one example of trim waistline obsessed gym rats. Pills like 516 and others—there are a number of others coming down the pipeline—might get you that extra mile on training day, but it could also get you to skip every mile. It’s hard to see the benefit of not moving at all, given the evolutionary necessity of movement. But if rocking rock-hard abs for your million Instagram followers is possible without the planks and HIIT, we’d be fooling ourselves if believing many won’t try.

To counteract sedentary habits the fitness industry now has $3 trillion in assets worldwide. Every year American health clubs rake in $27 billion from 55 million members. Sure, Planet Fitness counts on you not going for its success, but many take fitness seriously. Endurance pills might appeal to both ends: those looking to push their workouts to the next level and those who would rather just enjoy the free pizza at the front desk. 

How to navigate these unchartered waters? University of California, Riverside biologist Theodore Garland suggests an ideal solution. Instead of designing drugs to replace exercise, or even to enhance it, how about a pill getting you on the treadmill or swinging a kettlebell in the first place? 

Personally, I’ve been more interested in the possibility of drugs that would make us more motivated to exercise.

We can’t stop the exercise pills. They appeal to too many people brought up on too many science fiction tales. 516 might not survive clinical scrutiny, but given the complete lack of oversight of nutritional supplements such self-prescribed performance enhancers will soon be as common as green tea and acai weight-loss pills. 

A little boost is not necessarily bad—caffeine is my pre-workout and pre-writing ritual. Before the onslaught begins, though, we should at least understand the costs. A few years of increased endurance aren’t worth a complete lack of it in the end. 

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Derek is the author of Whole Motion: Training Your Brain and Body For Optimal Health. Based in Los Angeles, he is working on a new book about spiritual consumerism. Stay in touch on Facebook and Twitter.

Neom, Saudi Arabia's $500 billion megacity, reaches its next phase

Construction of the $500 billion dollar tech city-state of the future is moving ahead.

Credit: Neom
Technology & Innovation
  • The futuristic megacity Neom is being built in Saudi Arabia.
  • The city will be fully automated, leading in health, education and quality of life.
  • It will feature an artificial moon, cloud seeding, robotic gladiators and flying taxis.
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Human brains remember certain words more easily than others

A study of the manner in which memory works turns up a surprising thing.

Image Point Fr / Shutterstock
Mind & Brain
  • Researchers have found that some basic words appear to be more memorable than others.
  • Some faces are also easier to commit to memory.
  • Scientists suggest that these words serve as semantic bridges when the brain is searching for a memory.

Cognitive psychologist Weizhen Xie (Zane) of the NIH's National Institute of Neurological Disorders and Stroke (NINDS) works with people who have intractable epilepsy, a form of the disorder that can't be controlled with medications. During research into the brain activity of patients, he and his colleagues discovered something odd about human memory: It appears that certain basic words are consistently more memorable than other basic words.

The research is published in Nature Human Behaviour.

An odd find

Image source: Tsekhmister/Shutterstock

Xie's team was re-analyzing memory tests of 30 epilepsy patients undertaken by Kareem Zaghloul of NINDS.

"Our goal is to find and eliminate the source of these harmful and debilitating seizures," Zaghloul said. "The monitoring period also provides a rare opportunity to record the neural activity that controls other parts of our lives. With the help of these patient volunteers we have been able to uncover some of the blueprints behind our memories."

Specifically, the participants were shown word pairs, such as "hand" and "apple." To better understand how the brain might remember such pairings, after a brief interval, participants were supplied one of the two words and asked to recall the other. Of the 300 words used in the tests, five of them proved to be five times more likely to be recalled: pig, tank, doll, pond, and door.

The scientists were perplexed that these words were so much more memorable than words like "cat," "street," "stair," "couch," and "cloud."

Intrigued, the researchers looked at a second data source from a word test taken by 2,623 healthy individuals via Amazon's Mechanical Turk and found essentially the same thing.

"We saw that some things — in this case, words — may be inherently easier for our brains to recall than others," Zaghloul said. That the Mechanical Turk results were so similar may "provide the strongest evidence to date that what we discovered about how the brain controls memory in this set of patients may also be true for people outside of the study."

Why understanding memory matters

person holding missing piece from human head puzzle

Image source: Orawan Pattarawimonchai/Shutterstock

"Our memories play a fundamental role in who we are and how our brains work," Xie said. "However, one of the biggest challenges of studying memory is that people often remember the same things in different ways, making it difficult for researchers to compare people's performances on memory tests." He added that the search for some kind of unified theory of memory has been going on for over a century.

If a comprehensive understanding of the way memory works can be developed, the researchers say that "we can predict what people should remember in advance and understand how our brains do this, then we might be able to develop better ways to evaluate someone's overall brain health."

Party chat

Image source: joob_in/Shutterstock

Xie's interest in this was piqued during a conversation with Wilma Bainbridge of University of Chicago at a Christmas party a couple of years ago. Bainbridge was, at the time, wrapping up a study of 1,000 volunteers that suggested certain faces are universally more memorable than others.

Bainbridge recalls, "Our exciting finding is that there are some images of people or places that are inherently memorable for all people, even though we have each seen different things in our lives. And if image memorability is so powerful, this means we can know in advance what people are likely to remember or forget."

spinning 3D model of a brain

Temporal lobes

Image source: Anatomography/Wikimedia

At first, the scientists suspected that the memorable words and faces were simply recalled more frequently and were thus easier to recall. They envisioned them as being akin to "highly trafficked spots connected to smaller spots representing the less memorable words." They developed a modeling program based on word frequencies found in books, new articles, and Wikipedia pages. Unfortunately, the model was unable to predict or duplicate the results they saw in their clinical experiments.

Eventually, the researchers came to suspect that the memorability of certain words was linked to the frequency with which the brain used them as semantic links between other memories, making them often-visited hubs in individuals's memory networks, and therefore places the brain jumped to early and often when retrieving memories. This idea was supported by observed activity in participants' anterior temporal lobe, a language center.

In epilepsy patients, these words were so frequently recalled that subjects often shouted them out even when they were incorrect responses to word-pair inquiries.

Seek, find

Modern search engines no longer simply look for raw words when resolving an inquiry: They also look for semantic — contextual and meaning — connections so that the results they present may better anticipate what it is you're looking for. Xie suggests something similar may be happening in the brain: "You know when you type words into a search engine, and it shows you a list of highly relevant guesses? It feels like the search engine is reading your mind. Well, our results suggest that the brains of the subjects in this study did something similar when they tried to recall a paired word, and we think that this may happen when we remember many of our past experiences."

He also notes that it may one day be possible to leverage individuals' apparently wired-in knowledge of their language as a fixed point against which to assess the health of their memory and brain.

Does conscious AI deserve rights?

If machines develop consciousness, or if we manage to give it to them, the human-robot dynamic will forever be different.

Videos
  • Does AI—and, more specifically, conscious AI—deserve moral rights? In this thought exploration, evolutionary biologist Richard Dawkins, ethics and tech professor Joanna Bryson, philosopher and cognitive scientist Susan Schneider, physicist Max Tegmark, philosopher Peter Singer, and bioethicist Glenn Cohen all weigh in on the question of AI rights.
  • Given the grave tragedy of slavery throughout human history, philosophers and technologists must answer this question ahead of technological development to avoid humanity creating a slave class of conscious beings.
  • One potential safeguard against that? Regulation. Once we define the context in which AI requires rights, the simplest solution may be to not build that thing.

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