The Promise of Pills That Know When You Swallow Them
Dr. Sara Browne, an associate professor of clinical medicine at the University of California, San Diego, is a specialist in infectious diseases and, less formally, "a global health person." She often travels to southern Africa to meet with colleagues working on the twin epidemics of HIV and tuberculosis.
"This technology, in my opinion, is an absolute slam dunk for tuberculosis."
Lately she has asked them to name the most pressing things she can help with as a researcher based in a wealthier country. "Over and over and over again," she says, "the only thing they wanted to know is whether their patients are taking the drugs."
Tuberculosis is one of world's deadliest diseases; every year there are 10 million new infections and more than a million deaths. When a patient with tuberculosis is prescribed medicine to combat the disease, adherence to the regimen is important not just for the individual's health, but also for the health of the community. Poor adherence can lead to lengthier and more costly treatment and, perhaps more importantly, to drug-resistant strains of the disease -- an increasing global threat.
Browne is testing a new method to help healthcare workers track their patients' adherence with greater precision—close to exact precision even. They're called digital pills, and they involve a patient swallowing medicine as they normally would, only the capsule contains a sensor that—when it contacts stomach acid—transmits a signal to a small device worn on or near the body. That device in turn sends a signal to the patient's phone or tablet and into a cloud-based database. The fact that the pill has been swallowed has therefore been recorded almost in real time, and notice is available to whoever has access to the database.
"This technology, in my opinion, is an absolute slam dunk for tuberculosis," Browne says. TB is much more prevalent in poorer regions of the world—in Sub-Saharan Africa, for example—than in richer places like the U.S., where Browne's studies thus far have taken place. But when someone is diagnosed in the U.S., because of the risk to others if it spreads, they will likely have to deal with "directly observed therapy" to ensure that they take their medicines correctly.
DOT, as it's called, requires the patient to meet with a healthcare worker several days a week, or every day, so that the medicine intake can be observed in person -- an expensive and time-consuming process. Still, the Centers for Disease Control and Prevention website says (emphasis theirs), "DOT should be used for ALL patients with TB disease, including children and adolescents. There is no way to accurately predict whether a patient will adhere to treatment without this assistance."
Digital pills can help with both the cost and time involved, and potentially improve adherence in places where DOT is impossibly expensive. With the sensors, you can monitor a patient's adherence without a healthcare worker physically being in the room. Patients can live their normal lives and if they miss a pill, they can receive a reminder by text or a phone call from the clinic or hospital. "They can get on with their lives," said Browne. "They don't need the healthcare system to interrupt them."
A 56-year-old patient who participated in one of Browne's studies when he was undergoing TB treatment says that before he started taking the digital pills, he would go to the clinic at least once every day, except weekends. Once he switched to digital pills, he could go to work and spend time with his wife and children instead of fighting traffic every day to get to the clinic. He just had to wear a small patch on his abdomen, which would send the signal to a tablet provided by Browne's team. When he returned from work, he could see the results—that he'd taken the pill—in a database accessed via the tablet. (He could also see his heart rate and respiratory rate.) "I could do my daily activities without interference," he said.
Dr. Peter Chai, a medical toxicologist and emergency medicine physician at Brigham and Women's Hospital in Boston, is studying digital pills in a slightly different context, to help fight the country's opioid overdose crisis. Doctors like Chai prescribe pain medicine, he says, but then immediately put the onus on the patient to decide when to take it. This lack of guidance can lead to abuse and addiction. Patients are often told to take the meds "as needed." Chai and his colleagues wondered, "What does that mean to patients? And are people taking more than they actually need? Because pain is such a subjective experience."
The patients "liked the fact that somebody was watching them."
They wanted to see what "take as needed" actually led to, so they designed a study with patients who had broken a bone and come to the hospital's emergency department to get it fixed. Those who were prescribed oxycodone—a pharmaceutical opioid for pain relief—got enough digital pills to last one week. They were supposed to take the pills as needed, or as many as three pills per day. When the pills were ingested, the sensor sent a signal to a card worn on a lanyard around the neck.
