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The human mind can be a confusing and overwhelming place. Despite incredible leaps in human progress, many of us still struggle to make our peace with our thoughts. The roots of this are complex and multifaceted. To find explanations for the global mental health epidemic, one can tap into neuroscience, psychology, evolutionary biology, or simply observe the meaningless systems that dominate our modern-day world.
This is not only the context of our reality but also that of the critically-acclaimed Netflix series, Maniac. Psychological dark comedy meets science fiction, Maniac is a retro, futuristic, and hallucinatory trip that is filled with hidden symbols. Directed by Cary Joji Fukunaga, the series tells the story of two strangers who decide to participate in the final stage of a “groundbreaking” pharmaceutical trial—one that combines novel pharmaceuticals with artificial intelligence, and promises to make their emotional pain go away.
Naturally, things don’t go according to plan.
From exams used for testing defense mechanisms to techniques such as cognitive behavioral therapy, the narrative infuses genuine psychological science. As perplexing as the series may be to some viewers, many of the tools depicted actually have a strong grounding in current technological advancements.
Catalysts for Alleviating Suffering
In the therapy of Maniac, participants undergo a three-day trial wherein they ingest three pills and appear to connect their consciousness to a superintelligent AI. Each participant is hurled into the traumatic experiences imprinted in their subconscious and forced to cope with them in a series of hallucinatory and dream-like experiences.
Perhaps the most recognizable parallel that can be drawn is with the latest advancements in psychedelic therapy. Psychedelics are a class of drugs that alter the experience of consciousness, and often cause radical changes in perception and cognitive processes.
Through a process known as transient hypofrontality, the executive “over-thinking” parts of our brains get a rest, and deeper areas become more active. This experience, combined with the breakdown of the ego, is often correlated with feelings of timelessness, peacefulness, presence, unity, and above all, transcendence.
Despite being not addictive and extremely difficult to overdose on, regulators looked down on the use of psychedelics for decades and many continue to dismiss them as “party drugs.” But in the last few years, all of this began to change.
Earlier this summer, the FDA granted breakthrough therapy designation to MDMA for the treatment of PTSD, after several phases of successful trails. Similar research has discovered that Psilocybin (also known as magic mushrooms) combined with therapy is far more effective than traditional forms of treatment to treat depression and anxiety. Today, there is a growing and overwhelming body of research that proves that not only are psychedelics such as LSD, MDMA, or Psylicybin effective catalysts to alleviate suffering and enhance the human condition, but they are potentially the most effective tools out there.
It’s important to realize that these substances are not solutions on their own, but rather catalysts for more effective therapy. They can be groundbreaking, but only in the right context and setting.
In Maniac, the medication-assisted therapy is guided by what appears to be a super-intelligent form of artificial intelligence called the GRTA, nicknamed Gertie. Gertie, who is a “guide” in machine form, accesses the minds of the participants through what appears to be a futuristic brain-scanning technology and curates customized hallucinatory experiences with the goal of accelerating the healing process.
Such a powerful form of brain-scanning technology is not unheard of. Current levels of scanning technology are already allowing us to decipher dreams and connect three human brains, and are only growing exponentially. Though they are nowhere as advanced as Gertie (we have a long way to go before we get to this kind of general AI), we are also seeing early signs of AI therapy bots, chatbots that listen, think, and communicate with users like a therapist would.
The parallels between current advancements in mental health therapy and the methods in Maniac can be startling, and are a testament to how science fiction and the arts can be used to explore the existential implications of technology.
Not Necessarily a Dystopia
While there are many ingenious similarities between the technology in Maniac and the state of mental health therapy, it’s important to recognize the stark differences. Like many other blockbuster science fiction productions, Maniac tells a fundamentally dystopian tale.
The series tells the story of the 73rd iteration of a controversial drug trial, one that has experienced many failures and even led to various participants being braindead. The scientists appear to be evil, secretive, and driven by their own superficial agendas and deep unresolved emotional issues.
In contrast, clinicians and researchers are not only required to file an “investigational new drug application” with the FDA (and get approval) but also update the agency with safety and progress reports throughout the trial.
Furthermore, many of today’s researchers are driven by a strong desire to contribute to the well-being and progress of our species. Even more, the results of decades of research by organizations like MAPS have been exceptionally promising and aligned with positive values. While Maniac is entertaining and thought-provoking, viewers must not forget the positive potential of such advancements in mental health therapy.
Science, technology, and psychology aside, Maniac is a deep commentary on the human condition and the often disorienting states that pain us all. Within any human lifetime, suffering is inevitable. It is the disproportionate, debilitating, and unjust levels of suffering that we ought to tackle as a society. Ultimately, Maniac explores whether advancements in science and technology can help us live not a life devoid of suffering, but one where it is balanced with fulfillment.
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“The Six Ds are a chain reaction of technological progression, a road map of rapid development that always leads to enormous upheaval and opportunity.”
–Peter Diamandis and Steven Kotler, Bold
We live in incredible times. News travels the globe in an instant. Music, movies, games, communication, and knowledge are ever-available on always-connected devices. From biotechnology to artificial intelligence, powerful technologies that were once only available to huge organizations and governments are becoming more accessible and affordable thanks to digitization.
