The same way that it's harder to lose 100 pounds than it is to not gain 100 pounds, it's easier to stop a disease before it happens than to treat an illness once it's developed.
In Morris' dream scenario "everyone will be implanted with a sensor" ("…the same way most people are vaccinated") and the sensor will alert people to go to the doctor if something is awry.
Bio-engineers working on the next generation of diagnostic tools say today's technology, such as colonoscopies or mammograms, are reactionary; that is, they tell a person they are sick often when it's too late to reverse course. Surveillance medicine — such as implanted sensors — will detect disease at its onset, in real time.
What Is Possible?
Ever since the Human Genome Project — which concluded in 2003 after mapping the DNA sequence of all 30,000 human genes — modern medicine has shifted to "personalized medicine." Also called, "precision health," 21st-century doctors can in some cases assess a person's risk for specific diseases from his or her DNA. The information enables women with a BRCA gene mutation, for example, to undergo more frequent screenings for breast cancer or to pro-actively choose to remove their breasts, as a "just in case" measure.
But your DNA is not always enough to determine your risk of illness. Not all genetic mutations are harmful, for example, and people can get sick without a genetic cause, such as with an infection. Hence the need for a more "real-time" way to monitor health.
Aaron Morris, a postdoctoral researcher in the Department of Biomedical Engineering at the University of Michigan, wants doctors to be able to predict illness with pinpoint accuracy well before symptoms show up. Working in the lab of Dr. Lonnie Shea, the team is building "a tiny diagnostic lab" that can live under a person's skin and monitor for illness, 24/7. Currently being tested in mice, the Michigan team's porous biodegradable implant becomes part of the body as "cells move right in," says Morris, allowing engineered tissue to be biopsied and analyzed for diseases. The information collected by the sensors will enable doctors to predict disease flareups, such as for cancer relapses, so that therapies can begin well before a person comes out of remission. The technology will also measure the effectiveness of those therapies in real time.
In Morris' dream scenario "everyone will be implanted with a sensor" ("…the same way most people are vaccinated") and the sensor will alert people to go to the doctor if something is awry.
While it may be four or five decades before Morris' sensor becomes mainstream, "the age of surveillance medicine is here," says Jamie Metzl, a technology and healthcare futurist who penned Hacking Darwin: Genetic Engineering and the Future of Humanity. "It will get more effective and sophisticated and less obtrusive over time," says Metzl.
Already, Google compiles public health data about disease hotspots by amalgamating individual searches for medical symptoms; pill technology can digitally track when and how much medication a patient takes; and, the Apple watch heart app can predict with 85-percent accuracy if an individual using the wrist device has Atrial Fibrulation (AFib) — a condition that causes stroke, blood clots and heart failure, and goes undiagnosed in 700,000 people each year in the U.S.
"We'll never be able to predict everything," says Metzl. "But we will always be able to predict and prevent more and more; that is the future of healthcare and medicine."
Morris believes that within ten years there will be surveillance tools that can predict if an individual has contracted the flu well before symptoms develop.
At City College of New York, Ryan Williams, assistant professor of biomedical engineering, has built an implantable nano-sensor that works with a florescent wand to scope out if cancer cells are growing at the implant site. "Instead of having the ovary or breast removed, the patient could just have this [surveillance] device that can say 'hey we're monitoring for this' in real-time… [to] measure whether the cancer is maybe coming back,' as opposed to having biopsy tests or undergoing treatments or invasive procedures."
Not all surveillance technologies that are being developed need to be implanted. At Case Western, Colin Drummond, PhD, MBA, a data scientist and assistant department chair of the Department of Biomedical Engineering, is building a "surroundable." He describes it as an Alexa-style surveillance system (he's named her Regina) that will "tell" the user, if a need arises for medication, how much to take and when.