Chai and his colleagues were able to see exactly when the patients took the pills and how many, and to detect patterns of ingestion more precisely than ever before. They talked to the patients after the seven days were up, and Chai said most were happy to be taking digital pills. The patients saw it as a layer of protection from afar. "They liked the fact that somebody was watching them," Chai said.
Both doctors, Browne and Chai, are in early stages of studies with patients taking pre-exposure prophylaxis, medicines that can protect people with a high-risk of contracting HIV, such as injectable drug users. Without good adherence, patients leave themselves open to getting the virus. If a patient is supposed to take a pill at 2 p.m. but the digital pill sensor isn't triggered, the healthcare provider can have an automatic message sent as a reminder. Or a reminder to one of the patient's friends or loved ones.
"Like Swallowing Your Phone"?
Deven Desai, an associate professor of law and ethics at Georgia Tech, says that digital pills sound like a great idea for helping with patient adherence, a big issue that self-reporting doesn't fully solve. He likes the idea of a physician you trust having better information about whether you're taking your medication on time. "On the surface that's just cool," he says. "That's a good thing." But Desai, who formerly worked as academic research counsel at Google, said that some of the same questions that have come up in recent years with social media and the Internet in general also apply to digital pills.
"Think of it like your phone, but you swallowed it," he says. "At first it could be great, simple, very much about the user—in this case, the patient—and the data is going between you and your doctor and the medical people it ought to be going to. Wonderful. But over time, phones change. They become 'smarter.'" And when phones and other technologies become smarter, he says, the companies behind them tend to expand the type of data they collect, because they can. Desai says it will be crucial that prescribers be completely transparent about who is getting the patients' data and for what purpose.
"We're putting stuff in our body in good faith with our medical providers, and what if it turned out later that all of a sudden someone was data mining or putting in location trackers and we never knew about that?" Desai asks. "What science has to realize is if they don't start thinking about this, what could be a wonderful technology will get killed."
Leigh Turner, an associate professor at the University of Minnesota's Center for Bioethics, agrees with Desai that digital pills have great promise, and also that there are clear reasons to be concerned about their use. Turner compared the pills to credit cards and social media, in that the data from them can potentially be stolen or leaked. One question he would want answered before the pills were normalized: "What kind of protective measures are in place to make sure that personal information isn't spilling out and being acquired by others or used by others in unexpected and unwanted ways?"
If digital pills catch on, some experts worry that they may one day not be a voluntary technology.
Turner also wonders who will have access to the pills themselves. Only those who can afford both the medicine plus the smartphones that are currently required for their use? Or will people from all economic classes have access? If digital pills catch on, he also worries they may one day not be a voluntary technology.
"When it comes to digital pills, it's not something that's really being foisted on individuals. It's more something that people can be informed of and can choose to take or not to take," he says. "But down the road, I can imagine a scenario where we move away from purely voluntary agreements to it becoming more of an expectation."
He says it's easy to picture a scenario in which insurance companies demand that patient medicinal intake data be tracked and collected or else. Refuse to have your adherence tracked and you risk higher rates or even overall coverage. Maybe patients who don't take the digital pills suffer dire consequences financially or medically. "Maybe it becomes beneficial as much to health insurers and payers as it is to individual patients," Turner says.
In November 2017, the FDA approved the first-ever digital pill that includes a sensor, a drug called Abilify MyCite, made by Otsuka Pharmaceutical Company. The drug, which is yet to be released, is used to treat schizophrenia, bipolar disorder, and depression. With a built-in sensor developed by Proteus Digital Health, patients can give their doctors permission to see when exactly they are taking, or not taking, their meds. For patients with mental illness, the ability to help them stick to their prescribed regime can be life-saving.
But Turner wonders if Abilify is the best drug to be a forerunner for digital pills. Some people with schizophrenia might be suffering from paranoia, and perhaps giving them a pill developed by a large corporation that sends data from their body to be tracked by other people might not be the best idea. It could in fact exacerbate their sense of paranoia.
