As new variants of the coronavirus continue to spring up like wildfires across the planet, researchers have been frantically trying to determine which new strains might outwit our brand new vaccines.
Artificial intelligence (AI) may be able to help. In a paper published Friday in the journal Science, researchers at MIT described a machine learning algorithm that can predict which mutations pose the biggest threat to the world’s fledgling immunity.
The tool could be used to quickly narrow down which mutations are most likely to evade the immune systems of people who have been vaccinated or previously infected. Researchers can then test suspected strains in the lab and update vaccines accordingly.
“This is a real-time companion to vaccine development,” says Bryan Bryson, a biological engineer at MIT and co-author of the paper. “What we can do with our model right now is a lot faster than what you can do in the lab.”
As new, more contagious variants of the coronavirus surge across the planet, public health officials are scrambling to increase genetic sequencing of positive samples. Sequencing is crucial in understanding how the virus is changing, and determining whether our brand new vaccines will remain effective, officials say.
“Imagine if we didn’t have this genetic data,” says Richard Neher, a professor at the University of Basel who studies the genetic evolution of viruses. “We would see a surge in cases without having any idea what might have changed.”
While the variants are likely more contagious, there is no evidence suggesting that they are more deadly or cause more severe disease. Many experts also say that the COVID-19 vaccines that have already been developed will still be effective against the new variants. Still, global surveillance of the virus’s genetic sequence is needed to stay on top of the virus’s continual adaptations, and plan a vaccine response.
What are viral variants?
Viruses, including SARS-CoV-2 (the coronavirus that causes COVID-19), are constantly mutating. As they move from person to person, their genetic code changes slightly. Most of these mutations are inconsequential, producing no meaningful changes to the structure or function of the virus.
As a virus moves through populations of people, it begins to accumulate enough mutations to lead researchers to call it a “variant” and give it a name. Many variants of the coronavirus have already been recognized.
Sometimes multiple mutations occur quickly, as was the case with the B.1.1.7 variant in the UK. Neher, who helps track the genetic changes in viruses using the software tool Nextstrain, estimates that B.1.1.7 is about 30-35 mutations away from the original strain detected in Wuhan, China at the beginning of the pandemic. Between 10 and 17 of those mutations appeared suddenly, compared with the virus’s most recent ancestor.
Many of B.1.1.7’s mutations occur in areas of the genome that code for elements of the virus’s spike protein. That’s important, because the virus’s spike protein is what it uses to enter human cells. It’s also what our immune systems will recognize when attacking the virus.
Will approved vaccines work against the new variants?
The more the spike protein changes, the harder it is for the immune systems of people who have been vaccinated to mount a swift attack. The same goes for people who have already had COVID-19—their immune systems know the spike protein of the older variants.
But it takes a lot of genetic changes to the spike protein before it can evade our complex immune systems. “The spike protein is a large protein,” says Neher. “It’s not like a single mutation there would change the virus in a way that it can re-infect everybody on the planet. It’s a more of gradual process where some mutations might reduce efficacy of the immune response in some fraction of the population.”
The section of the genome that codes for the spike protein is about 3,800 nucleotides, or units, long. So even with a dozen mutations, “for all intents and purposes, it’s the same protein,” says Neher.
Many experts, including those at the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. National institute of Allergy and Infectious Diseases, have stated publicly that our current vaccines will most likely be effective against the latest variants.
The mutations are “unlikely to have a large impact on vaccine-induced immunity or on existing immunity” from previous infection, said Greg Armstrong, director of the advanced molecular detection program at the CDC, in a media briefing last week.
If the variants do start to evade immune systems of vaccinated people, vaccines can be altered to mimic the new variants. mRNA-based vaccines, such as those developed by Moderna and Pfizer/BioNTech, can be adjusted relatively quickly.
Public health experts push for more genetic sequencing
But to be sure, the public health community will have to keep a close eye on the variants, as well as the virus’s future adaptions, which will undoubtedly occur. To that end, experts are calling for larger, more coordinated genetic sequencing and epidemiological surveillance.
In a statement posted December 31, the World Health Organization (WHO) advised the world to “increase routine systematic sequencing of SARS-CoV-2 viruses to better understand SARS-CoV-2 transmission and to monitor for the emergence of variants.”
Still, more is needed. On December 29, the CDC said that the U.S. had about 51,000 sequences in its public databases, noting that the UK had more than twice that many. The CDC now aims to scale up to 3,500 whole genome sequences per week, according to Armstrong at the CDC.
To do that, the agency in November launched the National SARS-CoV-2 Strain Surveillance (NS3) program, and asked each U.S. state to send at least ten samples biweekly for sequencing. The agency is also funding and working with national reference labs and local academic centers to increase sequencing.
Armstrong’s division has also been working since 2014 to integrate next-generation sequencing and bioinformatics expertise into state and local health departments. It increased funding for that in December. The effort includes training people to use portable, desktop genetic sequencers such as Oxford Nanopore’s MinION and Illumina’s MiniSeq.
In a triumph of science, the first two large-scale trials to report the effectiveness of vaccines against SARS-CoV-2—the deadly, highly contagious virus that causes COVID-19—were both great successes right out of the gate. In November, the pharmaceutical giant Pfizer and the much younger biotech company Moderna both reported that their vaccines were about 95 percent effective in preventing cases of COVID-19. The news came just 10 months after the virus was first isolated and sequenced in a lab in China.
As of early December, 50 other candidate vaccines were making their way through human clinical trials, according to the World Health Organization. Thirteen of those vaccines were already in the final stage before approval, each being tested on tens of thousands of volunteers to check for side effects and measure efficacy: how well the shots protect against the disease. One of those, made by AstraZeneca and the University of Oxford, also showed promising—though less clear—efficacy results in late November.
But even before those vaccines neared the finish line, the heaviest burdens of ending the pandemic and restoring the global economy had shifted from the scientists to the engineers. Our hopes now hinge on the technologists who are challenged with manufacturing and transporting billions of doses of new, highly complex biotech products—and the public health officials figuring out how best to distribute them to a world that can hardly wait.
Throughout 2020, vaccine producers and their suppliers constructed new factories and otherwise increased their capacity while governments, international agencies, and philanthropies signed billion-dollar contracts, preordering doses by the hundreds of millions. In the United States, the federal initiative known as Operation Warp Speed deployed a budget of more than US $12 billion to develop, test, and mass-produce new vaccines along with the vials, syringes, and other materials needed to deliver them to an anxious populace.
Moncef Slaoui, the initiative’s chief scientist, told IEEE Spectrum in October that the U.S. government had already begun stockpiling two vaccines (from Pfizer and Moderna), and that commercial-scale production was beginning on two others. “So if and when they are approved” by regulators at the U.S. Food and Drug Administration (FDA), he said, “those can be used in the [U.S.] population immediately.”
Creation and deployment of a new vaccine against a novel disease normally takes at least a decade. The audacious goal of Operation Warp Speed and like-minded efforts in other nations is to complete this feat in less than two years. The pace is every bit as intense as the space race of the 1960s, but the stakes are far higher.
There are plenty of reasons for skepticism. “When was the last time anybody made a billion of anything safely and reliably?” asks Arthur Caplan, a bioethics professor at NYU Grossman School of Medicine. “Never,” he says. “Plants go offline, crap breaks, you can’t find a part.” Caplan argues that we should expect snafus: “There’s a ton of things that can go wrong just on manufacturing.”
But also consider this: In 2019, brewers in the United States used applied microbiology to ferment, filter, fill, package, and distribute nearly 50 billion bottles and cans of beer—all in copacetic single-dose units, most of it refrigerated.
Will the university, industry, and government teams grappling with the vaccine challenge be able to bring together the interrelated technical systems that must work in concert—including massive bioreactors and purification lines, acres of fast-fill vials, and thousands of planeloads of ultracold shipping containers? Can humanity really pull this off?
Somewhat surprisingly, the answer so far appears to be: Yes, we can.
Not everything willgo smoothly. Paul Offit, a member of the COVID-19 vaccine working group at the U.S. National Institutes of Health, sat down in June to talk with the editor of the Journal of the American Medical Association about the steep road ahead. “The hardest thing about making a vaccine is mass-producing it,” Offit said. “You have to have the right buffering agent, the right stabilizing agent. You have to have the right vial. You have to do real-time stability studies to make sure that when the vaccine leaves the manufacturing plant, that the time it takes to get from the tarmac to the person’s arm does not cause any problems. Because, remember, when you’re shipping vaccines, they’re going to be exposed to high temperatures and low temperatures, and you have to make sure that you have a stable product.”
Take, for example, the RNA-based vaccine that Pfizer and its German partner BioNTech developed—the first to be approved by the FDA. This kind of vaccine contains slightly altered pieces of the virus’s genetic material (RNA) encased in nanometer-size fatty blobs, which fuse with human cells and cause them to produce the SARS-CoV-2 spike protein, thus triggering an immune response in the body. None of the vaccine experts interviewed for this article had dared to hope that any COVID-19 vaccine—let alone an RNA-based vaccine, a type that’s never before been commercialized—would achieve a 95 percent efficacy rate.
But that stellar effectiveness can wink out if the vaccine gets too warm for too long. As Offit emphasized, temperature affects all vaccines; most (including AstroZeneca’s) must remain between 2 °C and 8 °C to retain potency. RNA vaccines, however, are especially unstable.
At its assembly plants in Kalamazoo, Mich., and Puurs, Belgium, Pfizer has warehouses full of ultracold freezers to store its vaccine at –70 °C. Workers pack the frozen vials into custom-built containers that each hold about 1,000 of them, along with a layer of dry-ice pellets. Also in the box is a GPS-enabled thermal sensor that transmits the temperature and location of the package as it moves via trucks and planes to distribution centers throughout the world.
