On October 6th, I find myself in the gleaming office of a Boston biotech. I've been seated in a clear plastic chair, where I am about to try an experimental medicine for a brain disorder I don't have.
The space is home to PureTech Ventures, the parent company of Akili Interactive Labs, which makes the new medicine. Since December, children in Florida and North Carolina have also tried the treatment as part of a formal clinical trial for attention-deficit hyperactivity disorder (ADHD). The medicine is unusual because of its delivery system: an iPad or iPhone. That's because the medication is a video game called Project: EVO.
Until now, I haven't touched a video game since about 1991. What if I fumble the mechanics, or worse — what if the game deems me cognitively deficient? One of Akili's founders, 32-year-old Eddie Martucci, hands me an iPad and I see my avatar: a yellow humanoid, floating on a jet-fueled raft down a crooked, icy river. My task seems simple: I tap on blue fish that zoom overhead, but avoid the red and green fish, as well as blue birds. Of course, I'm also steering the raft to avoid frozen spikes along the riverbank.
It's hard. It feels like I'm constantly missing my targets and smashing into the sides. Most frustrating — and addictive — of all: as I get better, the game instantly gets harder.
If Akili's clinical studies are successful, doctors will one day prescribe EVO for ADHD as well as a variety of other disorders affecting so-called executive function — the ability to plan, inhibit actions, and quickly switch between tasks. The game has been part of a dozen clinical trials to date, involving people with ADHD, Alzheimer's, autism, and depression.
The plan is realistic enough that Big Pharma wants in: Akili has already struck deals with two traditional drug companies, Pfizer and Shire. Within the industry, Martucci says, "there's definitely a growing receptivity to digital technology."
Over the past few years, a torrent of studies on video games and brain function have spurred a booming consumer market. The "digital brain health" industry reportedly grew from $600 million in annual revenues in 2009 to more than $1 billion in 2012; the biggest players are names like Lumosity, Cogmed, Posit Science, CogniFit, and Brain Resource.
But most companies aren't making medical claims; they haven't done the trials necessary for that. And what's more, scientists have said that these games promise quick-fixes they can't deliver.
In contrast, Akili is navigating through clinical trials required for EVO to become an FDA-approved medical device. If they make it, they'll have access to a completely untapped market: patients. "We don't see other people playing in that space," says Akili co-founder Eric Elenko. "From a business perspective it represents a more lucrative opportunity."
THEY'LL HAVE ACCESS TO A COMPLETELY UNTAPPED MARKET: PATIENTS
The drugs used to treat brain disorders don't just have side-effects; they usually don't address executive dysfunction. That's because drugs don't have feedback loops that aid learning, according to Adam Gazzaley, a neuroscientist at the University of California, San Francisco. "Drugs are relatively blunt instruments," he says. "They're not selective for networks and circuits in the brain."
Gazzaley got interested in scientific gaming around 2008, while conducting brain-scanning studies aimed at executive function. He wondered whether training people could improve their everyday executive function skills. But his laboratory tasks were boring; getting volunteers to play them for hours was a "preposterous" idea, he recalls.
So Gazzaley got in touch with his friend Matt Omernick, a game designer at LucasArts who was working on Star Wars: The Force Unleashed. The duo, along with other engineers and researchers, had evening get-togethers to talk about how to translate the lab's tasks into something fun. "He'd feed us sushi and beer and we would brainstorm," Omernick says.
The result was NeuroRacer, in which players steer a car along a curvy highway while responding to pop-up signs. Last year Gazzaley made the cover of Nature with a study testing senior citizens' performance on the game. At first, the seniors were horrible at it. After a month of training, they were better than untrained 20-year-olds. More important, though: their scores on untrained skills, such as sustained attention and working memory, went way up — and remained strong for at least six months. By using scalp electrodes to measure participants' brain waves, the researchers also showed that NeuroRacer training altered participants' wave patterns: the older brains looked decidedly younger.