The potential for entrepreneurs to disrupt industries and corporate behemoths to unexpectedly go extinct has never been greater.
One hundred or fifty or even twenty years ago, disruption meant coming up with a product or service people needed but didn’t have yet, then finding a way to produce it with higher quality and lower costs than your competitors. This entailed hiring hundreds or thousands of employees, having a large physical space to put them in, and waiting years or even decades for hard work to pay off and products to come to fruition.
“Technology is disrupting traditional industrial processes, and they’re never going back.”
But thanks to digital technologies developing at exponential rates of change, the landscape of 21st-century business has taken on a dramatically different look and feel.
The structure of organizations is changing. Instead of thousands of employees and large physical plants, modern start-ups are small organizations focused on information technologies. They dematerialize what was once physical and create new products and revenue streams in months, sometimes weeks.
It no longer takes a huge corporation to have a huge impact.
Technology is disrupting traditional industrial processes, and they’re never going back. This disruption is filled with opportunity for forward-thinking entrepreneurs.
The secret to positively impacting the lives of millions of people is understanding and internalizing the growth cycle of digital technologies. This growth cycle takes place in six key steps, which Peter Diamandis calls the Six Ds of Exponentials: digitization, deception, disruption, demonetization, dematerialization, and democratization.
According to Diamandis, cofounder and chairman of Singularity University and founder and executive chairman of XPRIZE, when something is digitized it begins to behave like an information technology.
Newly digitized products develop at an exponential pace instead of a linear one, fooling onlookers at first before going on to disrupt companies and whole industries. Before you know it, something that was once expensive and physical is an app that costs a buck.
Newspapers and CDs are two obvious recent examples. The entertainment and media industries are still dealing with the aftermath of digitization as they attempt to transform and update old practices tailored to a bygone era. But it won’t end with digital media. As more of the economy is digitized—from medicine to manufacturing—industries will hop on an exponential curve and be similarly disrupted.
Diamandis’s 6 Ds are critical to understanding and planning for this disruption.
The 6 Ds of Exponential Organizations are Digitized, Deceptive, Disruptive, Demonetized, Dematerialized, and Democratized.
Diamandis uses the contrasting fates of Kodak and Instagram to illustrate the power of the six Ds and exponential thinking.
Kodak invented the digital camera in 1975, but didn’t invest heavily in the new technology, instead sticking with what had always worked: traditional cameras and film. In 1996, Kodak had a $28 billion market capitalization with 95,000 employees.
But the company didn’t pay enough attention to how digitization of their core business was changing it; people were no longer taking pictures in the same way and for the same reasons as before.
After a downward spiral, Kodak went bankrupt in 2012. That same year, Facebook acquired Instagram, a digital photo sharing app, which at the time was a startup with 13 employees. The acquisition’s price tag? $1 billion. And Instagram had been founded only 18 months earlier.
The most ironic piece of this story is that Kodak invented the digital camera; they took the first step toward overhauling the photography industry and ushering it into the modern age, but they were unwilling to disrupt their existing business by taking a risk in what was then uncharted territory. So others did it instead.
The same can happen with any technology that’s just getting off the ground. It’s easy to stop pursuing it in the early part of the exponential curve, when development appears to be moving slowly. But failing to follow through only gives someone else the chance to do it instead.
The Six Ds are a road map showing what can happen when an exponential technology is born. Not every phase is easy, but the results give even small teams the power to change the world in a faster and more impactful way than traditional business ever could.
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On a dark night, away from city lights, the stars of the Milky Way can seem uncountable. Yet from any given location no more than 4,500 are visible to the naked eye. Meanwhile, our galaxy has 100–400 billion stars, and there are even more galaxies in the universe.
The numbers of the night sky are humbling. And they give us a deep perspective…on drugs.
Yes, this includes wow-the-stars-are-freaking-amazing-tonight drugs, but also the kinds of drugs that make us well again when we’re sick. The number of possible organic compounds with “drug-like” properties dwarfs the number of stars in the universe by over 30 orders of magnitude.
Next to this multiverse of possibility, the chemical configurations scientists have made into actual medicines are like the smattering of stars you’d glimpse downtown.
But for good reason.
Exploring all that potential drug-space is as humanly impossible as exploring all of physical space, and even if we could, most of what we’d find wouldn’t fit our purposes. Still, the idea that wonder drugs must surely lurk amid the multitudes is too tantalizing to ignore.
Which is why, Alex Zhavoronkov said at Singularity University’s Exponential Medicine in San Diego last week, we should use artificial intelligence to do more of the legwork and speed discovery. This, he said, could be one of the next big medical applications for AI.
Dogs, Diagnosis, and Drugs
Zhavoronkov is CEO of Insilico Medicine and CSO of the Biogerontology Research Foundation. Insilico is one of a number of AI startups aiming to accelerate drug discovery with AI.