Distributors are rapidly scaling up too. UPS has said that it’s building two warehouses full of deep freezers—one in Louisville, Ky., and another in the Netherlands—that are capable of storing enough COVID-19 vaccines to inoculate millions of people. FedEx, which routinely delivers about 500,000 dry-ice-packed shipments a month, is doing the same in Memphis, Indianapolis, and Paris.
Rich Gottwald, president of the Compressed Gas Association, says that a nationwide shortage of carbon dioxide last spring spurred CO2 producers to work closely with vaccine makers, ensuring that dry ice will be there when and where they need it. “There may be some challenges in getting the vaccine distributed, but dry ice is not one of those challenges,” he says.
Most of these trips from factory to pharmacy or clinic should take no more than three days, and Pfizer’s vaccine stays fresh for up to 10 days in its container when unopened. Once thawed, the liquids must be kept in pharmacy-grade refrigerators and used within five days. Moderna claims its RNA vaccine can be transported and stored in deep freezers at –20 °C for up to six months and then refrigerated at distribution points for up to 30 days.
Unfortunately, only technologically advanced nations will be able to manage all these logistical complexities. In September, the shipping company DHL analyzed the transport challenges posed by a global rollout of COVID-19 vaccines. Its report concluded that mass distribution of vaccines requiring dry ice for storage will be feasible in only about two dozen countries, accounting for 2.5 billion people. All of Africa, most of South America, and much of Asia would struggle to put such a vaccine to widespread use.
In contrast, DHL estimates, around 60 countries would find it quite possible to inoculate their combined 5 billion residents with vaccines like AstraZeneca’s, which can be stored and transported at refrigerator temperatures of 2 °C to 8 °C (a typical temperature in pharmaceutical supply chains). Both ease of transport and substantially lower manufacturing costs favor more traditional vaccines, such as those that use harmless viruses to trigger an immune response. AstraZeneca’s vaccine, for example, is expected to sell for about a third the cost of the RNA vaccines.
In the hope of making coronavirus vaccines available to even the poorest nations, the World Health Organization, the Coalition for Epidemic Preparedness Innovations, and Gavi, the Vaccine Alliance have joined together to form the COVAX initiative. The coalition has been raising money to secure 2 billion vaccine doses through 2021 for the 90-plus low- and middle-income countries expected to participate, many of which can’t afford to buy or make vaccines on their own. As of mid-November, COVAX reported about US $2 billion in pledged donations, but it said at least $5 billion more is needed to achieve its goal.
These front-runners are just the opening salvo in what will be a protracted battle against SARS-CoV-2. Reinforcements, in the form of other vaccine options, should arrive in 2021 and will be crucial in bringing this pandemic to an end.
“No one manufacturer is going to be able to scale up and make enough doses for 7 billion people,” says Leonard Friedland, director of scientific affairs and public health at GSK Vaccines. “So I hope they all work.”
Pfizer said in July that it was aiming to produce 100 million doses of its product by the end of 2020, but by November it had halved that estimate. The hardest part for Pfizer has been mixing the synthetic pieces of RNA with fatty acids and cholesterol to form delivery particles of just the right size, says Slaoui of Operation Warp Speed. “These mixing operations are very complex,” he says.
And there is likely to be a shortage of cholesterol needed for the lipid nanoparticles, warns Jake Becraft, CEO of Strand Therapeutics, a biotech company in Massachusetts that is developing RNA vaccines of its own. “The simple fact is that those supply chains were nowhere near ready for the demand of billions of vaccines,” Becraft says. Some capacity can be redirected to support COVID-19 vaccine production, he says, “but it will also come at the cost of a lot of drugs in the pipeline for diseases like cystic fibrosis and cancer” that require the same ingredients.
Nevertheless, Pfizer has projected that it will produce up to 1.3 billion doses of COVID-19 vaccine by the end of 2021. Because each person’s inoculation requires two doses spaced two or three weeks apart, that should be enough to protect roughly 650 million people. The U.S. government has prepurchased 100 million of those doses, with an option to buy 500 million more.
As of press time, Moderna was hoping that its vaccine would be ready for broad release to the public in late December, assuming that all went smoothly with its licensing application to the FDA. The company signed up a manufacturing partner, Lonza Group, which is scaling up global manufacturing to be able to deliver 100 million doses a year from its site in Portsmouth, N.H., and another 300 million doses a year from a larger facility in Visp, Switzerland.
Meanwhile, in China, the companies Sinopharm and Sinovac have late-stage trials underway on three vaccines that contain intact coronavirus, which is harvested from live cell cultures and then chemically treated so that it cannot reproduce inside a person. This technology, used to make the annual flu vaccine and many others, has a long track record of success. And China has lots of manufacturing capacity for making inactivated-virus vaccines, notes John Moore, a professor of immunology at Weill Cornell Medical School in New York. Sinopharm is reportedly gearing up to produce 1 billion doses of its vaccine in 2021, if the product succeeds in trials.
But drugmakers elsewhere have largely steered clear of vaccines made from live cells infected with the SARS-CoV-2 virus, which pose obvious dangers to workers. The need for “biosafety level 3” facilities designed and certified to handle such biohazards makes such products harder to scale up, according to Kate Bingham, who chairs the U.K. government’s Vaccines Taskforce.
Of the remaining five vaccines in final-stage trials, four (including the AstraZeneca vaccine) are made by inserting a key gene from the coronavirus into a largely harmless human or chimpanzee adenovirus. After injection, these viral vector vaccines produce the important SARS-CoV-2 protein fragment inside the body, triggering an immune reaction.
The tricky part is harvesting enough of the engineered adenoviruses from the cell cultures in which they are grown. “The biggest issue as we scale up has been optimizing the infection step,” Slaoui says. Stirring 2,000 liters of living cells well enough to let the virus infect most of them—but gently enough so as not to rupture many of them—has proven difficult.
A similar scale-up challenge comes up in the production of the final kind of vaccine, one made by Novavax in Gaithersburg, Md. The company makes its protein vaccine in a factory in Morrisville, N.C., by growing huge batches of armyworm moth cells, which it has genetically engineered to churn out copies of a subunit of the coronavirus’s spike protein. After breaking up the cells and purifying the slurry, workers mix the desired protein with harmless microscopic particles that will carry the virus fragment into the body to trigger an immune response.
Here, Slaoui says, the big challenge is to bust up the cells in a way that doesn’t completely overwhelm the purification process with unwanted moth proteins. The company has a clinical trial underway in the United Kingdom, but in late November it delayed planned trials in the United States and Mexico because production was not scaling up as quickly as anticipated.
Nevertheless, Novavax has promised the U.S. government 100 million doses as they come off its production lines, and the company claims it has the capacity at a plant it bought in the Czech Republic to make a billion more doses in 2021.
If several vaccines gain approval and begin ramping up production in parallel, could there be what engineers call a “common mode” failure? The vaccines may vary, for example, but so far they’re all packaged the same way—in 5-milliliter vials made of a special kind of glass—and then injected into the arm via syringe.
Vaccines are so potent that each vial typically holds enough for five doses. Moderna claims its RNA vaccine is stronger still, so doctors can get 10 doses from every vial. On the one hand, that means that a 1,000-vial container of Moderna vaccine could give 10,000 people one of the two doses they will need. On the other hand, every vial that breaks wastes that many more doses.
The problem with frozen vaccines isn’t that ultracold temperatures make vials brittle, says Robert Schaut, the scientific director of pharmaceutical technologies at the glass-making company Corning. “You’re already below its glass-transition temperature, unlike a plastic or other material. So glass is exactly as strong at –70 °C as it is at room temperature,” he points out. “But when you cool vaccine down to those temperatures, the liquid expands and puts a lot of stress on the glass.”
Two years ago, Corning came out with a stronger, aluminosilicate glass that can be prestressed during vial manufacture by replacing sodium atoms in the materials with potassium atoms. That switch introduces hundreds of megapascals of compressive stress into the material—plenty enough to resist breakage during freezing or transport, Schaut says. He claims that the stronger glass vials also eliminate flaking and dramatically reduce tiny particles dislodged during the filling process, which in the past has led to recalls of conventional glass vials.
More useful still, the new vials are slippery. At the fill-finish stage of vaccine production, when big batches of vials are jostling along through the machinery, the slick coating on the vials lets them glide past each other more easily. Reducing jams on manufacturing lines adds 20 to 50 percent to the throughput, Schaut says, and once lines are moving smoothly, operators can double their speed.
Since the first quarter of 2020, Corning has been shipping millions of vials a month to its Operation Warp Speed partners from its plants outside Corning, N.Y. The company used part of its $204 million government contract to speed construction of a new factory in North Carolina, set to come online next year. Schaut says Corning should now be able to churn out 164 million vials a year—enough to ship at least 820 million doses of vaccine.
“We set the objectiveto have enough vaccine to immunize the U.S. population by the first half of 2021,” said Slaoui of Operation Warp Speed, in October. “And that definitely will be the case. We will have 600 million to 700 million doses or more by May or June 2021.”
Thanks to unprecedented government investments, an impressively coordinated scramble by several industries, and some fortuitous technological advances, Slaoui’s boast seems credible. Since April, Stacy Springs and Donovan Guttieres at M.I.T.’s Center for Biomedical Innovation have been collecting data about each step of the supply, production, and distribution chains for COVID-19 vaccines. They have built models to investigate dependencies and identify critical points where shortages could interrupt production.
So far, Springs says, they have seen companies and agencies cooperating to spot problems and fix them: “A lot of the manufacturers are already moving to dual sourcing of materials and putting in other safety nets, so that they’re not going to be in a position where they don’t have what they need.” Although governments have been competing with one another to some extent to preorder vaccine for their own people, “there’s a lot of goodwill and sharing going on within the industry,” she says.