Design-wise, NeuroRacer is like something I might have played on my Compaq 486. "I hesitate to even call it a game, it's so simplistic," Omernick says. It did have one innovative feature: its difficulty adapted in real time. Most video games get harder as a player progresses through different levels, but Omernick says NeuroRacer was the first to update on the fly.
While working on NeuroRacer, Gazzaley and Omernick met Martucci and Elenko; together they founded Akili. The company licensed NeuroRacer's algorithm; and Omernick overhauled the design to create Project: EVO.
The most important part of EVO's design, Omernick says, was making it appealing for a wide array of players, from a 7-year-old with ADHD who loves video games to an 82-year-old grandparent who's never touched a tablet. "We had to create something universally appealing that people weren't going to be intimidated by," he says. That meant no weapons and no deaths.
"WE HAD TO CREATE SOMETHING UNIVERSALLY APPEALING THAT PEOPLE WEREN'T GOING TO BE INTIMIDATED BY."
The engineers also made EVO even more adaptive than NeuroRacer, capturing performance data 30 times a second. "People are never in a spot that's either too hard or too easy for them," Martucci says. "You just literally hand the iPad to a patient and it works."
Shire — the world's largest seller of ADHD drugs — invested an undisclosed amount in Akili early on and helped design its ongoing ADHD study. The trial enrolled 80 children ages 8 to 12; half have ADHD and the other half are cognitively normal. All will play EVO for about 30 minutes a day for a month.
The goal is to see whether there's any difference between the ADHD group and controls on the game's metrics. In particular, the researchers want to study multitasking, which is what happens when participants must both steer and tap on birds. Multitasking is cognitively draining and some groups have a hard time with it; the Akili team believes they'll find a multitasking deficit in kids with ADHD. The trial's results will come sometime in 2015.
If that trial — about midway through the regulatory process for medical devices — finds a difference between the ADHD group and controls, then Akili will move on to a larger and more rigorous 'pivotal trial', testing the game against a placebo.
The clinical trials mean Akili also has to worry about EVO's side-effects, notes Stephen Faraone, a professor of psychiatry at SUNY Upstate Medical University who's consulted with Akili. Boys with ADHD or autism, he points out, have an increased risk of problematic use of video games, spending more hours playing them and having trouble disengaging. (For the ADHD trial, EVO is programmed to automatically shut off after 45 minutes.) But the game format might make children less likely to avoid taking their medicine. "It's a treatment that children will want to do," Faraone says.
Children with ADHD are more at-risk for problematic use of video games
The video-game approach makes sense based on what we know about brain circuits that are affected in ADHD, says Chandra Sripada, an assistant professor at the University of Michigan, who isn't involved with Akili. Brain imaging studies from his lab and others have shown that people with ADHD have glitches in areas involved in cognitive control, leading to an inability to stifle impulses to blurt out inappropriate words or act without thinking."The idea that these games would train the very same circuits that are weak in ADHD is very plausible," Sripada says.
Even if EVO doesn't turn out to be an effective treatment for brain disorders, it may be useful in other ways. Pfizer is funding a 100-person clinical trial to see if EVO data can be used to find markers for healthy elderly people who develop Alzheimer's disease. Currently there's no good way to predict who will get sick. The goal of the trial is to see whether Akili's game might be used as a biomarker in future clinical trials of Alzheimer's treatments, says Dean Mastrojohn, a Pfizer spokesman.
pfizer is funding a 100-person clinical trial in alzheimer's disease
Elenko and Martucci gave me a peek at my data from the 15 minutes or so that I played EVO. Happily, my 30-year-old attention skills are far better than I thought they were. I have a multitasking deficit of about 5 percent, which Martucci assured me is "extremely low" for EVO — my scores were similar to those of healthy people in their 20s.
If EVO is approved by the FDA, it will be fascinating to see how its use compares to a traditional pharmaceutical. How will doctors determine dosage? Will regular consumers like me need a prescription to get it? Will there be an over-the-counter version? Though Akili is focused on the patient market, I would be surprised if it didn't eventually cross over into the giant consumer market of cognitive enhancement. On my long train ride home from Boston, as I play 2048 on my phone again and again and again, I find myself wishing I had EVO instead.