In recent years, Zhavoronkov said, the now-famous machine learning technique, deep learning, has made progress on a number of fronts. Algorithms that can teach themselves to play games—like DeepMind’s AlphaGo Zero or Carnegie Mellon’s poker playing AI—are perhaps the most headline-grabbing of the bunch. But pattern recognition was the thing that kicked deep learning into overdrive early on, when machine learning algorithms went from struggling to tell dogs and cats apart to outperforming their peers and then their makers in quick succession.
[Watch this video for an AI update from Neil Jacobstein, chair of Artificial Intelligence and Robotics at Singularity University.]
In medicine, deep learning algorithms trained on databases of medical images can spot life-threatening disease with equal or greater accuracy than human professionals. There’s even speculation that AI, if we learn to trust it, could be invaluable in diagnosing disease. And, as Zhavoronkov noted, with more applications and a longer track record that trust is coming.
“Tesla is already putting cars on the street,” Zhavoronkov said. “Three-year, four-year-old technology is already carrying passengers from point A to point B, at 100 miles an hour, and one mistake and you’re dead. But people are trusting their lives to this technology.”
“So, why don’t we do it in pharma?”
Trial and Error and Try Again
AI wouldn’t drive the car in pharmaceutical research. It’d be an assistant that, when paired with a chemist or two, could fast-track discovery by screening more possibilities for better candidates.
There’s plenty of room to make things more efficient, according to Zhavoronkov.
Drug discovery is arduous and expensive. Chemists sift tens of thousands of candidate compounds for the most promising to synthesize. Of these, a handful will go on to further research, fewer will make it to human clinical trials, and a fraction of those will be approved.
The whole process can take many years and cost hundreds of millions of dollars.
This is a big data problem if ever there was one, and deep learning thrives on big data. Early applications have shown their worth unearthing subtle patterns in huge training databases. Although drug-makers already use software to sift compounds, such software requires explicit rules written by chemists. AI’s allure is its ability to learn and improve on its own.
“There are two strategies for AI-driven innovation in pharma to ensure you get better molecules and much faster approvals,” Zhavoronkov said. “One is looking for the needle in the haystack, and another one is creating a new needle.”
To find the needle in the haystack, algorithms are trained on large databases of molecules. Then they go looking for molecules with attractive properties. But creating a new needle? That’s a possibility enabled by the generative adversarial networks Zhavoronkov specializes in.
Such algorithms pit two neural networks against each other. One generates meaningful output while the other judges whether this output is true or false, Zhavoronkov said. Together, the networks generate new objects like text, images, or in this case, molecular structures.
“We started employing this particular technology to make deep neural networks imagine new molecules, to make it perfect right from the start. So, to come up with really perfect needles,” Zhavoronkov said. “[You] can essentially go to this [generative adversarial network] and ask it to create molecules that inhibit protein X at concentration Y, with the highest viability, specific characteristics, and minimal side effects.”
Zhavoronkov believes AI can find or fabricate more needles from the array of molecular possibilities, freeing human chemists to focus on synthesizing only the most promising. If it works, he hopes we can increase hits, minimize misses, and generally speed the process up.
Proof’s in the Pudding
Insilico isn’t alone on its drug-discovery quest, nor is it a brand new area of interest.
Last year, a Harvard group published a paper on an AI that similarly suggests drug candidates. The software trained on 250,000 drug-like molecules and used its experience to generate new molecules that blended existing drugs and made suggestions based on desired properties.
An MIT Technology Review article on the subject highlighted a few of the challenges such systems may still face. The results returned aren’t always meaningful or easy to synthesize in the lab, and the quality of these results, as always, is only as good as the data dined upon.
Stanford chemistry professor and Andreesen Horowitz partner, Vijay Pande, said that images, speech, and text—three of the areas deep learning’s made quick strides in—have better, cleaner data. Chemical data, on the other hand, is still being optimized for deep learning. Also, while there are public databases, much data still lives behind closed doors at private companies.
To overcome the challenges and prove their worth, Zhavoronkov said, his company is very focused on validating the tech. But this year, skepticism in the pharmaceutical industry seems to be easing into interest and investment.
AI drug discovery startup Exscientia inked a deal with Sanofi for $280 million and GlaxoSmithKline for $42 million. Insilico is also partnering with GlaxoSmithKline, and Numerate is working with Takeda Pharmaceutical. Even Google may jump in. According to an article in Nature outlining the field, the firm’s deep learning project, Google Brain, is growing its biosciences team, and industry watchers wouldn’t be surprised to see them target drug discovery.
With AI and the hardware running it advancing rapidly, the greatest potential may yet be ahead. Perhaps, one day, all 1060 molecules in drug-space will be at our disposal. “You should take all the data you have, build n new models, and search as much of that 1060 as possible” before every decision you make, Brandon Allgood, CTO at Numerate, told Nature.
Today’s projects need to live up to their promises, of course, but Zhavoronkov believes AI will have a big impact in the coming years, and now’s the time to integrate it. “If you are working for a pharma company, and you’re still thinking, ‘Okay, where is the proof?’ Once there is a proof, and once you can see it to believe it—it’s going to be too late,” he said.
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