Bioethical Red Flags
"Everyone should be extremely excited about our move toward what I call predictive and preventive health care and health," says Metzl. "We should also be worried about it. Because all of these technologies can be used well and they can [also] be abused." The concerns are many layered:
For years now, bioethicists have expressed concerns about employee-sponsored wellness programs that encourage fitness while also tracking employee health data."Getting access to your health data can change the way your employer thinks about your employability," says Keisha Ray, assistant professor at the University of Texas Health Science Center at Houston (UTHealth). Such access can lead to discriminatory practices against employees that are less fit. "Surveillance medicine only heightens those risks," says Ray.
Who owns the data?
Surveillance medicine may help "democratize healthcare" which could be a good thing, says Anita Ho, an associate professor in bioethics at both the University of California, San Francisco and at the University of British Columbia. It would enable easier access by patients to their health data, delivered to smart phones, for example, rather than waiting for a call from the doctor. But, she also wonders who will own the data collected and if that owner has the right to share it or sell it. "A direct-to-consumer device is where the lines get a little blurry," says Ho. Currently, health data collected by Apple Watch is owned by Apple. "So we have to ask bigger ethical questions in terms of what consent should be required" by users.
"Consumers of these products deserve some sort of assurance that using a product that will predict future needs won't in any way jeopardize their ability to access care for those needs," says Hastings Center bioethicist Carolyn Neuhaus. She is urging lawmakers to begin tackling policy issues created by surveillance medicine, now, well ahead of the technology becoming mainstream, not unlike GINA, the Genetic Information Nondiscrimination Act of 2008 -- a federal law designed to prevent discrimination in health insurance on the basis of genetic information.
And, because not all Americans have insurance, Ho wants to know, who's going to pay for this technology and how much will it cost?
Trusting our guts
Some bioethicists are concerned that surveillance technology will reduce individuals to their "risk profiles," leaving health care systems to perceive them as nothing more than a "bundle of health and security risks." And further, in our quest to predict and prevent ailments, Neuhaus wonders if an over-reliance on data could damage the ability of future generations to trust their gut and tune into their own bodies?
It "sounds kind of hippy-dippy and feel-goodie," she admits. But in our culture of medicine where efficiency is highly valued, there's "a tendency to not value and appreciate what one feels inside of their own body … [because] it's easier to look at data than to listen to people's really messy stories of how they 'felt weird' the other day. It takes a lot less time to look at a sheet, to read out what the sensor implanted inside your body or planted around your house says."
Ho, too, worries about lost narratives. "For surveillance medicine to actually work we have to think about how we educate clinicians about the utility of these devices and how to how to interpret the data in the broader context of patients' lives."
While one of the goals of surveillance medicine is to cut down on doctor visits, Ho wonders if the technology will have the opposite effect. "People may be going to the doctor more for things that actually are benign and are really not of concern yet," says Ho. She is also concerned that surveillance tools could make healthcare almost "recreational" and underscores the importance of making sure that the goals of surveillance medicine are met before the technology is unleashed.
"We can't just assume that any of these technologies are inherently technologies of liberation."
AI doesn't fix existing healthcare problems
"Knowing that you're going to have a fall or going to relapse or have a disease isn't all that helpful if you have no access to the follow-up care and you can't afford it and you can't afford the prescription medication that's going to ward off the onset," says Neuhaus. "It may still be worth knowing … but we can't fool ourselves into thinking that this technology is going to reshape medicine in America if we don't pay attention to … the infrastructure that we don't currently have."
How surveillances devices are tested before being approved for human use is a major concern for Ho. In recent years, alerts have been raised about the homogeneity of study group participants — too white and too male. Ho wonders if the devices will be able to "accurately predict the disease progression for people whose data has not been used in developing the technology?" COVID-19 has killed Black people at a rate 2.5 time greater than white people, for example, and new, virtual clinical research is focused on recruiting more people of color.
The Biggest Question
"We can't just assume that any of these technologies are inherently technologies of liberation," says Metzl.
Especially because we haven't yet asked the 64-thousand dollar question: Would patients even want to know?
Jenny Ahlstrom is an IT professional who was diagnosed at 43 with multiple myeloma, a blood cancer that typically attacks people in their late 60s and 70s and for which there is no cure. She believes that most people won't want to know about their declining health in real time. People like to live "optimistically in denial most of the time. If they don't have a problem, they don't want to really think they have a problem until they have [it]," especially when there is no cure. "Psychologically? That would be hard to know."
