The Algorithm Will See You Now
There's a quiet revolution going on in medicine. It's driven by artificial intelligence, but paradoxically, new technology may put a more human face on healthcare.
AI's usefulness in healthcare ranges far and wide.
Artificial intelligence is software that can process massive amounts of information and learn over time, arriving at decisions with striking accuracy and efficiency. It offers greater accuracy in diagnosis, exponentially faster genome sequencing, the mining of medical literature and patient records at breathtaking speed, a dramatic reduction in administrative bureaucracy, personalized medicine, and even the democratization of healthcare.
The algorithms that bring these advantages won't replace doctors; rather, by offloading some of the most time-consuming tasks in healthcare, providers will be able to focus on personal interactions with patients—listening, empathizing, educating and generally putting the care back in healthcare. The relationship can focus on the alleviation of suffering, both the physical and emotional kind.
Challenges of Getting AI Up and Running
The AI revolution, still in its early phase in medicine, is already spurring some amazing advances, despite the fact that some experts say it has been overhyped. IBM's Watson Health program is a case in point. IBM capitalized on Watson's ability to process natural language by designing algorithms that devour data like medical articles and analyze images like MRIs and medical slides. The algorithms help diagnose diseases and recommend treatment strategies.
But Technology Review reported that a heavily hyped partnership with the MD Anderson Cancer Center in Houston fell apart in 2017 because of a lack of data in the proper format. The data existed, just not in a way that the voraciously data-hungry AI could use to train itself.
The hiccup certainly hasn't dampened the enthusiasm for medical AI among other tech giants, including Google and Apple, both of which have invested billions in their own healthcare projects. At this point, the main challenge is the need for algorithms to interpret a huge diversity of data mined from medical records. This can include everything from CT scans, MRIs, electrocardiograms, x-rays, and medical slides, to millions of pages of medical literature, physician's notes, and patient histories. It can even include data from implantables and wearables such as the Apple Watch and blood sugar monitors.
None of this information is in anything resembling a standard format across and even within hospitals, clinics, and diagnostic centers. Once the algorithms are trained, however, they can crunch massive amounts of data at blinding speed, with an accuracy that matches and sometimes even exceeds that of highly experienced doctors.
Genome sequencing, for example, took years to accomplish as recently as the early 2000s. The Human Genome Project, the first sequencing of the human genome, was an international effort that took 13 years to complete. In April of this year, Rady Children's Institute for Genomic Medicine in San Diego used an AI-powered genome sequencing algorithm to diagnose rare genetic diseases in infants in about 20 hours, according to ScienceDaily.
"Patient care will always begin and end with the doctor."
Dr. Stephen Kingsmore, the lead author of an article published in Science Translational Medicine, emphasized that even though the algorithm helped guide the treatment strategies of neonatal intensive care physicians, the doctor was still an indispensable link in the chain. "Some people call this artificial intelligence, we call it augmented intelligence," he says. "Patient care will always begin and end with the doctor."
One existing trend is helping to supply a great amount of valuable data to algorithms—the electronic health record. Initially blamed for exacerbating the already crushing workload of many physicians, the EHR is emerging as a boon for algorithms because it consolidates all of a patient's data in one record.
Examples of AI in Action Around the Globe
If you're a parent who has ever taken a child to the doctor with flulike symptoms, you know the anxiety of wondering if the symptoms signal something serious. Kang Zhang, M.D., Ph.D., the founding director of the Institute for Genomic Medicine at the University of California at San Diego, and colleagues developed an AI natural language processing model that used deep learning to analyze the EHRs of 1.3 million pediatric visits to a clinic in Guanzhou, China.
The AI identified common childhood diseases with about the same accuracy as human doctors, and it was even able to split the diagnoses into two categories—common conditions such as flu, and serious, life-threatening conditions like meningitis. Zhang has emphasized that the algorithm didn't replace the human doctor, but it did streamline the diagnostic process and could be used in a triage capacity when emergency room personnel need to prioritize the seriously ill over those suffering from common, less dangerous ailments.
AI's usefulness in healthcare ranges far and wide. In Uganda and several other African nations, AI is bringing modern diagnostics to remote villages that have no access to traditional technologies such as x-rays. The New York Times recently reported that there, doctors are using a pocket-sized, hand-held ultrasound machine that works in concert with a cell phone to image and diagnose everything from pneumonia (a common killer of children) to cancerous tumors.
The beauty of the highly portable, battery-powered device is that ultrasound images can be uploaded on computers so that physicians anywhere in the world can review them and weigh in with their advice. And the images are instantly incorporated into the patient's EHR.
Jonathan Rothberg, the founder of Butterfly Network, the Connecticut company that makes the device, told The New York Times that "Two thirds of the world's population gets no imaging at all. When you put something on a chip, the price goes down and you democratize it." The Butterfly ultrasound machine, which sells for $2,000, promises to be a game-changer in remote areas of Africa, South America, and Asia, as well as at the bedsides of patients in developed countries.
AI algorithms are rapidly emerging in healthcare across the U.S. and the world. China has become a major international player, set to surpass the U.S. this year in AI capital investment, the translation of AI research into marketable products, and even the number of often-cited research papers on AI. So far the U.S. is still the leader, but some experts describe the relationship between the U.S. and China as an AI cold war.
