Your Digital Avatar May One Day Get Sick Before You Do
Artificial intelligence is everywhere, just not in the way you think it is.
These networks, loosely designed after the human brain, are interconnected computers that have the ability to "learn."
"There's the perception of AI in the glossy magazines," says Anders Kofod-Petersen, a professor of Artificial Intelligence at the Norwegian University of Science and Technology. "That's the sci-fi version. It resembles the small guy in the movie AI. It might be benevolent or it might be evil, but it's generally intelligent and conscious."
"And this is, of course, as far from the truth as you can possibly get."
What Exactly Is Artificial Intelligence, Anyway?
Let's start with how you got to this piece. You likely came to it through social media. Your Facebook account, Twitter feed, or perhaps a Google search. AI influences all of those things, machine learning helping to run the algorithms that decide what you see, when, and where. AI isn't the little humanoid figure; it's the system that controls the figure.
"AI is being confused with robotics," Eleonore Pauwels, Director of the Anticipatory Intelligence Lab with the Science and Technology Innovation Program at the Wilson Center, says. "What AI is right now is a data optimization system, a very powerful data optimization system."
The revolution in recent years hasn't come from the method scientists and other researchers use. The general ideas and philosophies have been around since the late 1960s. Instead, the big change has been the dramatic increase in computing power, primarily due to the development of neural networks. These networks, loosely designed after the human brain, are interconnected computers that have the ability to "learn." An AI, for example, can be taught to spot a picture of a cat by looking at hundreds of thousands of pictures that have been labeled "cat" and "learning" what a cat looks like. Or an AI can beat a human at Go, an achievement that just five years ago Kofod-Petersen thought wouldn't be accomplished for decades.
"It's very difficult to argue that something is intelligent if it can't learn, and these algorithms are getting pretty good at learning stuff. What they are not good at is learning how to learn."
Medicine is the field where this expertise in perception tasks might have the most influence. It's already having an impact as iPhones use AI to detect cancer, Apple watches alert the wearer to a heart problem, AI spots tuberculosis and the spread of breast cancer with a higher accuracy than human doctors, and more. Every few months, another study demonstrates more possibility. (The New Yorker published an article about medicine and AI last year, so you know it's a serious topic.)
But this is only the beginning. "I personally think genomics and precision medicine is where AI is going to be the biggest game-changer," Pauwels says. "It's going to completely change how we think about health, our genomes, and how we think about our relationship between our genotype and phenotype."
The Fundamental Breakthrough That Must Be Solved
To get there, however, researchers will need to make another breakthrough, and there's debate about how long that will take. Kofod-Petersen explains: "If we want to move from this narrow intelligence to this broader intelligence, that's a very difficult problem. It basically boils down to that we haven't got a clue about what intelligence actually is. We don't know what intelligence means in a biological sense. We think we might recognize it but we're not completely sure. There isn't a working definition. We kind of agree with the biologists that learning is an aspect of it. It's very difficult to argue that something is intelligent if it can't learn, and these algorithms are getting pretty good at learning stuff. What they are not good at is learning how to learn. They can learn specific tasks but we haven't approached how to teach them to learn to learn."
In other words, current AI is very, very good at identifying that a picture of a cat is, in fact, a cat – and getting better at doing so at an incredibly rapid pace – but the system only knows what a "cat" is because that's what a programmer told it a furry thing with whiskers and two pointy ears is called. If the programmer instead decided to label the training images as "dogs," the AI wouldn't say "no, that's a cat." Instead, it would simply call a furry thing with whiskers and two pointy ears a dog. AI systems lack the explicit inference that humans do effortlessly, almost without thinking.
Pauwels believes that the next step is for AI to transition from supervised to unsupervised learning. The latter means that the AI isn't answering questions that a programmer asks it ("Is this a cat?"). Instead, it's almost like it's looking at the data it has, coming up with its own questions and hypothesis, and answering them or putting them to the test. Combining this ability with the frankly insane processing power of the computer system could result in game-changing discoveries.
In the not-too-distant future, a doctor could run diagnostics on a digital avatar, watching which medical conditions present themselves before the person gets sick in real life.
