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."
Bacterial antibiotic resistance has been a concern in the medical field for several years. Now a new, similar threat is arising: drug-resistant fungal infections. The Centers for Disease Control and Prevention considers antifungal and antimicrobial resistance to be among the world’s greatest public health challenges.
One particular type of fungal infection caused by Candida auris is escalating rapidly throughout the world. And to make matters worse, C. auris is becoming increasingly resistant to current antifungal medications, which means that if you develop a C. auris infection, the drugs your doctor prescribes may not work. “We’re effectively out of medicines,” says Thomas Walsh, founding director of the Center for Innovative Therapeutics and Diagnostics, a translational research center dedicated to solving the antimicrobial resistance problem. Walsh spoke about the challenges at a Demy-Colton Virtual Salon, one in a series of interactive discussions among life science thought leaders.
Although C. auris typically doesn’t sicken healthy people, it afflicts immunocompromised hospital patients and may cause severe infections that can lead to sepsis, a life-threatening condition in which the overwhelmed immune system begins to attack the body’s own organs. Between 30 and 60 percent of patients who contract a C. auris infection die from it, according to the CDC. People who are undergoing stem cell transplants, have catheters or have taken antifungal or antibiotic medicines are at highest risk. “We’re coming to a perfect storm of increasing resistance rates, increasing numbers of immunosuppressed patients worldwide and a bug that is adapting to higher temperatures as the climate changes,” says Prabhavathi Fernandes, chair of the National BioDefense Science Board.
Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures.
Although medical professionals aren’t concerned at this point about C. auris evolving to affect healthy people, they worry that its presence in hospitals can turn routine surgeries into life-threatening calamities. “It’s coming,” says Fernandes. “It’s just a matter of time.”
An emerging global threat
“Fungi are found in the environment,” explains Fernandes, so Candida spores can easily wind up on people’s skin. In hospitals, they can be transferred from contact with healthcare workers or contaminated surfaces. Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures. It can enter the body during medical treatments that break the skin—and cause an infection. Overall, fungal infections cost some $48 billion in the U.S. each year. And infection rates are increasing because, in an ironic twist, advanced medical therapies are enabling severely ill patients to live longer and, therefore, be exposed to this pathogen.
The first-ever case of a C. auris infection was reported in Japan in 2009, although an analysis of Candida samples dated the earliest strain to a 1996 sample from South Korea. Since then, five separate varieties – called clades, which are similar to strains among bacteria – developed independently in different geographies: South Asia, East Asia, South Africa, South America and, recently, Iran. So far, C. auris infections have been reported in 35 countries.
In the U.S., the first infection was reported in 2016, and the CDC started tracking it nationally two years later. During that time, 5,654 cases have been reported to the CDC, which only tracks U.S. data.
What’s more notable than the number of cases is their rate of increase. In 2016, new cases increased by 175 percent and, on average, they have approximately doubled every year. From 2016 through 2022, the number of infections jumped from 63 to 2,377, a roughly 37-fold increase.
“This reminds me of what we saw with epidemics from 2013 through 2020… with Ebola, Zika and the COVID-19 pandemic,” says Robin Robinson, CEO of Spriovas and founding director of the Biomedical Advanced Research and Development Authority (BARDA), which is part of the U.S. Department of Health and Human Services. These epidemics started with a hockey stick trajectory, Robinson says—a gradual growth leading to a sharp spike, just like the shape of a hockey stick.
Another challenge is that right now medics don’t have rapid diagnostic tests for fungal infections. Currently, patients are often misdiagnosed because C. auris resembles several other easily treated fungi. Or they are diagnosed long after the infection begins and is harder to treat.
The problem is that existing diagnostics tests can only identify C. auris once it reaches the bloodstream. Yet, because this pathogen infects bodily tissues first, it should be possible to catch it much earlier before it becomes life-threatening. “We have to diagnose it before it reaches the bloodstream,” Walsh says.
The most alarming fact is that some Candida infections no longer respond to standard therapeutics.
“We need to focus on rapid diagnostic tests that do not rely on a positive blood culture,” says John Sperzel, president and CEO of T2 Biosystems, a company specializing in diagnostics solutions. Blood cultures typically take two to three days for the concentration of Candida to become large enough to detect. The company’s novel test detects about 90 percent of Candida species within three to five hours—thanks to its ability to spot minute quantities of the pathogen in blood samples instead of waiting for them to incubate and proliferate.
Unlike other Candida species C. auris thrives at human body temperatures
Adobe Stock
Tackling the resistance challenge
The most alarming fact is that some Candida infections no longer respond to standard therapeutics. The number of cases that stopped responding to echinocandin, the first-line therapy for most Candida infections, tripled in 2020, according to a study by the CDC.