It is indeed encouraging to learn that the immense efforts being mounted now to vaccinate the world against COVID-19 are being undertaken in a cooperative spirit. Perhaps, after a year of divisiveness and social isolation, the realization is dawning that we’re all in this together.
They look like regular earbuds, but these headphones don’t play music, or produce any kind of sound. Instead, they produce electrical fields designed to treat disease.
By delivering electrical pulses to a nerve in the outer ear, the device hacks into neural circuits in the brain in a way that could regulate inflammation and treat rheumatoid arthritis.
That’s the hope, anyway, of researchers at the start-up Nēsos, which launched out of stealth mode today. “We’re still at the early stages of development,” says Konstantinos Alataris, co-founder and CEO of the company. “We’re developing this as a prescription product and testing it in clinical trials.”
And arthritis is just the first application that the startup is pursuing. If Nēsos has found an effective way to hack into the brain, the earbuds could help with a range of neurological and psychiatric diseases.
Edmund Optics’ asphere experts Amy Frantz and Oleg Leonov, and moderator Lars Sandström, Precision Optics Senior Business Line Manager, present the benefits of using aspheres in optical system design and what factors need be taken into account during the design process. These key manufacturability considerations will significantly reduce asphere lead time and cost if considered early enough in the design process.
At the conclusion of this webinar, participants will have a strong understanding around:
Benefits of using aspheres in optics system design
In 2007, U.S. vice president Dick Cheney ordered his doctors to disable all wireless signals to and from his Internet-connected pacemaker. Cheney later said that the decision was motivated by his desire to prevent terrorists from being able to hack his pacemaker and use it to lethally shock his heart. Cheney’s command to his doctors might seem to some to be overly cautious, but wirelessly connected medical devices have a history of exploitable vulnerabilities. At a series of conferences in 2011 and 2012, for example, New Zealand hacker Barnaby Jack showed that connected medical devices could be remotely attacked. Jack used a high-gain antenna to capture the unencrypted electromagnetic signals transmitted by an insulin pump on a mannequin 90 meters away. He then used those signals to hack into the pump and adjust the level of insulin the pump delivered. He also hacked a pacemaker and made it deliver deadly electric shocks.
Medical devices are only the tip of the iceberg when it comes to the wireless devices people are putting in or on their bodies. The list includes wireless earbuds, smartwatches, and virtual-reality headsets. Technologies still in development, such as smart contact lenses that display information and digital pills that transmit sensor data after being swallowed, will also be at risk.
All of these devices need to transmit data securely at low power and over a short range. That’s why researchers have started to think about them as individual components of a single human-size wireless network, referred to as a body-area network. The term “Internet of Bodies” (IoB) is also coming into use, taking a cue from the Internet of Things.
At the moment, IoB devices use established wireless technologies, mainly Bluetooth, to communicate. While these technologies are low power, well understood, and easy to implement, they were never designed for IoB networks. One of Bluetooth’s defining features is the ability for two devices to easily find and connect to one another from meters away. That feature is precisely what allows a hypothetical attacker to snoop on or attack the devices on someone’s body. Wireless technologies have also been designed to travel through air or vacuum, not through the medium of the human body, and therefore they are less efficient than a method of communicating designed to do so from scratch.
Through our research at Purdue University, we have developed a new method of communication that will keep medical devices, wearables, and any other devices on or near the body more secure than they are using low-power wireless signals to communicate with one another. The system capitalizes on the human body’s innate ability to conduct tiny, harmless electrical signals to turn the entire body into a wired communication channel. By turning the body into the network, we will make IoB devices more secure.
Sensitive personal data like medical information should always be encrypted when it’s transmitted, whether wirelessly or in an email or via some other channel. But there are three other especially good reasons to prevent an attacker from gaining access to medical devices locally.
The first is that medical data should be containable. You don’t want a device to be broadcasting information that someone might eavesdrop on. The second reason is that you don’t want the integrity of the device to be compromised. If you have a glucose monitor connected to an insulin pump, for example, you don’t want the pump to release more glucose because the monitor’s data was compromised. Not enough glucose in the blood can cause headaches, weakness, and dizziness, while too much can lead to vision and nerve problems, kidney disease, and strokes. Either situation can eventually lead to death. The third reason is that the device’s information always needs to be available. If an attacker were to jam the signals from an insulin pump or a pacemaker, the device might not even know it needed to respond to a sudden problem in the body.
So if security and privacy are so important, why not use wires? A wire creates a dedicated channel between two devices. Someone can eavesdrop on a wired signal only if they physically tap the wire itself. That’s going to be hard to do if the wire in question is on or inside your body.
Setting aside the benefits of security and privacy, there are some important reasons why you wouldn’t want wires crisscrossing your body. If a wire isn’t properly insulated, the body’s own biochemical processes can corrode the metal in the wire, which could in turn cause heavy-metal poisoning. It’s also a matter of convenience. Imagine needing to repair or replace a pacemaker with wires. Rethreading the wires through the body would be a very delicate task.
Rather than choose between wireless signals, which are easy for eavesdroppers to snoop, and wired signals, which bring risk to the body, why not a third option that combines the best of both? That’s the inspiration behind our work to use the human body as the communication medium for the devices in someone’s body-area network.
We call the method of sending signals directly through the body electro-quasistatic human-body communication. That’s a mouthful, so let’s just think of it as a body channel. The important takeaway is that by exploiting the body’s own conductive properties, we can avoid the pitfalls of both wired and wireless channels.
Metal wires are great conductors of electric charge. It’s a simple matter to transmit data by encoding 1s and 0s as different voltages. You need only define 1s as some voltage, which would cause current to flow through the wire, and 0s as zero voltage, which would mean no current flowing through the wire. By measuring the voltage over time at the other end of the wire, you end up with the original sequence of 1s and 0s. However, given you don’t want metal wires running around or through the body, what can you do instead?
The average adult human is about 60 percent water by weight. And though pure water is a terrible electrical conductor, water filled with conductive particles like electrolytes and salts conducts electricity better. Your body is filled with a watery solution called the interstitial fluid that sits underneath your skin and around the cells of your body. The interstitial fluid is responsible for carrying nutrients from the bloodstream to the body’s cells, and is filled with proteins, salts, sugars, hormones, neurotransmitters, and all sorts of other molecules that help keep the body going. Because interstitial fluid is everywhere in the body, it allows us to establish a circuit among two or more communicating devices sitting pretty much anywhere on the body.
Imagine someone with diabetes who uses an insulin pump and a separate monitor on the abdomen to manage blood glucose levels. Suppose they want their smartwatch, among its many other functions, to display current glucose levels and the operational status of the pump. Traditionally, these devices would have to be connected wirelessly, which would make it theoretically possible for anyone to grab a copy of the user’s personal data. Or worse, potentially attack the pump itself. Today, many medical devices still aren’t encrypted, and even for those that are, encryption is not a guarantee of security.
Here’s how it would work with a body channel instead. The pump, the monitor, and the smartwatch would each be outfitted with a small copper electrode on its back, in direct contact with the skin. Each device also has a second electrode not in contact with the skin that functions as a sort of floating ground, which is a local electrical ground that is not directly connected with Earth’s ground. When the monitor takes a blood glucose measurement, it will need to send that data to both the pump, in case the insulin level needs to be adjusted, and to the smartwatch, so that the individual can see the level. The smartwatch can also store data for long-term monitoring, or encrypt it and send it to the user’s computer, or their doctor’s computer, for remote storage and analysis.
The monitor communicates its glucose measurements by encoding the data into a series of voltage values. Then, it transmits these values by applying a voltage between its two copper electrodes—the one touching the human body, and the one acting as a floating ground.
This applied voltage very slightly changes the potential of the entire body with respect to Earth’s ground. This tiny change in potential between the body and Earth’s ground is just a fraction of the potential difference between the monitor’s two electrodes. But it’s enough to be picked up, as an even smaller fraction after crossing the body, by the devices elsewhere. Because both the pump on the waist as well as the smartwatch on the wrist are on the body, they can detect this change in potential across their own two electrodes—both on-body and floating. The pump and the smartwatch then convert these potential measurements back into data. All without the actual signal ever traveling beyond the skin.
One of the biggest challenges for realizing this method of body communication is in selecting the best wavelengths for the electrical signals. Electrical wavelengths like the ones we’re considering here are much longer than the RF wavelengths for wireless communications.
The reason selecting a frequency is a challenge is that there is a range of frequencies at which the human body itself can become an antenna. An ordinary radio antenna creates a signal when an alternating current causes the electrons in its material to oscillate and create electromagnetic waves. The frequency of the transmitted waves depends on the frequency of the alternating current fed into the antenna. Likewise, an alternating current at certain frequencies applied to the human body will cause the body to radiate a signal. This signal, while weak, is still strong enough to be picked up with the right equipment and from some distance away. And if the body is acting as an antenna, it can also pick up unwanted signals from elsewhere that might interfere with wearables’ and implants’ ability to talk with one another.
For the same reason you don’t want to use technologies like Bluetooth, you want to keep electrical signals confined to the body and not accidentally radiating from or to it. So you have to avoid electrical frequencies at which the human body becomes an antenna, which are in the range of 10 to 100 megahertz. Above that are the wireless bands, and we’ve already mentioned the problems there. The upshot is that you need to use frequencies in the range of 0.1 to 10 MHz, in which signals will stay confined to the body.
Earlier attempts to use the human body to communicate have usually shied away from these lower frequencies because the body is typically high loss at low frequencies. In other words, signals at these lower frequencies require more power to guarantee that a signal will make it to its destination. That means a signal from a glucose monitor on the abdomen might not make it to a smartwatch on the wrist before it’s unreadable, without a significant boost in power. These previous efforts were high loss because they focused on sending direct electrical signals, rather than information encoded in potential changes. We’ve found that the parasitic capacitance between a device and the body is key to creating a working channel.