The Bottom Line: Protect the Data
We all have relatives who have pillboxes with separate compartments for each day of the week, or who carry pillboxes that beep when it's time to take the meds. But that's not always good enough for people with dementia, mental illness, drug addiction, or other life situations that make it difficult to remember to take their pills. Digital pills can play an important role in helping these people.
"The absolute principle here is that the data has to belong to the patient."
The one time the patient from Browne's study forgot to take his pills, he got a beeping reminder from his tablet that he'd missed a dose. "Taking a medication on a daily basis, sometimes we just forget, right?" he admits. "With our very accelerated lives nowadays, it helps us to remember that we have to take the medications. So patients are able to be on top of their own treatment."
Browne is convinced that digital pills can help people in developing countries with high rates of TB and HIV, though like Turner and Desai she cautions that patients' data must be protected. "I think it can be a tremendous technology for patient empowerment and I also think if properly used it can help the medical system to support patients that need it," she said. "But the absolute principle here is that the data has to belong to the patient."
CandyCodes could provide sweet justice against fake pills
When we swallow a pill, we hope it will work without side effects. Few of us know to worry about a growing issue facing the pharmaceutical industry: counterfeit medications. These pills, patches, and other medical products might look just like the real thing. But they’re often stuffed with fillers that dilute the medication’s potency or they’re simply substituted for lookalikes that contain none of the prescribed medication at all.
Now, bioengineer William Grover at the University of California, Riverside, may have a solution. Inspired by the tiny, multi-colored sprinkles called nonpareils that decorate baked goods and candies, Grover created CandyCodes pill coatings to prevent counterfeits.
The idea was borne out of pandemic boredom. Confined to his home, Grover was struck by the patterns of nonpareils he saw on candies, and found himself counting the number of little balls on each one. “It’s random, how they’re applied,” he says. “I wondered if it ever repeats itself or if each of these candies is unique in the entire world.” He suspected the latter, and some quick math proved his hypothesis: Given dozens of nonpareils per candy in a handful of different colors, it’s highly unlikely that the sprinklings on any two candies would be identical.
He quickly realized his finding could have practical applications: pills or capsules could be coated with similar “sprinkles,” with the manufacturer photographing each pill or capsule before selling its products. Consumers looking to weed out fakes could potentially take a photo with their cell phones and go online to compare images of their own pills to the manufacturer’s database, with the help of an algorithm that would determine their authenticity. Or, a computer could generate another type of unique identifier, such as a text-based code, tracking to the color and location of the sprinkles. This would allow for a speedier validation than a photo-based comparison, Grover says. “It could be done very quickly, in a fraction of a second.”
Researchers and manufacturers have already developed some anti-counterfeit tools, including built-in identifiers like edible papers with scannable QR codes. But such methods, while functional, can be costly to implement, Grover says.
It wouldn’t be paranoid to take such precautions. Counterfeits are a growing problem, according to Young Kim, a biomedical engineer at Purdue University who was not involved in the CandyCodes study. “There are approximately 40,000 online pharmacies that one can access via the Internet,” he says. “Only three to four percent of them are operated legally.” Purchases from online pharmacies rose dramatically during the pandemic, and Kim expects a boom in counterfeit medical products alongside it.
The FDA warns that U.S. consumers can be exposed to counterfeits through online purchases, in particular. The problem is magnified in low- to middle-income nations, where one in 10 medical products are counterfeit, according to a World Health Organization estimate. Cost doesn’t seem to be a factor, either; antimalarials and antibiotics are most often reported as counterfeits or fakes, and generic medications are swapped as often as brand-name drugs, according to the same WHO report.
Counterfeits weren’t tracked globally until 2013; since then, there have been 1,500 reports to the WHO, with actual incidences of counterfeiting likely much higher. Fake medicines have been estimated to result in costs of $200 billion each year, and are blamed for more than 72,000 pneumonia- and 116,000 malaria-related deaths.
Researchers and manufacturers have already developed some anti-counterfeit tools, including built-in identifiers like edible papers with scannable QR codes or barcodes that are stamped onto or otherwise incorporated into pills and other medical products. But such methods, while functional, can be costly to implement, Grover says.