Ahlstrom says there's also the issue of trust, something she experienced first-hand when she launched her non-profit, HealthTree, a crowdsourcing tool to help myeloma patients "find their genetic twin" and learn what therapies may or may not work. "People want to share their story, not their data," says Ahlstrom. "We have been so conditioned as a nation to believe that our medical data is so valuable."
Metzl acknowledges that adoption of new technologies will be uneven. But he also believes that "over time, it will be abundantly clear that it's much, much cheaper to predict and prevent disease than it is to treat disease once it's already emerged."
Beyond cost, the tremendous potential of these technologies to help us live healthier and longer lives is a game-changer, he says, as long as we find ways "to ultimately navigate this terrain and put systems in place ... to minimize any potential harms."
Every year, one in seven people in America comes down with a foodborne illness, typically caused by a bacterial pathogen, including E.Coli, listeria, salmonella, or campylobacter. That adds up to 48 million people, of which 120,000 are hospitalized and 3000 die, according to the Centers for Disease Control. And the variety of foods that can be contaminated with bacterial pathogens is growing too. In the 20th century, E.Coli and listeria lurked primarily within meat. Now they find their way into lettuce, spinach, and other leafy greens, causing periodic consumer scares and product recalls. Onions are the most recent suspected culprit of a nationwide salmonella outbreak.
Some of these incidents are almost inevitable because of how Mother Nature works, explains Divya Jaroni, associate professor of animal and food sciences at Oklahoma State University. These common foodborne pathogens come from the cattle's intestines when the animals shed them in their manure—and then they get washed into rivers and lakes, especially in heavy rains. When this water is later used to irrigate produce farms, the bugs end up on salad greens. Plus, many small farms do both—herd cattle and grow produce.
"Unfortunately for us, these pathogens are part of the microflora of the cows' intestinal tract," Jaroni says. "Some farmers may have an acre or two of cattle pastures, and an acre of a produce farm nearby, so it's easy for this water to contaminate the crops."
Food producers and packagers fight bacteria by potent chemicals, with chlorine being the go-to disinfectant. Cattle carcasses, for example, are typically washed by chlorine solutions as the animals' intestines are removed. Leafy greens are bathed in water with added chlorine solutions. However, because the same "bath" can be used for multiple veggie batches and chlorine evaporates over time, the later rounds may not kill all of the bacteria, sparing some. The natural and organic producers avoid chlorine, substituting it with lactic acid, a more holistic sanitizer, but even with all these efforts, some pathogens survive, sickening consumers and causing food recalls. As we farm more animals and grow more produce, while also striving to use fewer chemicals and more organic growing methods, it will be harder to control bacteria's spread.
"It took us a long time to convince the FDA phages were safe and efficient alternatives. But we had worked with them to gather all the data they needed, and the FDA was very supportive in the end."
Luckily, bacteria have their own killers. Called bacteriophages, or phages for short, they are viruses that prey on bacteria only. Under the electron microscope, they look like fantasy spaceships, with oblong bodies, spider-like legs and long tails. Much smaller than a bacterium, phages pierce the microbes' cells with their tails, sneak in and begin multiplying inside, eventually bursting the microbes open—and then proceed to infect more of them. The best part is that these phages are harmless to humans. Moreover, recent research finds that millions of phages dwell on us and in us—in our nose, throat, skin and gut, protecting us from bacterial infections as part of our healthy microbiome. A recent study suggested that we absorb about 30 billion phages into our bodies on a daily basis. Now, ingeniously, they are starting to be deployed as anti-microbial agents in the food industry.
A Maryland-based phage research company called Intralytix is doing just that. Founded by Alexander Sulakvelidze, a microbiologist and epidemiologist who came to the United States from Tbilisi, the capital of Georgia, Intralytix makes and sells five different FDA-approved phage cocktails that work against some of the most notorious food pathogens: ListShield for Listeria, SalmoFresh for Salmonella, ShigaShield for Shigella, another foodborne bug, and EcoShield for E.coli, including the infamous strain that caused the Jack in the Box outbreak in 1993 that killed four children and sickened 732 people across four states. Earlier this month, the FDA granted its approval to yet another Intralytix phage for managing Campylobacter contamination, named CampyShield. "We call it safety by nature," Sulakvelidze says.