Capacitance refers to the ability of an object to store electrical charge. Parasitic capacitance is unwanted capacitance that occurs unintentionally between any two objects. For example, two charged areas in close proximity on a circuit board, or between a person’s hand and their phone. Typically, parasitic capacitance is a nuisance, although it also enables certain applications like touch screens.
Astute readers may have picked up that we haven’t mentioned one key aspect of circuits before now: A circuit needs to be a closed loop for electrical communication to be possible. Up until now, we’ve restricted our discussion to the forward path, meaning the part of the circuit from the transmitting electrode to the receiving electrode. But we need a path back. We have one thanks to parasitic capacitance between the floating ground electrodes on the devices and Earth’s ground.
Here’s how to picture the circuit we’re using. First, imagine two circuit loops. The first loop begins with the transmitting device, at the electrode touching the skin. The circuit then goes through the body, down through the feet to the actual ground, and then back up through the air to the other (floating) electrode on the transmitting device. We should note here that this is not a loop through which direct current can flow. But because parasitic capacitances exist between any two objects, such as your feet and your shoes, and your shoes and the ground, a small alternating current can exist.
The second loop, in a similar fashion, begins with the receiving device, at its electrode that is touching the skin. It then goes through the body—both loops share this segment—to the ground, and back through the air to the floating-ground electrode on the receiving device.
The key here is to understand that the circuit loops are important not because we have to push a current through them necessarily, but because we need a closed path of capacitors. In a circuit, if the voltage changes across one capacitor—for example, the two electrodes of the transmitting device—it creates a slight alternating current in the loop. The other capacitors, meaning both the body and the air, “see” this current and, because of their impedances, or resistances to the current, their voltages change as well.
Remember that the circuit loop with the transmitting device and the one with the receiving device share the body as a segment of their respective loops. Because they share that segment, the receiving device also responds to the slight change in the body’s voltage. The two electrodes making up the receiving device’s capacitor detect the body’s changing voltage and allow that measurement to be decoded as meaningful information.
We have found that we want any IoB device’s capacitor to have high capacitance. If this is the case, relatively high voltages created by the transmitting device will result in extremely low currents in the body itself. Obviously, this makes sense from a safety perspective: We don’t want to run high current through the body, after all. But it also makes the communications channel low loss. That’s because a high-impedance capacitor will be particularly sensitive to minor changes in current. The upshot is that we can keep the current low (and safe) and still get clear voltage measurements at the receiving device. We’ve found that our technique results in a reduction in loss of two orders of magnitude compared with previous attempts to create a wireless channel in the body, which relied on sending an electrical signal via current directly through the body.
Our method for turning the human body into a communications channel shifts the distance at which signals can be intercepted from the 5- to 10-meter range of Bluetooth and similar signals to below 15 centimeters. In other words, we’ve reduced the distance over which an attacker can both intercept and interfere with signals by two orders of magnitude. With our method, an attacker would need to be so close to the target that there’s no way to hide.
Not only does our method offer more privacy and security for anyone with a medical implant or device, but as a bonus, the communications are far more energy efficient as well. Because we’ve developed a system that is low loss at low frequencies, we can send information between devices using far less power. Our method requires less than 10 picojoules per transferred bit. For reference, that’s about 0.01 percent of the energy required by Bluetooth. Using 256-bit encryption, it drew 415 nanowatts of power to transmit 1 kilobit per second, which is more than three orders of magnitude below Bluetooth (which draws between 1 and 10 milliwatts).
Medical devices like pacemakers and insulin pumps have been around for decades. Bluetooth earbuds and smartwatches may be newer, but neither life-saving medical equipment nor consumer tech is leaving our bodies any time soon. It only makes sense to make both categories of devices as secure as possible. Data is always most vulnerable to a malicious attack when it is moving from one point to another, and our IoB communication technique can finally close the loop on keeping personal data from leaving your body.
This article appears in the December 2020 print issue as “To Safeguard Sensitive Data, Turn Flesh and Tissue Into a Secure Wireless Channel.”
About the Author
Shreyas Sen is an associate professor of electrical and computer engineering at Purdue University. He is a Senior Member of the IEEE. Shovan Maity and Debayan Das are graduate students of Sen at Purdue University.
Aspheres as key optical components are true “enablers” in the field of optics and photonics, especially for applications which require light weight and small size. The whitepaper gives an overview of important asphere specifications and the impact they can have on optical performance.
Learn about Aspheres and their specifications and understand how to best use them to optimize performance of your optical system.
Given the potential consequences of worker fatigue, scientists have been exploring wearable devices for monitoring workers’ alertness, which correlates with physiological parameters such as heart rate, breathing rate, sweating, and muscle contraction. In a recent study published November 6 in IEEE Sensors Journal, a group of Italian researchers describe a new wearable design that measures the frequency of the user’s breathing—which they argue is a proxy for fatigue. Breathing frequency is also used to identify stressing conditions such as excessive cold, heat, hypoxia, pain, and discomfort.
“This topic is very important since everyday thousands of work-related accidents occur throughout the world, affecting all sectors of the economy,” says Daniela Lo Presti, a PhD student at Università Campus Bio-Medico di Roma, in Rome, Italy, who was involved in the study. “We believe that monitoring workers’ physiological state during [work]… may be crucial to prevent work-related accidents and improve the workers’ quality performances and safety.”
The sensor system that her team designed involves two elastic bands that are worn just below the chest (thorax) and around the abdomen. Each band is flexible, made of a soft silicon matrix and fiber optic technology that conforms well to the user’s chest as he or she breathes.
“These sensors work as optical strain gauges. When the subject inhales, the diaphragm contracts and the stomach inflates, so the flexible sensor that is positioned on the chest is strained,” explains Lo Presti. “Conversely, during the exhalation, the diaphragm expands, the stomach depresses, and the sensor is compressed.”
The sensors were tested on 10 volunteers while they did a variety of movements and activities, ranging from sitting and standing to lateral arm movements and lifting objects from the ground. The results suggest that the flexible sensors are adept at estimating respiratory frequency, providing similar measurements to a flow meter (a standard machine for measuring respiration). The researchers also found that their sensor could be strained by up to 2.5% of its initial length.
Lo Presti says this design has several strengths, including the conformation of the sensor to the user’s body. The silicon matrix is dumbbell shaped, allowing for better adhesion of the sensing component to the band, she says.
However, the sensing system must be plugged into a bulky instrument for processing the fiber optical signals (called an optical interrogator). Lo Presti says other research teams are currently working on making these devices smaller and cheaper. “Once high-performant, smaller interrogators are available, we will translate our technology to a more compact wearable system easily usable in a real working scenario.”
Steven Cherry Hi, this is Steven Cherry for Radio Spectrum.
You know what a hospital operating room looks like—at least from TV shows. There’s the surgeon, of course, maybe a surgical resident, nurses, a scrub tech, the anesthesiologist, maybe a few aides; some students, if it’s a teaching hospital.
But an actual modern hospital operating room probably has someone you never see on television: a medical device company representative. The device might be a special saw or probe or other tool for the surgeon to use; it might be a device being implanted, such as an artificial hip, knee, or mandible; a pacemaker—even, lately, internal braces to stabilize someone’s spine.
The toolkits for some of these devices might include dozens of wrenches and screws. The surgeon may be using the device and the kit for the first time. The medical device company representative quite probably knows more about the device and its insertion than anyone on the surgical team.
Obviously, in the time of the coronavirus, it’s a plus to have as few people in the OR as possible. But even in non-Covid times, it’s inefficient to fly these company reps around the country to observe and advise an operation that might only take an hour. And so, in a handful of ORs, you’ll see something else—one or more cameras, mounted strategically, and a flat-panel screen on a console, connected to a remote console. The medical device rep—or a consulting surgeon—can be a thousand kilometers away, controlling the cameras, looking at an MRI scan, and making notations on their tablet that can be seen on the one in the operating room.
It’s telemedicine for the OR, and it’s the brainchild of my guest today.
Daniel Hawkins is a serial inventor with well over 100 patents to his name and a serial entrepreneur with several startups to his résumé. His latest, is the one whose system we’re taking about today, Avail Medsystems. He joins us by Zoom.
Daniel, welcome to the podcast.
Daniel Hawkins Thanks for the opportunity, Steven. Happy to be here.
Steven Cherry Daniel, I didn’t know anything about these medical device reps. I gather they’re often part of the marketing or customer support teams at their companies, but they undergo some real surgical training before they start advising doctors.
Daniel Hawkins They do, in fact, Steven, typically the training regimens are several weeks, if not several months long, and then after they complete those training regimens, they’re required to travel with somebody very experienced in the operating rooms and they get what was initially a didactic training in the classroom setting or possibly even cadaveric lab setting, then converts to real-world settings in operating rooms where their teacher, if you will, has been on the job for an extended time period. And does a teacher mentor kind of a training session on an ongoing basis for several weeks, if not a few months, with a representative before they are turned loose.
Steven Cherry This isn’t just Zoom for operating rooms. The cameras, for example, aren’t like the webcam in my computer.
Daniel Hawkins No, they’re not. These are, in fact, 30x optical-zoom cameras. I can confidently say there’s not a camera on the planet that we haven’t tried! And have ultimately chosen a pair of cameras that have incredible clarity, color-balancing, and appropriate low-level-light image-capture capability. Because in operating rooms you need all of those things. The remote individual being a sales rep or a trained physician in an open surgery needs to have crystal clear images of the tissue that they are operating on. And color and color balancing, white-balancing, and tissue-plane identification are really relying on high-end optical clarity.