One company in China plans to develop a way to create a digital avatar of an individual person, then simulate that person's health and medical information into the future. In the not-too-distant future, a doctor could run diagnostics on a digital avatar, watching which medical conditions presented themselves – cancer or a heart condition or anything, really – and help the real-life version prevent those conditions from beginning or treating them before they became a life-threatening issue.
That, obviously, would be an incredibly powerful technology, and it's just one of the many possibilities that unsupervised AI presents. It's also terrifying in the potential for misuse. Even the term "unsupervised AI" brings to mind a dystopian landscape where AI takes over and enslaves humanity. (Pick your favorite movie. There are dozens.) This is a concern, something for developers, programmers, and scientists to consider as they build the systems of the future.
The Ethical Problem That Deserves More Attention
But the more immediate concern about AI is much more mundane. We think of AI as an unbiased system. That's incorrect. Algorithms, after all, are designed by someone or a team, and those people have explicit or implicit biases. Intentionally, or more likely not, they introduce these biases into the very code that forms the basis for the AI. Current systems have a bias against people of color. Facebook tried to rectify the situation and failed. These are two small examples of a larger, potentially systemic problem.
It's vital and necessary for the people developing AI today to be aware of these issues. And, yes, avoid sending us to the brink of a James Cameron movie. But AI is too powerful a tool to ignore. Today, it's identifying cats and on the verge of detecting cancer. In not too many tomorrows, it will be on the forefront of medical innovation. If we are careful, aware, and smart, it will help simulate results, create designer drugs, and revolutionize individualize medicine. "AI is the only way to get there," Pauwels says.
Schizophrenia is a debilitating mental health condition that affects around 24 million people worldwide. Patients experience hallucinations and delusions when they develop schizophrenia, with experts referring to these new thoughts and behaviors as positive symptoms. They also suffer from negative symptoms in which they lose important functions, suffering from dulled emotions, lack of purpose and social withdrawal.
Currently available drugs can control only a portion of these symptoms but, on August 8th, Karuna Therapeutics announced its completion of a phase 3 clinical trial that found a new drug called KarXT could treat both positive and negative symptoms of schizophrenia. It could mean substantial progress against a problem that has stymied scientists for decades.
A long-standing problem
Since the 1950s, antipsychotics have been used to treat schizophrenia. People who suffer from it are thought to have too much of a brain chemical called dopamine, and antipsychotics work by blocking dopamine receptors in the brain. They can be effective in treating positive symptoms but have little impact on the negative ones, which can be devastating for a patient’s quality of life, making it difficult to maintain employment and have successful relationships. About 30 percent of schizophrenia patients don't actually respond to antipsychotics at all. Current drugs can also have adverse side effects including elevated cholesterol, high blood pressure, diabetes and movements that patients cannot control.
The recent clinical trial heralds a new treatment approach. “We believe it marks an important advancement for patients given its new and completely different mechanism of action from current therapies,” says Andrew Miller, COO of Karuna.
Scientists have been looking to develop alternatives. However, “the field of drug treatment of schizophrenia is currently in the doldrums,” says Peter McKenna, a senior researcher at FIDMAG Research Foundation in Spain which specialises in mental health.
In the 2000s there was a major push to target a brain receptor for a chemical called glutamate. Evidence suggested that this receptor is abnormal in the brains of schizophrenia patients, but attempts to try glutamate failed in clinical trials.
After that, many pharmaceutical companies dropped out of the race for a more useful treatment. But some companies continued to search, such as Karuna Therapeutics, led by founder and Chief Operating Officer Andrew Miller and CEO Steve Paul. The recent clinical trial suggests their persistence has led to an important breakthrough with their drug, KarXT. “We believe it marks an important advancement for patients given its new and completely different mechanism of action from current therapies,” Miller says.
How it works
Neurotransmitters are chemical messengers that pass signals between neurons. To work effectively, neurotransmitters need a receptor to bind to. A neurotransmitter called acetylcholine seems to be especially important in schizophrenia. It interacts with sites called muscarinic receptors, which are involved in the network of nerves that calm your body after a stressful event. Post mortem studies in people with schizophrenia have shown that two muscarinic receptors in the brain, the M1 and M4 receptors, are activated at unusually low levels because they don’t receive enough signals from acetylcholine.