Intralytix grows phages inside massive 1500-liter fermenters, feeding them bacterial "fodder."
Photo credit: Living Radiant Photography
Phage preparations are relatively straightforward to make. In nature, phages thrive in any body of water where bacteria live too, including rivers, lakes and bays. "I can dip a bucket into the Chesapeake Bay, and it will be full of all kinds of phages," Sulakvelidze says. "Sewage is another great place to look for specific phages of interest, because it's teeming with all sorts of bacteria—and therefore the viruses that prey on them." In lab settings, Intralytix grows phages inside massive 1500-liter fermenters, feeding them bacterial "fodder." Once phages multiply enough, they are harvested, dispensed into containers and shipped to food producers who have adopted this disinfecting practice into their preparation process. Typically, it's done by computer-controlled sprayer systems that disperse mist-like phage preparations onto the food.
Unlike chemicals like chlorine or antibiotics, which kill a wide spectrum of bacteria, phages are more specialized, each feeding on specific microbial species. A phage that targets salmonella will not prey on listeria and vice versa. So food producers may sometimes use a combo of different phage preparations. Intralytix is continuously researching and testing new phages. With a contract from the National Institutes of Health, Intralytix is expanding its automated high-throughput robot that tests which phages work best against which bacteria, speeding up the development of the new phage cocktails.
Phages have other "talents." In her recent study, Jaroni found that phages have the ability to destroy bacterial biofilms—colonies of microorganisms that tend to grow on surfaces of the food processing equipment, surrounding themselves with protective coating that even very harsh chemicals can't crack. "Phages are very clever," Jaroni says. "They produce enzymes that target the biofilms, and once they break through, they can reach the bacteria."
Convincing the FDA that phages were safe to use on food products was no easy feat, Sulakvelidze says. In his home country of Georgia, phages have been used as antimicrobial remedies for over a century, but the FDA was leery of using viruses as food safety agents. "It took us a long time to convince the FDA phages were safe and efficient alternatives," Sulakvelidze says. "But we had worked with them to gather all the data they needed, and the FDA was very supportive in the end." The agency had granted Intralytix its first approval in 2006, and over the past 10 years, the company's sales increased by over 15-fold. "We currently sell to about 40 companies and are in discussions with several other large food producers," Sulakvelidze says. One indicator that the industry now understands and appreciates the science of phages was that his company was ranked as Top Food Safety Provider in 2021 by Food and Beverage Technology Review, he adds. Notably, phage sprays are kosher, halal and organic-certified.
Intralytix's phage cocktails to safeguard food from bacteria are approved for consumers in addition to food producers, but currently the company sells to food producers only. Selling retail requires different packaging like easy-to-use spray bottles and different marketing that would inform people about phages' antimicrobial qualities. But ultimately, giving people the ability to remove pathogens from their food with probiotic phage sprays is the goal, Sulakvelidze says.
It's not the company's only goal. Now Intralytix is going a step further, investigating phages' probiotic and therapeutic abilities. Because phages are highly specialized in the bacteria they target, they can be used to treat infections caused by specific pathogens while leaving the beneficial species of our microbiome intact. In an ongoing clinical trial with Mount Sinai, Intralytix is now investigating a potential phage treatment against a certain type of E. coli for patients with Crohn's disease, and is about to start another clinical trial for treating bacterial dysentery.
"Now that we have proved that phages are safe and effective against foodborne bacteria," Sulakvelidze says, "we are going to demonstrate their potential in therapeutic applications."
In 2014, the city of Flint, Michigan switched the residents' water supply to the Flint river, citing cheaper costs. However, due to improper filtering, lead contaminated this water, and according to the Associated Press, many of the city's residents soon reported health issues like hair loss and rashes. In 2015, a report found that children there had high levels of lead in their blood. The National Resource Defense Council recently discovered there could still be as many as twelve million lead pipes carrying water to homes across the U.S.