Steven Cherry The cameras were just one of the engineering challenges you faced.
Daniel Hawkins We are requiring high-definition audio and a high-definition video at a local source, meaning the operating room. We’re transferring that via a HIPPA-compliant, fully-encrypted Internet connection, bouncing off the cloud and then down to a remote participant, being the industry representative or possibly an advising surgeon could be across town and across the country or across the globe. And our system is designed to have latency of less than half a second. Now, of course, we’re dependent on the quality of the local and the remote Internet connections. But before we install a system, we care for the local issues with provisioning of the network in the hospital.
Steven Cherry Another challenge was the business model. There’s a hundred thousand dollars worth of equipment here, but your solution doesn’t involve customers shelling out that money.
Daniel Hawkins That’s right, I’ve been, Steven, twenty-six years in the medical device business and one of the first capital equipment businesses I was involved in with within health care is actually The Da Vinci surgical robot produced by Intuitive Surgical. That’s a two-million-dollar robot. Be it two million dollars, two hundred thousand dollars, or even two thousand dollars requires extensive approvals inside of hospitals to go through a capital acquisition process and model. And that really would delay our commercialization if we required that to get our systems placed. We decided instead to pursue a very aggressive model, inasmuch as we’re not charging at all for that hardware. We’re not charging a capital cost, we’re not charging a lease. We’re not even charging for the upkeep and maintenance or technical support. It’s fully free of charge to the hospitals from a capital perspective. What we do instead is market the utilization of the these systems in a fee-for-service based on time.
Steven Cherry In some sense, your customer is also the medical device manufacturer.
Daniel Hawkins Yes, we’re really a two-sided network. The first side, of course, is placing the consoles in hospitals or ambulatory surgery centers where we generate our revenues from the fees paid by the remote participant. And in the vast majority of cases, that is, in fact, the medical device manufacturer, that is the Johnson and Johnson or Medtronic or an Abbott or Boston Scientific. The variety of medical device companies have an aggregate of over 100 000 sales reps and clinical specialists. Those are folks that are somewhat like sales, that they don’t have a sales quota. Their whole job is to support procedures. There’s 110 000 just sales reps and probably something similar in the clinical specialist field force. These people need access to operating rooms every day. They waste an extraordinary amount of time driving between their different customers from one hospital to the next and waiting for a procedure once they arrive at the hospital waiting for the next procedure. The estimates are about 50 percent of their time is wasted in logistics. You can have a significant increase in the efficiency of time spent supporting your customers, those customers being the surgeons who were conducting the operation.
Steven Cherry We think of the remote experience as being inferior, but it seems there are some advantages here. For example, being able to look at scans more easily.
Daniel Hawkins That’s a great way of thinking about it. There are really a number of advantages. In an operating room, when you go as an industry representative to help a surgeon through the specifics of using some type of a device that you’re representing, you have to observe what’s called a sterile field—kind of an imaginary bubble that extends probably six or eight feet around every dimension of the operating table. That means you need to stand back. If you’re standing back, it’s kind of hard to see the operating field itself. And you can’t point to anything unless you use a laser pointer, which is a common tool in many reps bags.
And you also can’t really annotate or draw on a screen—if you kind of imagine there being a screen is displaying part of the procedure, could be from a moving X-ray called an angiogram if it’s an angioplasty placing a stent in the heart, or it could be a screen with a full video image, if it is a minimally invasive surgery procedure; it’s called laparoscopic surgery. And you might want to actually point something out to the surgeon. You can’t really do that with a tool that would allow you to draw and really point something out. Those are two examples of things that we solve with the Avail system. But because of the nature of our cameras and our console, you can actually get a better view of the operator field using our system than you could get if you were physically in the room. Our cameras, one of them is on a boom arm, is positioned over the operating field and you were able to see directly down under the operating field and zoom down and quite literally count the eyelashes on the patient if you wanted to do that. The level of of visual acuity is quite impressive. We also get an ability for somebody remote to draw on the screen, almost like you might see on Monday Night Football.
Steven Cherry So is there an increased interest in your system because of the pandemic, or maybe less so because so much in hospitals is on hold while they deal with that one overriding problem?
Daniel Hawkins That’s a great question. The fundamental issues that we’re solving have existed for forty years. Medical devices, have always been supported, trained, and introduced in person. And that’s a challenge. In fact, somewhere between 25 percent and 100 percent of cases require physical presence from industry. Some procedures like angioplasty, about one in four times, there’s a physical person in the room from a medical device company. For pacemakers, they’re actually not implanted unless there’s somebody in the world because the medical device representative is integral to the procedure. The pandemic shone a spotlight on the issues of access and needing that access. And interest levels, Steven actually went up. The awareness of the need for those people in the room against the restrictions of being able to come into the hospital made it very, very apparent that a remote capability was needed.
Another thing happened that was really interesting. What was otherwise an assumption—that health care needed to be delivered in person—that presumption has been shattered in dozens and dozens and dozens of medical device companies have approached us and we are under contract with several dozen right now.
Steven Cherry Daniel, you have something like one hundred and fifty patents. Your last startup, which I guess you’re still an adviser to, took some medical techniques that were well-known in kidney stone treatment and applied them to arterial plaque. None of this seems like the kind of thing that somebody would come up with if their degrees were from Wharton and Stanford in business and management.
Daniel Hawkins So I have been, in many respects, a medical device junkie for a few decades here, 26 years in total. But really, my interest stems even prior to that. My father was a physician. I grew up around medicine. I also grew up around entrepreneurship. What I really sought was a way to combine the two and didn’t know much about the medical-device industry. But what I did understand is I really thought the tools that surgeons used were pretty interesting.
When I was an undergraduate, I actually attempted to pursue a joint undergrad Wharton and premed degree. And thankfully, the deans of the schools made a different recommendation for me and suggested I take one. I knew I didn’t want to actually be a physician, but I did know that I wanted to be involved in health care. And after business school, I got involved in health care immediately. Really, I didn’t have any patents at all until 20005, I believe it was.
I joined a couple of engineers in an incubator of sorts and our task—we were sponsored by actually venture firms—our task was to create new medical technologies for disease states that were underserved. And they showed me how to invent is probably the best way to describe this, Steven. And after that, I was hooked. It was it just became something where I would observe there’s an issue. And by the nature of that process of incubation, I was the idea guy. I was the one who was trying to find the unmet needs. I would see those. And that means but what I would hear from the engineers I was working with is so many different types of solutions that could be brought to bear in. The beautiful part about that was actually that I was just informed enough to ask the question and just ignorant enough to not stop myself from wanting to pursue it.
Steven Cherry My grandmother was a doctor and, like your father, her office was downstairs in the house I grew up in, but I don’t have scores of medical-related patents, so I knew there was more to this story. You are also an executive at Intuitive Surgical, which makes The Da Vinci surgical robot. In some ways, the Avail system backs away from robot-aided surgery. Why did neither of your recent startups go further down the robotic path?
Daniel Hawkins Really, robotics is a … it’s fascinating … It’s absolutely fascinating. And I think it’s frankly undertapped. There’s a level of expertise that is needed in robotics that I simply don’t have. Having said that, I am an adviser to a brand-new robotic surgery company that is really just incredibly interesting, what they’re working on that—not at liberty, to talk too much about it.
Steven Cherry Getting back to Avail, it would seem helpful for a rural community, say maybe where there’s no surgeon at all, but a doctor or even a nurse practitioner needing to perform a procedure for which they need trained guidance. Is their interest outside of big hospitals in big cities?
Daniel Hawkins There absolutely is. Rural applications, I think, are very relevant. As are military surgery centers. And, you know, there’s many different use cases. And in some ways, I’d encourage you to think of what we’re doing as a telecommunications platform. We are connecting expertise from outside of the procedure room and delivering it to insert the procedure room. And that means really anyone who is an outside expert can clinically contribute to a surgery where somebody might have incrementally less expertise.
It’s also relevant for ambulatory surgery centers where there tend not to be five or six or seven surgeons in a practice group all working the same day at that same location. If there’s a case in a large hospital that a surgeon is working on and they have a question that they think one of their colleagues might be able to help out, they’ll ask a circulating nurse or a technician to call doctor so-and-so. And that physician, if they’re otherwise available, might put on a mask and a pair of gloves and come in and have a look. And they might consult for five minutes or 15 minutes. That’s incredibly valuable and it happens all the time.
Steven Cherry I can imagine the expertise flipping around. This seems like a good tool for observing an operation, if you’re a student at a teaching hospital. Better than being maybe dozens of feet away in the theater.
Daniel Hawkins Absolutely true. In fact, we’re working with a couple of medical universities where they’re actually interested in revamping their curriculum to solve exactly that problem. The issue being that there might be a dozen and a half or two dozen surgeon trainees and they’re circulating around an operating rooms trying to observe what they can. But as a practical matter, it really can only have two maybe at most three trainee surgeons, if you will, in an operating room at any given point in time to observe. Past that it becomes difficult to see and didactically a lot more challenging.
What about outside of medicine? I can imagine a complex engine repair on an oil rig in the Arctic, for example.
Daniel Hawkins Most certainly our technology is not really dependent on the content of what it’s doing. The capability is really universal for anything that involves audio and video. It has been proposed for that type of a remote repair setting that you just described. It’s actually been proposed to be used in hospitals in a similar fashion where the repair of an MRI machine would be consulted by the repairing … the manufacturer, if you will, would consult the biomedical engineer in a facility who’s pointed the cameras at the MRI machine and they can be walked through the steps. You know, for the remote that you just described out in the Arctic, one of the interesting use cases that we’re actively exploring is a military application where one of our units might be on a Marine vessel. As long as they’re able to get a satellite Internet connection. We’re talking about the military so that should not be an issue.