The M4 receptor appears to play a role in psychosis. The M1 receptor is also associated with psychosis but is primarily thought to be involved in cognition. KarXT, taken orally, works by activating both of these receptors to signal properly. It is this twofold action that seems to explain its effectiveness. “[The drug’s] design enables the preferential stimulation of these muscarinic receptors in the brain,” Miller says.
How it developed
It all started in the early 1990s when Paul was at pharmaceutical company Eli Lilly. He discovered that Xanomeline, the drug they were testing on Alzheimer's patients, had antipsychotic effects. It worked by stimulating M1 and M4 receptors, so he and his colleagues decided to test Xanomeline on schizophrenia patients, supported by research on the connection between muscarinic receptors and psychosis. They found that Xanomeline reduced both positive and negative symptoms.
Unfortunately, it also caused significant side effects. The problem was that stimulating the M1 and M4 receptors in the brain also stimulated muscarinic receptors in the body that led to severe vomiting, diarrhea and even the temporary loss of consciousness.
In the end, Eli Lilly discontinued the clinical trials for the drug, but Miller set up Karuna Therapeutics to develop a solution. “I was determined to find a way to harness the therapeutic benefit demonstrated in studies of Xanomeline, while eliminating side effects that limited its development,” Miller says.
He analysed over 7,000 possible ways of mixing Xanomeline with other agents before settling on KarXT. It combines Xanomeline with a drug called Trospium Chloride, which blocks muscarinic receptors in the body – taking care of the side effects such as vomiting – but leaves them unblocked in the brain. Paul was so excited by Miller’s progress that he joined Karuna after leaving Eli Lilly and founding two previous startups.
“It's a very important approach,” says Rick Adams, Future Leaders Fellow in the Institute of Cognitive Neuroscience and Centre for Medical Image Computing at University College London. “We are in desperate need of alternative drug targets and this target is one of the best. There are other alternative targets, but not many are as close to being successful as the muscarinic receptor drug.”
Clinical Trial
Following a successful phase 2 clinical trial in 2019, the most recent trial involved 126 patients who were given KarXT, and 126 who were given a placebo. Compared to the placebo, patients taking KarXT had a significant 9.6 point reduction in the positive and negative syndrome scale (PANSS), the standard for rating schizophrenic symptoms.
KarXT also led to statistically significant declines in positive and negative symptoms compared to the placebo. “The results suggest that KarXT could be a potentially game-changing option in the management of both positive and negative symptoms of schizophrenia,” Miller says.
Robert McCutcheon, a psychiatrist and neuroscientist at Oxford University, is optimistic about the side effects but highlights the need for more safety trials.
McKenna, the researcher at FIDMAG Foundation, agrees about the drug’s potential. “The new [phase 3] study is positive,” he says. “It is reassuring that one is not dealing with a drug that works in one trial and then inexplicably fails in the next one.”
Robert McCutcheon, a psychiatrist and neuroscientist at Oxford University, said the drug is an unprecedented step forward. “KarXT is one of the first drugs with a novel mechanism of action to show promise in clinical trials.”
Even though the drug blocks muscarine receptors in the body, some patients still suffered from adverse side effects like vomiting, dizziness and diarrhea. But in general, these effects were mild to moderate, especially compared to dopamine-blocking antipsychotics or Xanomeline on its own.
McCutcheon is optimistic about the side effects but highlights the need for more safety trials. “The trial results suggest that gastrointestinal side effects appear to be manageable,” he says. “We know, however, from previous antipsychotic drugs that the full picture regarding the extent of side effects can sometimes take longer to become apparent to clinicians and patients. Careful ongoing assessment during a longer period of treatment will therefore be important.”
The Future
The team is currently conducting three other trials to evaluate the efficacy and long-term safety of KarXT. Their goal is to receive FDA approval next year.
Karuna is also conducting trials to evaluate the effectiveness of KarXT in treating psychosis in patients suffering from Alzheimer’s.
The big hope is that they will soon be able to provide a radically different drug to help many patients with schizophrenia. “We are another step closer to potentially providing the first new class of medicine in more than 50 years to the millions of people worldwide living with schizophrenia,” says Miller.
Podcast: The Friday Five weekly roundup in health research
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- Using graphene to repair shoulders
- Testing for PTSD with saliva
- Cancer detection with a microchip
- Best posture for pill taking
- Resilient food for climate change
And an honorable mention goes to research on a new way to induce healthy fat.