Now, each of the first four clades shows varying levels of resistance to all three commonly prescribed classes of antifungal medications, such as azoles, echinocandins, and polyenes. For example, 97 percent of infections from C. auris Clade I are resistant to fluconazole, 54 percent to voriconazole and 30 percent of amphotericin. Nearly half are resistant to multiple antifungal drugs. Even with Clade II fungi, which has the least resistance of all the clades, 11 to 14 percent have become resistant to fluconazole.
Anti-fungal therapies typically target specific chemical compounds present on fungi’s cell membranes, but not on human cells—otherwise the medicine would cause damage to our own tissues. Fluconazole and other azole antifungals target a compound called ergosterol, preventing the fungal cells from replicating. Over the years, however, C. auris evolved to resist it, so existing fungal medications don’t work as well anymore.
A newer class of drugs called echinocandins targets a different part of the fungal cell. “The echinocandins – like caspofungin – inhibit (a part of the fungi) involved in making glucan, which is an essential component of the fungal cell wall and is not found in human cells,” Fernandes says. New antifungal treatments are needed, she adds, but there are only a few magic bullets that will hit just the fungus and not the human cells.
Research to fight infections also has been challenged by a lack of government support. That is changing now that BARDA is requesting proposals to develop novel antifungals. “The scope includes C. auris, as well as antifungals following a radiological/nuclear emergency, says BARDA spokesperson Elleen Kane.
The remaining challenge is the number of patients available to participate in clinical trials. Large numbers are needed, but the available patients are quite sick and often die before trials can be completed. Consequently, few biopharmaceutical companies are developing new treatments for C. auris.
ClinicalTrials.gov reports only two drugs in development for invasive C. auris infections—those than can spread throughout the body rather than localize in one particular area, like throat or vaginal infections: ibrexafungerp by Scynexis, Inc., fosmanogepix, by Pfizer.
Scynexis’ ibrexafungerp appears active against C. auris and other emerging, drug-resistant pathogens. The FDA recently approved it as a therapy for vaginal yeast infections and it is undergoing Phase III clinical trials against invasive candidiasis in an attempt to keep the infection from spreading.
“Ibreafungerp is structurally different from other echinocandins,” Fernandes says, because it targets a different part of the fungus. “We’re lucky it has activity against C. auris.”
Pfizer’s fosmanogepix is in Phase II clinical trials for patients with invasive fungal infections caused by multiple Candida species. Results are showing significantly better survival rates for people taking fosmanogepix.
Although C. auris does pose a serious threat to healthcare worldwide, scientists try to stay optimistic—because they recognized the problem early enough, they might have solutions in place before the perfect storm hits. “There is a bit of hope,” says Robinson. “BARDA has finally been able to fund the development of new antifungal agents and, hopefully, this year we can get several new classes of antifungals into development.”
New elevators could lift up our access to space
Story by Big Think
When people first started exploring space in the 1960s, it cost upwards of $80,000 (adjusted for inflation) to put a single pound of payload into low-Earth orbit.
A major reason for this high cost was the need to build a new, expensive rocket for every launch. That really started to change when SpaceX began making cheap, reusable rockets, and today, the company is ferrying customer payloads to LEO at a price of just $1,300 per pound.
This is making space accessible to scientists, startups, and tourists who never could have afforded it previously, but the cheapest way to reach orbit might not be a rocket at all — it could be an elevator.
The space elevator
The seeds for a space elevator were first planted by Russian scientist Konstantin Tsiolkovsky in 1895, who, after visiting the 1,000-foot (305 m) Eiffel Tower, published a paper theorizing about the construction of a structure 22,000 miles (35,400 km) high.
This would provide access to geostationary orbit, an altitude where objects appear to remain fixed above Earth’s surface, but Tsiolkovsky conceded that no material could support the weight of such a tower.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit.
In 1959, soon after Sputnik, Russian engineer Yuri N. Artsutanov proposed a way around this issue: instead of building a space elevator from the ground up, start at the top. More specifically, he suggested placing a satellite in geostationary orbit and dropping a tether from it down to Earth’s equator. As the tether descended, the satellite would ascend. Once attached to Earth’s surface, the tether would be kept taut, thanks to a combination of gravitational and centrifugal forces.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit. According to physicist Bradley Edwards, who researched the concept for NASA about 20 years ago, it’d cost $10 billion and take 15 years to build a space elevator, but once operational, the cost of sending a payload to any Earth orbit could be as low as $100 per pound.
“Once you reduce the cost to almost a Fed-Ex kind of level, it opens the doors to lots of people, lots of countries, and lots of companies to get involved in space,” Edwards told Space.com in 2005.