Steven Cherry Well, Daniel, that’s a pretty creative solution to a problem I think most of us didn’t even know existed. I’m sure hospitals and medical device reps are grateful for it. And I’m grateful for your joining us today.
Daniel Hawkins Thanks very much.
Steven Cherry We’ve been speaking with Daniel Hawkins, founder of Avail Medsystems, a startup that’s moving telemedicine from the doctor’s office to the hospital operating room.
Radio Spectrum is brought to you by IEEE Spectrum, the member magazine of the Institute of Electrical and Electronic Engineers, a professional organization dedicated to advancing technology for the benefit of humanity.
And we’re grateful to benefit from open-source—our music is by Chad Crouch and our editing tool is Audacity. This interview was recorded November 2, 2020. Radio Spectrum can be subscribed to on the Spectrum website, Spotify, Apple Podcast, Stitcher, or wherever you get your podcasts. We welcome your feedback on the web or in social media.
The first time Karl Deisseroth used light to control brain cells in a dish, people had a lot of questions, three in particular. Can the technique be used in living animals? Can it target different cell types? Can it work without implanting a light source into the brain?
In the years since that initial groundbreaking 2004 experiment, Deisseroth’s team and others found the answers to the first two questions: yes and yes. This month they answered the third question with another yes, successfully introducing an implant-free version of the technique. It is the first demonstration that optogenetics—which uses a combination of light and genetic engineering to control brain cells—can accurately switch the cells on and off without surgery.
“This is kind of a nice bookend to 16 years of research,” says Deisseroth, a neuroscientist and bioengineer at Stanford University. “It took years and years for us to sort out how to make it work.” The result is described this month in the journal Nature Biotechnology.
Scientists have created a new sensor that can be integrated within dental implants to passively monitor bone growth, bypassing the need for multiple x-rays of the jaw. The design is described in study published September 25 in IEEE Sensors Journal.
Currently, x-rays are used to monitor jaw health following a dental implant. Dental x-rays typically involve low doses of radiation, but people with dental implants may require more frequent x-rays to monitor their bone health following surgery. And, as professor Alireza Hassanzadeh of Shahid Beheshti University, Tehran, notes, “Too many X-rays is not good for human health.”
To reduce this need for x-rays, Hassanzadeh and two graduate students at Shahid Beheshti University designed a new sensor that can be integrated within dental implants. It passively measures changes in the surrounding electrical field (capacitance) to monitor bone growth. Two designs, for short- and long-term monitoring, were created.
The sensors are made of titanium and poly-ether-ether-ketone, and are integrated directly into a dental implant using microfabrication methods. The designs do not require any battery, and passively monitor changes in capacitance once the dental implant is in place.
“When the bone is forming around the sensor, the capacitance of the sensor changes,” explains Hassanzadeh. This indicates how the surrounding bone growth changes over time. The changes in capacitance, and thus bone growth, are then conveyed to a reader device that transfers the measurements into a data logger.
In their study, the researchers tested the sensors in the femur and jaw bone of a cow. “The results reveal that the amount of bone around the implant has a direct effect on the capacitance value of the sensor,” says Hassanzadeh.
He says that the sensor still needs to be optimized for size and different implant shapes, and clinical experiments will need to be completed with different kinds of dental implant patients. “We plan to commercialize the device after some clinical tests and approval from FDA and authorities,” says Hassanzadeh.
New circuits can get printed directly on human skin to help monitor vital signs, a new study finds.
Wearable electronics are growing increasingly more comfortable and more powerful. A next step for such devices might include electronics printed directly onto the skin to better monitor and interface with the human body.
Scientists wanted a way to sinter—that is, use heat to fuse—metal nanoparticles to fabricate circuits directly on skin, fabric or paper. However, sintering usually requires heat levels far too high for human skin. Other techniques for fusing metal nanoparticles into circuits, such as lasers, microwaves, chemicals or high pressure, are similarly dangerous for skin.
In the new study, researchers developed a way to sinter nanoparticles of silver at room temperature. The key behind this advance is a so-called a sintering aid layer, consisting of a biodegradable polymer paste and additives such as titanium dioxide or calcium carbonate.
Positive electrical charges in the sintering aid layer neutralized the negative electrical charges the silver nanoparticles could accumulate from other compounds in their ink. This meant it took less energy for the silver nanoparticles printed on top of the sintering aid layer to come together, says study senior author Huanyu Cheng, a mechanical engineer at Pennsylvania State University.
The sintering aid layer also created a smooth base for circuits printed on top of it. This in turn improved the performance of these circuits in the face of bending, folding, twisting and wrinkling.
In experiments, the scientists placed the silver nanoparticle circuit designs and the sintering aid layer onto a wooden stamp, which they pressed onto the back of a human hand. They next used a hair dryer set to cool to evaporate the solvent in the ink. A hot shower could easily remove these circuits without damaging the underlying skin.
After the circuits sintered, they could help the researchers measure body temperature, skin moisture, blood oxygen, heart rate, respiration rate, blood pressure and bodily electrical signals such as electrocardiogram (ECG or EKG) readings. The data from these sensors were comparable to or better than those measured using conventional commercial sensors that were simply stuck onto the skin, Cheng says.
The scientists also used this new technique to fabricate flexible circuitry on a paper card, to which they added a commercial off-the-shelf chip to enable wireless connectivity. They attached this flexible paper-based circuit board to the inside of a shirt sleeve and showed it could gather and transmit data from sensors printed on the skin.
“With the use of a novel sintering aid layer, our method allows metal nanoparticles to be sintered at low or even room temperatures, as compared to several hundreds of degrees Celsius in alternative approaches,” Cheng says. “With enhanced signal quality and improved performance over their commercial counterparts, these skin-printed sensors with other expanded modules provide a repertoire of wearable electronics for health monitoring.”
The scientists are now interested in applying these sensors for diagnostic and treatment applications “for cardiopulmonary diseases, including COVID-19, pneumonia, and fibrotic lung diseases,” Cheng says. “This sensing technology can also be used to track and monitor marine mammals.”
In his “Plenty of Room at the Bottom” lectureat Caltech in 1959, physicist Richard Feynman urged his audience to make the microscope ever more powerful so that biologists could explore the “staggeringly small world” beyond. It would be a lot easier to answer fundamental biological questions if we could “just look at the thing,” he said.
A few years later, in the science fiction movie Fantastic Voyage, a submarine crew shrinks to microscopic size and goes on a mission through the human body to repair brain damage. The 1966 movie trailer says the film “drops the bottom out of the world you know and understand,” and sends viewers “where no man or camera has gone before.”
Now, scientists have combined the visions of the mid-century physicist and filmmakers in one groovy virtual reality experience. In a paper published last week in Nature Medicine, researchers described new software that enables scientists to enter inside and explore a cell or other biological structures using a virtual reality (VR) headset.
It can sound like a soft buzzing in one’s ears. Or a sudden hissing. Or a loud roaring. Tinnitus, the sensation of hearing phantom sounds, ranges from annoying to debilitating, and it affects an estimated 10 to 15 percent of the population. Unfortunately, finding relief from these symptoms can be tough.
Doctors and patients may find themselves attempting many treatments for tinnitus, including sound machines to mask the phantom noise, medications to treat underlying anxiety or depression, and investigational brain implants or vagus nerve stimulation. In the United States, there are currently no clinically approved drugs or devices to treat tinnitus.
Now, in a paper published today in the journal Science Translational Medicine, researchers at Dublin-based biotech Neuromod Devices, along with academic collaborators, present positive results from a year-long, randomized clinical trial of a device that pairs sound with gentle electrical tongue stimulation to treat tinnitus. In a group of 326 adults, 12 weeks of treatment with the device significantly reduced tinnitus symptom severity for up to 12 months after treatment.
Covid-19 spreads via droplets expelled from an infected person’s lungs, so determining how the release of moisture is affected by different masks is an important step towards better protective gear. Now, using a new technique in 3D printing, University of Cambridge researchers have created tiny, freestanding, conducting fibers they claim can detect respiratory moisture more effectively than anything currently on the market.
The researchers demonstrated the fiber sensors by testing the amount of breath moisture that leaks through face coverings. They attached their fiber array to the outside of the mask, wired it to a computer, and found that it outperformed conventional planer chip-based commercial sensors, particularly when monitoring rapid breathing. (A paper describing the invention was published today in the journal Science Advances.)
Dubbed “inflight fiber printing,” the technique enables the researchers to print the fibers and hook them into a monitoring circuit, all in one step.
“Previously you could have very small conducting fiber production but it could not be incorporated directly into a circuit,” says Shery Huang, a lecturer in bioengineering at the University of Cambridge who led the research. “The main innovation here is we can directly incorporate these small conducting fibers onto the circuit with designable fiber pattern structures,” she says.
When the Spanish flu pandemic swept across the globe in 1918, it ravaged a population with essentially no technological countermeasures. There were no diagnostic tests, no mechanical ventilators, and no antiviral or widely available anti-inflammatory medications other than aspirin. The first inactivated-virus vaccines would not become available until 1936. An estimated 50 million people died.
Today, a best-case scenario predicts 1.3 million fatalities from COVID-19 in 2020, according to projections by Imperial College London, and rapidly declining numbers after that. That in a world with 7.8 billion people—more than four times as many as in 1918. Many factors have lessened mortality this time, including better implementation of social-distancing measures. But technology is also a primary bulwark.
Since January of this year, roughly US $50 billion has been spent in the United States alone to ramp up testing, diagnosis, modeling, treatment, vaccine creation, and other tech-based responses, according to the Committee for a Responsible Federal Budget. The massive efforts have energized medical, technical, and scientific establishments in a way that hardly anything else has in the past half century. And they will leave a legacy of protection that will far outlast COVID-19.
