The Promise of Pills That Know When You Swallow Them
A woman prepares to swallow a digital pill that can track whether she has taken her medication.
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."
New Podcast: George Church on Woolly Mammoths, Organ Transplants, and Covid Vaccines
Dr. George Church, a leading pioneer of gene editing, updates our listeners on several of his noteworthy projects.
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
This month, our guest is notable genetics pioneer Dr. George Church of Harvard Medical School. Dr. Church has remarkably bold visions for how innovation in science can fundamentally transform the future of humanity and our planet. His current moonshot projects include: de-extincting some of the woolly mammoth's genes to create a hybrid Asian elephant with the cold-tolerance traits of the woolly mammoth, so that this animal can re-populate the Arctic and help stave off climate change; reversing chronic diseases of aging through gene therapy, which he and colleagues are now testing in dogs; and transplanting genetically engineered pig organs to humans to eliminate the tragically long waiting lists for organs. Hear Dr. Church discuss all this and more on our latest episode.
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Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Beyond Henrietta Lacks: How the Law Has Denied Every American Ownership Rights to Their Own Cells
A 2017 portrait of Henrietta Lacks.
The common perception is that Henrietta Lacks was a victim of poverty and racism when in 1951 doctors took samples of her cervical cancer without her knowledge or permission and turned them into the world's first immortalized cell line, which they called HeLa. The cell line became a workhorse of biomedical research and facilitated the creation of medical treatments and cures worth untold billions of dollars. Neither Lacks nor her family ever received a penny of those riches.
But racism and poverty is not to blame for Lacks' exploitation—the reality is even worse. In fact all patients, then and now, regardless of social or economic status, have absolutely no right to cells that are taken from their bodies. Some have called this biological slavery.
How We Got Here
The case that established this legal precedent is Moore v. Regents of the University of California.
John Moore was diagnosed with hairy-cell leukemia in 1976 and his spleen was removed as part of standard treatment at the UCLA Medical Center. On initial examination his physician, David W. Golde, had discovered some unusual qualities to Moore's cells and made plans prior to the surgery to have the tissue saved for research rather than discarded as waste. That research began almost immediately.
"On both sides of the case, legal experts and cultural observers cautioned that ownership of a human body was the first step on the slippery slope to 'bioslavery.'"
Even after Moore moved to Seattle, Golde kept bringing him back to Los Angeles to collect additional samples of blood and tissue, saying it was part of his treatment. When Moore asked if the work could be done in Seattle, he was told no. Golde's charade even went so far as claiming to find a low-income subsidy to pay for Moore's flights and put him up in a ritzy hotel to get him to return to Los Angeles, while paying for those out of his own pocket.
Moore became suspicious when he was asked to sign new consent forms giving up all rights to his biological samples and he hired an attorney to look into the matter. It turned out that Golde had been lying to his patient all along; he had been collecting samples unnecessary to Moore's treatment and had turned them into a cell line that he and UCLA had patented and already collected millions of dollars in compensation. The market for the cell lines was estimated at $3 billion by 1990.
Moore felt he had been taken advantage of and filed suit to claim a share of the money that had been made off of his body. "On both sides of the case, legal experts and cultural observers cautioned that ownership of a human body was the first step on the slippery slope to 'bioslavery,'" wrote Priscilla Wald, a professor at Duke University whose career has focused on issues of medicine and culture. "Moore could be viewed as asking to commodify his own body part or be seen as the victim of the theft of his most private and inalienable information."
The case bounced around different levels of the court system with conflicting verdicts for nearly six years until the California Supreme Court ruled on July 9, 1990 that Moore had no legal rights to cells and tissue once they were removed from his body.
The court made a utilitarian argument that the cells had no value until scientists manipulated them in the lab. And it would be too burdensome for researchers to track individual donations and subsequent cell lines to assure that they had been ethically gathered and used. It would impinge on the free sharing of materials between scientists, slow research, and harm the public good that arose from such research.
"In effect, what Moore is asking us to do is impose a tort duty on scientists to investigate the consensual pedigree of each human cell sample used in research," the majority wrote. In other words, researchers don't need to ask any questions about the materials they are using.
One member of the court did not see it that way. In his dissent, Stanley Mosk raised the specter of slavery that "arises wherever scientists or industrialists claim, as defendants have here, the right to appropriate and exploit a patient's tissue for their sole economic benefit—the right, in other words, to freely mine or harvest valuable physical properties of the patient's body. … This is particularly true when, as here, the parties are not in equal bargaining positions."
Mosk also cited the appeals court decision that the majority overturned: "If this science has become for profit, then we fail to see any justification for excluding the patient from participation in those profits."
But the majority bought the arguments that Golde, UCLA, and the nascent biotechnology industry in California had made in amici briefs filed throughout the legal proceedings. The road was now cleared for them to develop products worth billions without having to worry about or share with the persons who provided the raw materials upon which their research was based.
Critical Views
Biomedical research requires a continuous and ever-growing supply of human materials for the foundation of its ongoing work. If an increasing number of patients come to feel as John Moore did, that the system is ripping them off, then they become much less likely to consent to use of their materials in future research.