CandyCodes could provide unique identifiers for at least 41 million pills for every person on the planet.
William Grover
“Putting universal codes on each pill and each dosage is attractive,” he says. “The challenge is, how can we do it in a way that requires as little modification to the existing manufacturing process as possible? That's where I hope CandyCodes have an edge. It's not zero modification, but I hope it is as minor a modification of the manufacturing process as possible.”
Kim calls the concept “a clever idea to introduce entropy for high-level security” even if it may not be as close to market as other emerging technologies, including some edible watermarks he’s helped develop. He points out that CandyCodes still needs to be tested for reproducibility and readability.
The possibilities are already intriguing, though. Grover’s recent research, published in Scientific Reports, predicts that unique codes could be used for at least 41 million pills for every person on the planet.
Sadly, CandyCodes’ multicolored bits probably won’t taste like candy. They must be made of non-caloric ingredients to meet the international regulatory standards that govern food dyes and colorants. But Grover hopes CandyCodes represent a simple, accessible solution to a heart-wrenching issue. “This feels like trying to track down and go after bad guys,” he says. “Someone who would pass off a medicine intended for a child or a sick person and pass it off as something effective, I can't imagine anything much more evil than that. It's fun and, and a little fulfilling to try to develop technologies that chip away at that.”
Waste smothering our oceans is worth billions – here’s what we can do with all that sh$t
There’s hardly a person out there who hasn’t heard of the Great Pacific Garbage Patch. That type of pollution is impossible to miss. It stares you in the face from pictures and videos of sea turtles with drinking straws up their noses and acres of plastic swirling in the sea.
It demands you to solve the problem—and it works. The campaign to raise awareness about plastic pollution in the oceans has resulted in new policies, including bans on microplastics in personal care products, technology to clean up the plastic, and even new plastic-like materials that are better for the environment.
But there’s a different type of pollution smothering the ocean as you read this. Unfortunately, this one is almost invisible, but no less damaging. In fact, it’s even more serious than plastic and most people have no idea it even exists. It is literally under our noses, destroying our oceans, lakes, and rivers – and yet we are missing it completely while contributing to it daily. In fact, we exacerbate it multiple times a day—every time we use the bathroom.
It is the way we do our sewage.
Most of us don’t think much about what happens after we flush the toilet. Most of us probably assume that the substances we flush go “somewhere” and are dealt with safely. But we typically don’t think about it beyond that.
Most of us also probably don’t think about what’s in the ocean or lakes we swim in. Since others are swimming, jumping in is just fine. But our waterways are far from clean. In fact, at times they are incredibly filthy. In the US, we are dumping 1.2 trillion of gallons of untreated sewage into the environment every year. Just New York City alone discharges 27 billion gallons into the Hudson River basin annually.
How does this happen? Part of it is the unfortunate side effect of our sewage system design that dates back to over a century ago when cities were smaller and fewer people were living so close together.
Back then, engineers designed the so-called “combine sewer overflow systems,” or CSOs, in which the storm water pipes are connected to the sanitary sewer pipes. In normal conditions, the sewage effluent from homes flows to the treatment plants where it gets cleaned and released into the waterways. But when it rains, the pipe system becomes so overwhelmed with water that the treatment plant can’t process it fast enough. So the treatment plant has to release the excess water through its discharge pipes—directly, without treatment, into streams, rivers and the ocean.
The 1.2 trillion gallons of CSO releases isn’t even the full picture. There are also discharges from poorly maintained septic systems, cesspools and busted pipes of the aging wastewater infrastructure. The state of Hawaii alone has 88,000 cesspools that need replacing and are currently leaking 53 million gallons of raw sewage daily into their coastal waters. You may think twice about swimming on your Hawaii vacations.
Overall, the US is facing a $271 billion backlog in wastewater infrastructure projects to update these aging systems. Across the Western world, countries are facing similar challenges with their aging sewage systems, especially the UK and European Union.
That’s not to say that other parts of the planet are in better shape. Out of the 7+ billion people populating our earth, 4.2 billion don’t have access to safe sanitation. Included in this insane number are roughly 2 billion people who have no toilet at all. Whether washed by rains or dumped directly into the waterways, a lot of this sludge pollutes the environment, the drinking water, and ultimately the ocean.