In the current crisis, though, it hasn’t been technology that separated the winners and losers. Taking stock of the world’s responses so far, two elements set apart the nations that have successfully battled the coronavirus: foresight and a painstakingly systematic approach. Countries in East Asia that grappled with a dangerous outbreak of the SARS virus in the early 2000s knew the ravages of an unchecked virulent pathogen, and acted quickly to mobilize teams and launch containment plans. Then, having contained the first wave, some governments minimized further outbreaks by carefully tracing every subsequent cluster of infections and working hard to isolate them. Tens of thousands of people, maybe hundreds of thousands, are alive in Asia now because of those measures.
In other countries, most notably the United States, officials initially downplayed the impending disaster, losing precious time. The U.S. government did not act quickly to muster supplies, nor did it promulgate a coherent plan of action. Instead states, municipalities, and hospitals found themselves skirmishing and scrounging for functional tests, for personal protective equipment, and for guidance on when and how to go into lockdown.
The best that can be said about this dismal episode is that it was a hard lesson about how tragic the consequences of incompetence can be. We can only hope that the lesson was learned well, because there will be another pandemic. There will always be another pandemic. There will always be pathogens that mutate ever so slightly, making them infectious to human hosts or rendering existing drug treatments ineffective. Acknowledging that fact is the first step in getting ready—and saving lives.
The cutting-edge technologies our societies have developed and deployed at lightning speed are not only helping to stem the horrendous waves of death. Some of these technologies will endure and—like a primed immune system—put us on a path toward an even more effective response to the next pandemic.
Consider modeling. In the early months of the crisis, the world became obsessed with the models that forecast the future spread of the disease. Officials relied on such models to make decisions that would have mortal consequences for people and multibillion-dollar ones for economies. Knowing how much was riding on the curves they produced, the modelers who create projections of case numbers and fatalities pulled out all the stops. As Matt Hutson recounts in “The Mess Behind the Models,” they adapted their techniques on the fly, getting better at simulating both a virus that nobody yet understood and the maddening vagaries of human behavior.
In the development of both vaccines and antiviral drugs, researchers have committed to timelines that would have seemed like fantasies a year ago. In “AI Takes Its Best Shot,” Emily Waltz describes how artificial intelligence is reshaping vaccine makers’ efforts to find the viral fragments that trigger a protective immune response. The speed record for vaccine development and approval is four years, she writes, and that honor is held by the mumps vaccine; if a coronavirus vaccine is approved for the general public before the end of this year, it will blow that record away.
Antiviral researchers have it even tougher in some ways. As Megan Scudellari writes, hepatitis C was discovered in 1989—and yet the first antiviral effective against it didn’t become available until 26 years later, in 2015. “Automating Antivirals” describes the high-tech methods researchers are creating that could cut the current drug-development timeline from five or more years to six months. That, too, will mean countless lives saved: Even with a good vaccine, some people inevitably become sick. For some of them, effective antivirals will be the difference between life and death.
Beyond Big Pharma, engineers are throwing their energies into a host of new technologies that could make a difference in the war we’re waging now and in those to come. For example, this pandemic is the first to be fought with robots alongside humans on the front lines. In hospitals, robots are checking on patients and delivering medical supplies; elsewhere, they’re carting groceries and other goods to people in places where a trip to the store can be fraught with risk. They’re even swabbing patients for COVID-19 tests, as Erico Guizzo and Randi Klett reveal in a photo essay of robots that became essential workers.
Among the most successful of the COVID-fighting robots are those buzzing around hospital rooms and blasting floors, walls, and even the air with ultraviolet-C radiation. Transportation officials are also starting to deploy UV-C systems to sanitize the interiors of passenger aircraft and subway cars, and medical facilities are using them to sterilize personal protective equipment. The favored wavelength is around 254 nanometers, which destroys the virus by shredding its RNA. The problem is, such UV-C light can also damage human tissues and DNA. So, as Mark Anderson reports in “The Ultraviolet Offense,” researchers are readying a new generation of so-called far-UV sterilizers that use light at 222 nm, which is supposedly less harmful to human beings.
When compared with successful responses in Korea, Singapore, and other Asian countries, two notable failures in the United States become clear: testing and contact tracing. For too long, testing was too scarce and too inaccurate in the United States. That was especially true early on, when it was most needed. And getting results sometimes took two weeks—a devastating delay, as the SARS-CoV-2 virus is notorious for being spread by people who don’t even know they’re sick and infectious. Researchers quickly realized that what was really needed was something “like a pregnancy test,” as one told Wudan Yan: “Spit on a stick or into a collection tube and have a clear result 5 minutes later.” Soon, we’ll have such a test.
Digital contact tracing, too, could be an enormously powerful weapon, as Jeremy Hsu reports in “The Dilemma of Contact-Tracing Apps.” But it’s a tricky one to deploy. During the pandemic, many municipalities have used some form of tracing. But much of it was low-key and low-tech—sometimes little more than a harried worker contacting people on a list. Automated contact tracing, using cloud-based smartphone apps that track people’s movements, proved capable of rapidly suppressing the contagion in places like China and South Korea. But most Western countries balked at that level of intrusiveness. Technical solutions that trade off some surveillance stringency for privacy have been developed and tested. But they couldn’t solve the most fundamental problem: a pervasive lack of trust in government among Americans and Europeans.
It has been 102 years since the Spanish flu taught us just how bad a global pandemic can be. But almost nobody expects that long of an interval until the next big one. Nearly all major infectious outbreaks today are caused by “zoonotic transfer,” when a pathogen jumps from an animal to human beings. And a variety of unrelated factors, including the loss of natural habitats due to deforestation and the rapid growth of livestock farming to feed industrializing economies, is stressing animal populations and putting them into more frequent contact with people.
We’re unlikely to halt or even measurably slow such global trends. What we can do is make sure we have suitable technology, good governance, and informed communities. That’s how we’ll mount a tougher response to the next pandemic.
This article appears in the October 2020 print issue as “Prepping for the Next Big One.”
Walk into the Cambridge, Ont., office of health-care equipment company PrescientX and you probably wouldn’t suspect you’re entering one of the most sanitary places in North America.
In this otherwise-ordinary Toronto-area office suite, you can disinfect your keys, phone, and other portables at the reception area’s ultraviolet-sterilization stand. In cooler months, the air you breathe is cleansed of mold and bacteria in UV-sterilized heating units as well as blasted by UV fixtures in the office air ducts to eliminate viruses. In-room UV fixtures pointing at the ceiling disinfect the air, while other UV lights that turn on only when no one’s in the room zap pathogens on desks, keyboards, and high-touch surfaces in bathrooms and work spaces.
The office, says PrescientX founder and CEO Barry Hunt, represents a possible future in which pandemics like COVID-19 are more commonplace—but in which germicidal ultraviolet light is one of the most potent weapons we have to face them down.
Fornearly a century and a half, scientists have been investigating ultraviolet light’s deadly effect on germs. In recent times, UV was deployed as a disinfectant against deadly coronavirus particles during the SARS outbreak in 2003. And as soon as the new coronavirus began spreading in earnest in China late last year, UV returned as a potentially powerful weapon to fight this new scourge. While antiviral drugs and vaccines concentrate on minimizing and repelling infections in the body, the ultraviolet systems being deployed focus on killing the virus in the environment, before it has a chance to infect anyone.
Germicidal UV technology is now being used to sterilize air, surfaces, and personal protective equipment like N95 masks. Meanwhile, experts in the field are devoting much of their time to educating the public about the technology’s effectiveness against the coronavirus—and outbreaks and pandemics yet to come. The main hurdle for germicidal UV, says Dean Saputa, vice president and cofounder of UV Resources, a Santa Clarita, Calif.–based UV technology company, “is overcoming the lack of…understanding about this technology.”
For starters, experts point out, not all ultraviolet rays are created equal. Ultraviolet light lies in a region of the electromagnetic spectrum beyond indigo and violet. Anyone who’s read the label on a bottle of sunscreen knows the UV wavelengths that give you a suntan or a sunburn are called UV-A (with wavelengths between 400 and 315 nanometers) and UV-B (315 to 280 nm). Germicidal UV tech focuses on shorter, more energetic UV wavelengths, known as UV-C, which lie between 280 and 100 nm. The Earth’s ozone layer prevents virtually all UV-C light from reaching us. So microbes and viruses (and everything else, really) evolved for millions and billions of years without ever being exposed to these wavelengths.
That changed in 1901, with the invention of the mercury-vapor lamp. It produces a potent wavelength of UV-C light—254 nm—that has proved devastating for nearly any genetic material in its path, including that of a coronavirus or a human.
Much of the trick to wielding germicidal UV light against the spread of disease lies in finding a way to keep people safe from that light. Those involved have already built up a lot of expertise in that area, but new technology could make the job of using UV-C in occupied spaces easier.
While UV-C light has been used successfully against germs for more than a century, it’s only recently that researchers have understood why it’s so successful. In DNA’s four-letter alphabet of nucleotides, thymine (T) and cytosine (C) are particularly susceptible to UV. The UV knocks an electron loose and causes two T molecules or two C molecules to bond together, introducing an error into a string of DNA. Humans have genetic self-repair mechanisms, including a molecule called p53. This protein (sometimes referred to as the “guardian of the genome”) patrols DNA strands and looks for just this kind of nucleotide damage. But p53 can do only so much. Too much damage overwhelms it and can lead to cancer.
SARS-CoV-2, the virus that causes COVID-19, lacks such sophisticated self-repair mechanisms, and its genetic material is made up of RNA rather than DNA. RNA contains uracil instead of thymine, but the effect of UV-C is essentially the same: Genetic damage accumulates and the virus is destroyed.