In addition to the economic advantages, a space elevator would also be cleaner than using rockets — there’d be no burning of fuel, no harmful greenhouse emissions — and the new transport system wouldn’t contribute to the problem of space junk to the same degree that expendable rockets do.
So, why don’t we have one yet?
Tether troubles
Edwards wrote in his report for NASA that all of the technology needed to build a space elevator already existed except the material needed to build the tether, which needs to be light but also strong enough to withstand all the huge forces acting upon it.
The good news, according to the report, was that the perfect material — ultra-strong, ultra-tiny “nanotubes” of carbon — would be available in just two years.
“[S]teel is not strong enough, neither is Kevlar, carbon fiber, spider silk, or any other material other than carbon nanotubes,” wrote Edwards. “Fortunately for us, carbon nanotube research is extremely hot right now, and it is progressing quickly to commercial production.”Unfortunately, he misjudged how hard it would be to synthesize carbon nanotubes — to date, no one has been able to grow one longer than 21 inches (53 cm).
Further research into the material revealed that it tends to fray under extreme stress, too, meaning even if we could manufacture carbon nanotubes at the lengths needed, they’d be at risk of snapping, not only destroying the space elevator, but threatening lives on Earth.
Looking ahead
Carbon nanotubes might have been the early frontrunner as the tether material for space elevators, but there are other options, including graphene, an essentially two-dimensional form of carbon that is already easier to scale up than nanotubes (though still not easy).
Contrary to Edwards’ report, Johns Hopkins University researchers Sean Sun and Dan Popescu say Kevlar fibers could work — we would just need to constantly repair the tether, the same way the human body constantly repairs its tendons.
“Using sensors and artificially intelligent software, it would be possible to model the whole tether mathematically so as to predict when, where, and how the fibers would break,” the researchers wrote in Aeon in 2018.
“When they did, speedy robotic climbers patrolling up and down the tether would replace them, adjusting the rate of maintenance and repair as needed — mimicking the sensitivity of biological processes,” they continued.Astronomers from the University of Cambridge and Columbia University also think Kevlar could work for a space elevator — if we built it from the moon, rather than Earth.
They call their concept the Spaceline, and the idea is that a tether attached to the moon’s surface could extend toward Earth’s geostationary orbit, held taut by the pull of our planet’s gravity. We could then use rockets to deliver payloads — and potentially people — to solar-powered climber robots positioned at the end of this 200,000+ mile long tether. The bots could then travel up the line to the moon’s surface.
This wouldn’t eliminate the need for rockets to get into Earth’s orbit, but it would be a cheaper way to get to the moon. The forces acting on a lunar space elevator wouldn’t be as strong as one extending from Earth’s surface, either, according to the researchers, opening up more options for tether materials.
“[T]he necessary strength of the material is much lower than an Earth-based elevator — and thus it could be built from fibers that are already mass-produced … and relatively affordable,” they wrote in a paper shared on the preprint server arXiv.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one.
Electrically powered climber capsules could go up down the tether to deliver payloads to any Earth orbit.
Adobe Stock
Some Chinese researchers, meanwhile, aren’t giving up on the idea of using carbon nanotubes for a space elevator — in 2018, a team from Tsinghua University revealed that they’d developed nanotubes that they say are strong enough for a tether.
The researchers are still working on the issue of scaling up production, but in 2021, state-owned news outlet Xinhua released a video depicting an in-development concept, called “Sky Ladder,” that would consist of space elevators above Earth and the moon.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one. If the project could be pulled off — a huge if — China predicts Sky Ladder could cut the cost of sending people and goods to the moon by 96 percent.
The bottom line
In the 120 years since Tsiolkovsky looked at the Eiffel Tower and thought way bigger, tremendous progress has been made developing materials with the properties needed for a space elevator. At this point, it seems likely we could one day have a material that can be manufactured at the scale needed for a tether — but by the time that happens, the need for a space elevator may have evaporated.
Several aerospace companies are making progress with their own reusable rockets, and as those join the market with SpaceX, competition could cause launch prices to fall further.
California startup SpinLaunch, meanwhile, is developing a massive centrifuge to fling payloads into space, where much smaller rockets can propel them into orbit. If the company succeeds (another one of those big ifs), it says the system would slash the amount of fuel needed to reach orbit by 70 percent.
Even if SpinLaunch doesn’t get off the ground, several groups are developing environmentally friendly rocket fuels that produce far fewer (or no) harmful emissions. More work is needed to efficiently scale up their production, but overcoming that hurdle will likely be far easier than building a 22,000-mile (35,400-km) elevator to space.