Pipes pour water onto a rocky shore in Jakarta, Indonesia.
Tom Fisk
What complicates this from an ocean health perspective is that it’s not just poop and pee that gets dumped into nearby waterways. It is all the things we put in and on our bodies and flush down our drains. That vicious mix of chemicals includes caffeine, antibiotics, antidepressants, painkillers, hormones, microplastics, cocaine, cooking oils, paint thinners, and PFAS—the forever chemicals present in everything from breathable clothing to fire retardant fabrics of our living room couches. Recent reports have found all of the above substances in fish—and then some.
Why do we allow so much untreated sewage spill into the sea? Frankly speaking, for decades scientists and engineers thought that the ocean could handle it. The mantra back then was “dilution is the solution to pollution,” which might’ve worked when there were much fewer people living on earth—but not now. Today science is telling us that this old approach doesn’t hold. That marine habitats are much more sensitive than we had expected and can’t handle the amount of wastewater we are discharging into them.
The excess nitrogen and phosphorus that the sewage (and agricultural runoff) dumps into the water causes harmful algal blooms, more commonly known as red or brown tides. The water column is overtaken by tiny algae that sucks up all the oxygen from the water, creating dead zones like the big fish kills in the Gulf of Mexico. These algae also cause public health issues by releasing gases toxic to people and animals, including dementia, neurological damage, and respiratory illness. Marshes and mangroves end up with weakened root systems and start dying off. In a wastewater modeling study I published last year, we found that 31 percent of salt marshes globally were heavily polluted with human sewage. Coral reefs get riddled with disease and overgrown by seaweed.
We could convert sewage into high-value goods. It can be used to generate electricity, fertilizer, and drinking water. The technologies not only exist but are getting better and more efficient all the time.
Moreover, by way of our sewage, we managed to transmit a human pathogen—Serratia marcescens, which causes urinary, respiratory and other infections in people—to corals! Recent reports from the Florida Keys are showing white pox disease popping up in elk horn corals caused by S.marcescens, which somehow managed to jump species. Many recent studies have documented just how common this type of pollution is across the globe.
Yet, there is some good news in that abysmal sewage flow. Just like with plastic pollution, realizing that there’s a problem is the first step, so awareness is key. That’s exactly why I co-founded Ocean Sewage Alliance last year—a nonprofit that aims to “re-potty train the world” by breaking taboos in talking about the poop and pee problem, as well as uniting experts from various key sectors to work together to end sewage pollution in coastal areas.
To end this pollution, we have to change the ways we handle our sewage. Even more exciting is that by solving the sewage problem we can create all sorts of economic benefits. In 2015, human poop was valued at $9.5 billion a year globally, which today would be $11.5 billion per year.
What would one do with that sh$t?
We could convert it into high-value goods. Sewage can be used to generate electricity, fertilizer, and drinking water. The technologies not only exist but are getting better and more efficient all the time. Some exciting examples include biodigesters and urine diversion (or peecycling) systems that can produce fertilizer and biogas, essentially natural gas. The United Nations estimates that the biogas produced from poop could provide electricity for 138 million homes. And the recovered and cleaned water can be used for irrigation, laundry and flushing toilets. It can even be refined to the point that it is safe for drinking water – just ask the folks in Orange County, CA who have been doing so for the last few decades.
How do we deal with all the human-made pollutants in our sewage? There is technology for that too. Called pyrolysis, it heats up sludge to high temperatures in the absence of oxygen, which causes most of the substances to degrade and fall apart.
There are solutions to the problems—as long as we acknowledge that the problems exist. The fact that you are reading this means that you are part of the solution already. The next time you flush your toilet, think about where this output may flow. Does your septic system work properly? Does your local treatment plant discharge raw sewage on rainy days? Can that plant implement newer technologies that can upcycle waste? These questions are part of re-potty training the world, one household at a time. And together, these households are the force that can turn back the toxic sewage tide. And keep our oceans blue.