"The future of machine learning isn't sentient killer robots. It's longer human lives."
The U.S. Food and Drug Administration expanded its approval of medical algorithms from two in all of 2017 to about two per month throughout 2018. One of the first fields to be impacted is ophthalmology.
One algorithm, developed by the British AI company DeepMind (owned by Alphabet, the parent company of Google), instantly scans patients' retinas and is able to diagnose diabetic retinopathy without needing an ophthalmologist to interpret the scans. This means diabetics can get the test every year from their family physician without having to see a specialist. The Financial Times reported in March that the technology is now being used in clinics throughout Europe.
In Copenhagen, emergency service dispatchers are using a new voice-processing AI called Corti to analyze the conversations in emergency phone calls. The algorithm analyzes the verbal cues of callers, searches its huge database of medical information, and provides dispatchers with onscreen diagnostic information. Freddy Lippert, the CEO of EMS Copenhagen, notes that the algorithm has already saved lives by expediting accurate diagnoses in high-pressure situations where time is of the essence.
Researchers at the University of Nottingham in the UK have even developed a deep learning algorithm that predicts death more accurately than human clinicians. The algorithm incorporates data from a huge range of factors in a chronically ill population, including how many fruits and vegetables a patient eats on a daily basis. Dr. Stephen Weng, lead author of the study, published in PLOS ONE, said in a press release, "We found machine learning algorithms were significantly more accurate in predicting death than the standard prediction models developed by a human expert."
New digital technologies are allowing patients to participate in their healthcare as never before. A feature of the new Apple Watch is an app that detects cardiac arrhythmias and even produces an electrocardiogram if an abnormality is detected. The technology, approved by the FDA, is helping cardiologists monitor heart patients and design interventions for those who may be at higher risk of a cardiac event like a stroke.
If having an algorithm predict your death sends a shiver down your spine, consider that algorithms may keep you alive longer. In 2018, technology reporter Tristan Greene wrote for Medium that "…despite the unending deluge of panic-ridden articles declaring AI the path to apocalypse, we're now living in a world where algorithms save lives every day. The future of machine learning isn't sentient killer robots. It's longer human lives."
The Risks of AI Compiling Your Data
To be sure, the advent of AI-infused medical technology is not without its risks. One risk is that the use of AI wearables constantly monitoring our vital signs could turn us into a nation of hypochondriacs, racing to our doctors every time there's a blip in some vital sign. Such a development could stress an already overburdened system that suffers from, among other things, a shortage of doctors and nurses. Another risk has to do with the privacy protections on the massive repository of intimately personal information that AI will have on us.
In an article recently published in the Journal of the American Medical Association, Australian researcher Kit Huckvale and colleagues examined the handling of data by 36 smartphone apps that assisted people with either depression or smoking cessation, two areas that could lend themselves to stigmatization if they fell into the wrong hands.
Out of the 36 apps, 33 shared their data with third parties, despite the fact that just 25 of those apps had a privacy policy at all and out of those, only 23 stated that data would be shared with third parties. The recipients of all that data? It went almost exclusively to Facebook and Google, to be used for advertising and marketing purposes. But there's nothing to stop it from ending up in the hands of insurers, background databases, or any other entity.
Even when data isn't voluntarily shared, any digital information can be hacked. EHRs and even wearable devices share the same vulnerability as any other digital record or device. Still, the promise of AI to radically improve efficiency and accuracy in healthcare is hard to ignore.
AI Can Help Restore Humanity to Medicine
Eric Topol, director of the Scripps Research Translational Institute and author of the new book Deep Medicine, says that AI gives doctors and nurses the most precious gift of all: time.
Topol welcomes his patients' use of the Apple Watch cardiac feature and is optimistic about the ways that AI is revolutionizing medicine. He says that the watch helps doctors monitor how well medications are working and has already helped to prevent strokes. But in addition to that, AI will help bring the humanity back to a profession that has become as cold and hard as a stainless steel dissection table.
"When I graduated from medical school in the 1970s," he says, "you had a really intimate relationship with your doctor." Over the decades, he has seen that relationship steadily erode as medical organizations demanded that doctors see more and more patients within ever-shrinking time windows.
"Doctors have no time to think, to communicate. We need to restore the mission in medicine."
In addition to that, EHRs have meant that doctors and nurses are getting buried in paperwork and administrative tasks. This is no doubt one reason why a recent study by the World Health Organization showed that worldwide, about 50 percent of doctors suffer from burnout. People who are utterly exhausted make more mistakes, and medical clinicians are no different from the rest of us. Only medical mistakes have unacceptably high stakes. According to its website, Johns Hopkins University recently announced that in the U.S. alone, 250,000 people die from medical mistakes each year.
"Doctors have no time to think, to communicate," says Topol. "We need to restore the mission in medicine." AI is giving doctors more time to devote to the thing that attracted them to medicine in the first place—connecting deeply with patients.
There is a real danger at this juncture, though, that administrators aware of the time-saving aspects of AI will simply push doctors to see more patients, read more tests, and embrace an even more crushing workload.
"We can't leave it to the administrators to just make things worse," says Topol. "Now is the time for doctors to advocate for a restoration of the human touch. We need to stand up for patients and for the patient-doctor relationship."
AI could indeed be a game changer, he says, but rather than squander the huge benefits of more time, "We need a new equation going forward."
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.