What if Flint residents and others in afflicted areas could simply flick water onto their phone screens and an app would tell them if they were about to drink contaminated water? This is what researchers at the University of Cambridge are working on to prevent catastrophes like what occurred in Flint, and to prepare for an uncertain future of scarcer resources.
Underneath the tough glass of our phone screen lies a transparent layer of electrodes. Because our bodies hold an electric charge, when our finger touches the screen, it disrupts the electric field created among the electrodes. This is how the screen can sense where a touch occurs. Cambridge scientists used this same idea to explore whether the screen could detect charges in water, too. Metals like arsenic and lead can appear in water in the form of ions, which are charged particles. When the ionic solution is placed on the screen's surface, the electrodes sense that charge like how they sense our finger.
Imagine a new generation of smartphones with a designated area of the screen responsible for detecting contamination—this is one of the possible futures the researchers propose.
The experiment measured charges in various electrolyte solutions on a touchscreen. The researchers found that a thin polymer layer between the electrodes and the sample solution helped pick up the charges.
"How can we get really close to the touch electrodes, and be better than a phone screen?" Horstmann, the lead scientist on the study, asked himself while designing the protective coating. "We found that when we put electrolytes directly on the electrodes, they were too close, even short-circuiting," he said. When they placed the polymer layer on top the electrodes, however, this short-circuiting did not occur. Horstmann speaks of the polymer layer as one of the key findings of the paper, as it allowed for optimum conductivity. The coating they designed was much thinner than what you'd see with a typical smartphone touchscreen, but because it's already so similar, he feels optimistic about the technology's practical applications in the real world.
While the Cambridge scientists were using touchscreens to measure water contamination, Dr. Baojun Wang, a synthetic biologist at the University of Edinburgh, along with his team, created a way to measure arsenic contamination in Bangladesh groundwater samples using what is called a cell-based biosensor. These biosensors use cornerstones of cellular activity like transcription and promoter sequences to detect the presence of metal ions in water. A promoter can be thought of as a "flag" that tells certain molecules where to begin copying genetic code. By hijacking this aspect of the cell's machinery and increasing the cell's sensing and signal processing ability, they were able to amplify the signal to detect tiny amounts of arsenic in the groundwater samples. All this was conducted in a 384-well plate, each well smaller than a pencil eraser.
They placed arsenic sensors with different sensitivities across part of the plate so it resembled a volume bar of increasing levels of arsenic, similar to diagnostics on a Fitbit or glucose monitor. The whole device is about the size of an iPhone, and can be scaled down to a much smaller size.
Dr. Wang says cell-based biosensors are bringing sensing technology closer to field applications, because their machinery uses inherent cellular activity. This makes them ideal for low-resource communities, and he expects his device to be affordable, portable, and easily stored for widespread use in households.
"It hasn't worked on actual phones yet, but I don't see any reason why it can't be an app," says Horstmann of their technology. Imagine a new generation of smartphones with a designated area of the screen responsible for detecting contamination—this is one of the possible futures the researchers propose. But industry collaborations will be crucial to making their advancements practical. The scientists anticipate that without collaborative efforts from the business sector, the public might have to wait ten years until this becomes something all our smartphones are capable of—but with the right partners, "it could go really quickly," says Dr. Elizabeth Hall, one of the authors on the touchscreen water contamination study.
"That's where the science ends and the business begins," Dr. Hall says. "There is a lot of interest coming through as a result of this paper. I think the people who make the investments and decisions are seeing that there might be something useful here."
As for Flint, according to The Detroit News, the city has entered the final stages in removing lead pipe infrastructure. It's difficult to imagine how many residents might fare better today if they'd had the technology that scientists are now creating.
Of all its tragedy, COVID-19 has increased demand for at-home testing methods, which has carried over to non-COVID-19-related devices. Various testing efforts are now in the public eye.
"I like that the public is watching these directions," says Horstmann. "I think there's a long way to go still, but it's exciting."