Some legal and ethical scholars say that donors should be able to limit the types of research allowed for their tissues and researchers should be monitored to assure compliance with those agreements. For example, today it is commonplace for companies to certify that their clothing is not made by child labor, their coffee is grown under fair trade conditions, that food labeled kosher is properly handled. Should we ask any less of our pharmaceuticals than that the donors whose cells made such products possible have been treated honestly and fairly, and share in the financial bounty that comes from such drugs?
Protection of individual rights is a hallmark of the American legal system, says Lisa Ikemoto, a law professor at the University of California Davis. "Putting the needs of a generalized public over the interests of a few often rests on devaluation of the humanity of the few," she writes in a reimagined version of the Moore decision that upholds Moore's property claims to his excised cells. The commentary is in a chapter of a forthcoming book in the Feminist Judgment series, where authors may only use legal precedent in effect at the time of the original decision.
"Why is the law willing to confer property rights upon some while denying the same rights to others?" asks Radhika Rao, a professor at the University of California, Hastings College of the Law. "The researchers who invest intellectual capital and the companies and universities that invest financial capital are permitted to reap profits from human research, so why not those who provide the human capital in the form of their own bodies?" It might be seen as a kind of sweat equity where cash strapped patients make a valuable in kind contribution to the enterprise.
The Moore court also made a big deal about inhibiting the free exchange of samples between scientists. That has become much less the situation over the more than three decades since the decision was handed down. Ironically, this decision, as well as other laws and regulations, have since strengthened the power of patents in biomedicine and by doing so have increased secrecy and limited sharing.
"Although the research community theoretically endorses the sharing of research, in reality sharing is commonly compromised by the aggressive pursuit and defense of patents and by the use of licensing fees that hinder collaboration and development," Robert D. Truog, Harvard Medical School ethicist and colleagues wrote in 2012 in the journal Science. "We believe that measures are required to ensure that patients not bear all of the altruistic burden of promoting medical research."
Additionally, the increased complexity of research and the need for exacting standardization of materials has given rise to an industry that supplies certified chemical reagents, cell lines, and whole animals bred to have specific genetic traits to meet research needs. This has been more efficient for research and has helped to ensure that results from one lab can be reproduced in another.
The Court's rationale of fostering collaboration and free exchange of materials between researchers also has been undercut by the changing structure of that research. Big pharma has shrunk the size of its own research labs and over the last decade has worked out cooperative agreements with major research universities where the companies contribute to the research budget and in return have first dibs on any findings (and sometimes a share of patent rights) that come out of those university labs. It has had a chilling effect on the exchange of materials between universities.
Perhaps tracking cell line donors and use restrictions on those donations might have been burdensome to researchers when Moore was being litigated. Some labs probably still kept their cell line records on 3x5 index cards, computers were primarily expensive room-size behemoths with limited capacity, the internet barely existed, and there was no cloud storage.
But that was the dawn of a new technological age and standards have changed. Now cell lines are kept in state-of-the-art sub zero storage units, tagged with the source, type of tissue, date gathered and often other information. Adding a few more data fields and contacting the donor if and when appropriate does not seem likely to disrupt the research process, as the court asserted.
Forging the Future
"U.S. universities are awarded almost 3,000 patents each year. They earn more than $2 billion each year from patent royalties. Sharing a modest portion of these profits is a novel method for creating a greater sense of fairness in research relationships that we think is worth exploring," wrote Mark Yarborough, a bioethicist at the University of California Davis Medical School, and colleagues. That was penned nearly a decade ago and those numbers have only grown.
The Michigan BioTrust for Health might serve as a useful model in tackling some of these issues. Dried blood spots have been collected from all newborns for half a century to be tested for certain genetic diseases, but controversy arose when the huge archive of dried spots was used for other research projects. As a result, the state created a nonprofit organization to in essence become a biobank and manage access to these spots only for specific purposes, and also to share any revenue that might arise from that research.
"If there can be no property in a whole living person, does it stand to reason that there can be no property in any part of a living person? If there were, can it be said that this could equate to some sort of 'biological slavery'?" Irish ethicist Asim A. Sheikh wrote several years ago. "Any amount of effort spent pondering the issue of 'ownership' in human biological materials with existing law leaves more questions than answers."
Perhaps the biggest question will arise when -- not if but when -- it becomes possible to clone a human being. Would a human clone be a legal person or the property of those who created it? Current legal precedent points to it being the latter.
Today, October 4, is the 70th anniversary of Henrietta Lacks' death from cancer. Over those decades her immortalized cells have helped make possible miraculous advances in medicine and have had a role in generating billions of dollars in profits. Surviving family members have spoken many times about seeking a share of those profits in the name of social justice; they intend to file lawsuits today. Such cases will succeed or fail on their own merits. But regardless of their specific outcomes, one can hope that they spark a larger public discussion of the role of patients in the biomedical research enterprise and lead to establishing a legal and financial claim for their contributions toward the next generation of biomedical research.