The main hitch with UV-C light in the 254-nm range is that it penetrates human skin and eyes, leading to skin cancer andcataracts. So UV-C’s DNA-smashing effect means that any disinfecting device that uses it has to be designed to operate either when no one is in the room or in a self-contained space where humans can’t go.
Germicidal UV in most commercial and industrial settings today still comes from mercury-vapor lamps, says PrescientX’s Hunt. These devices have a spectral peak at 254 nm. That emission is the result of an arc of electricity that ionizes (typically) argon gas and vaporizes liquid mercury. Glass would block the radiation, so these lamps are made of quartz instead.
UV-C–emitting LEDs, made from alloys of aluminum nitride, are much newer and have a number of potential advantages over mercury lamps—no toxic mercury, greater durability, faster startup, and emission at a diversity of wavelengths, which may aid in their germicidal role. Most important, though, is UV-C LEDs’ theoretical potential for higher efficiency. That potential is as yet unrealized, however. Jae-hak Jeong, technical research fellow and vice president at Seoul Semiconductor, told IEEE Spectrum that today’s mercury lamps have a higher wall-plug efficiency—electrical power in versus optical power out—than the UV-C LEDs on the market now. But mercury lamps’ advantage is not expected to last, because researchers predict UV-C LEDs to improve in much the same way that blue LEDs did to reach their dominant position in lighting. For now though, UV-C LEDs aren’t powerful enough to sterilize more than small volumes of air or nearby surfaces.
Recent experience with UV-C light confirms what Wells found in the 1930s: Air disinfection with 254-nm UV light is “very effective,” Hunt says. Direct illumination of the air in the upper part of a room produces better throughput than irradiating the air inside HVAC units, he adds. According to the Illuminating Engineering Society, 17 milliwatts of 254-nm-lamp radiation per cubic meter of upper-air space is the evidence-based dose developed to control tuberculosis. However, some bacteria, viruses, and other microorganisms are more resistant to UV-C light than others.
At that dose, upper-air fixtures can destroy germs in the lamps’ direct line of sight “in a matter of seconds,” says Saputa of UV Resources. To keep humans safe, the fixtures, which typically cost a few thousand dollars each, are placed at heights above 2 meters, and nonreflective baffles direct the ultraviolet energy upward and outward. (UV-C reflects poorly off of most surfaces, so there’s little danger of exposure from rays bouncing off ceilings and other fixtures; nonetheless, installers must make sure by using UV-C meters.) Such installations can be used in a variety of settings, including patient rooms, waiting rooms, lobbies, stairwells, and emergency-room entrances and corridors.
Air isn’t the only thingthat needs disinfecting.During the pandemic, UV-wielding robots in hospitals and UV germ zappers in airplanes andsubway cars have joined a host of technologies being rolled out to disinfect surfaces.
The main difference between these systems and UV air sterilizers is that the former can’t operate when people are present, so they’re not continuously keeping areas virus-free. “Design engineers must keep in mind disinfection only lasts until people are placed into that hospital bed or sit in that airplane seat,” says Saputa.
But sporadic disinfection is preferable to none at all. Before this year, Carlsbad, Calif.–based Cleanbox Technology had been developing a UV-C LED box to sterilize virtual-reality and augmented-reality headsets. The company’s system was readily adaptable to sterilizing N95 masks, says Cleanbox’s chief technology officer and cofounder David Georgeson.
The result, the CleanDefense N95 sanitizing light box, can hold four masks at a time. The box is portable and powered from the wall or a battery bank, enabling use in mobile environments like ambulances and airplanes as well as in health care settings, restaurants, and shopping centers.
The challenge with this technology and any other type of UV disinfection is that “the radiation has to actually strike the virus to break the [RNA] and inactivate it,” says Robert Karlicek, director of Rensselaer Polytechnic Institute’s Center for Lighting Enabled Systems & Applications, in Troy, N.Y. “If those virus particles are sitting behind dirt or covered by another fiber, you’d have to scatter a lot of light before you got a good kill rate.”
The problem is illustrated by what’s called the “canyon wall” effect. To bacteria and viruses, textural features on common surfaces can be like 100-meter-deep canyons would be to us. In experiments with surfaces having submillimeter texture, UV-C’s kill rate against the bacteria Staphylococcus aureus varied as much as 500-fold depending on the angle at which the mercury lamp’s light fell.
That dependence on angle is why it typically takes three UV systems to disinfect a hospital room, according to Marc Verhougstraete, assistant professor of public health at the University of Arizona. Even then, there are still unexposed areas. So for that application, UV-C surface sanitizers should be part of a system that includes routine surface disinfection, hand hygiene, and air treatment, he says.
Getting a thorough dosage from more than one angle is key to sanitizing N95 masks for reuse. Karlicek and his team developed a mercury-lamp N95-mask sterilizer that was tested at Mount Sinai Hospital in New York City. It uses two sets of UV lamps to irradiate the front and back of the masks at the same time. PrescientX is also getting into the N95-mask-sterilization business with a UV-C light box called Terminator CoV. And there are other systems in various states of development and commercialization as well.
Those studies all found that irradiating masks with 1 to 2 joules of UV-C energy per square centimeter was sufficient to inactivate between 99.9 and 99.99 percent of the virus particles on the mask. That said, eliminating coronavirus particles is not just a numbers game. If the sterilization unit casts any shadows on the mask, that mask will not be fully disinfected. That’s why these systems are designed with fasteners and hooks that stretch the mask and minimize shadows.
“You need intensity and geometry to get rid of the virus,” Hunt says.
Given the harmful effects of 254-nm UV-C, scientists are exploring the higher-energy wavelength of 222 nm, in the far-UV region. This wavelength has been found to kill viruses and bacteria, and initial studies show that it’s substantially safer than photons in the 254-nm range. In fact, far-UV may be able to safely bathe an entire room in sterilizing light, even with people present.
Far-UV light at 222 nm “hardly penetrates the outer layer of skin,” says David Sliney, retired manager of the U.S. Army’s Laser and Optical Radiation Program at the Army Public Health Center, near Baltimore. “It’s heavily absorbed by protein. But there is some evidence that it may even be more effective against airborne viruses” than other UV light. The wavelength appears to be safe for the eyes as well because it penetrates no deeper than the layer of tears that coat the eye. A 2019 study of albino rats in Japan found prolonged far-UV exposure induced no skin or eye damage.
At present, far-UV is generated by krypton-chlorine excimer lamps. (“Excimer” is a portmanteau of “excited” and “dimer,” meaning an excited state of a two-part molecule.) Inside the sealed quartz-glass chamber of such a lamp, krypton and chlorine are heated by electric discharge whose energy is sufficient to momentarily create a KrCl excimer, which spits out a 222-nm spectral line before dissociating again.
However, these light sources don’t just give off far-UV light. “Excimer lamps produce a peak at 222 nm, but they also produce [longer]-wavelength light,” explains David Brenner, director of Columbia University’s Center for Radiological Research, in New York City. “And that is damaging, because it doesn’t have the protective properties of 222 nm. It can penetrate [skin] and damage DNA.”
Filters can eliminate the extraneous wavelengths, but Brenner says a better solution would be a far-UV LED lamp with a narrow spectral profile right at 222 nm. Such an LED does not yet exist. “LEDs have been coming down in wavelength for a long time,” he says. “Once you go down below 250, 240, 230 [nm], the efficiency falls off dramatically. It’s like a cliff.”
So in the near term, excimer lamps are the best hope. Brenner expects such lamps to be on the market by the end of this year or early 2021.
Despite thisarsenal of ultraviolet technologies—UV-C LEDs, mercury vapor lamps, and KrCl excimer lamps—the current pandemic may yet come and go before the world has rolled out germicidal UV broadly enough to make a big impact. And so experts are already planning for the next dangerous pathogen, and when it comes, they hope to greet it with a phalanx of UV air purifiers and surface sterilizers in hospitals, airports, public transit, offices, schools, nursing homes, stores, restaurants, elevators, and elsewhere. The ubiquity of UV technology should make it much harder for an outbreak to spread, perhaps preventing a lethal contagion from ever becoming a pandemic.
This article appears in the October 2020 print issue as “The Ultra-Violet Offense.”
In June, as the coronavirus swept across the United States, Paloma Beamer spent hours each day helping her university plan for a September reopening. Beamer, an associate professor of public health at the University of Arizona, was helping to test a mobile app that would notify users if they crossed paths with confirmed COVID-19 patients.
A number of such “contact tracing” apps have recently had their trials by fire, and many of the developers readily admit that the technology has not yet proven that it can slow the spread of the virus. But that caveat has not stopped national governments and local communities from using the apps.
“Right now, in Arizona, we’re in the full-blown pandemic phase,” Beamer said, speaking in June, well before the new-case count had peaked. “And even manual contact tracing is very limited here—we need whatever tool we can get right now to curb our epidemic.”
Traditionally, tracers would ask newly diagnosed patients to list the people they’d spent time with recently, then ask those people to provide contacts of their own. Such legwork has helped to control other infectiousdisease outbreaks, such as syphilis in the United States and Ebola in West Africa. However, while these methods can extinguish the first spark or the last embers of an epidemic, they’re no good in the wildfire stage, when the caseload expands exponentially.
That’s the reason to automate the job. Digital contact tracing may also jog fuzzy memories by dredging up relevant information on where a patient has been, and with whom. Some technologies can go further by automatically alerting people who have been in close proximity to a patient and thus may need to get tested or go into isolation. Speedy notification is particularly important during the COVID-19 pandemic, given that asymptomatic people seem capable of transmitting the virus.
Automatic alerts may sound great, but there are “limited real-world use cases” and “limited evidence for their effectiveness,” says Joseph Ali, associate director for global programs at the Johns Hopkins Berman Institute of Bioethics and coauthor of the book Digital Contact Tracing for Pandemic Response, published in May. Rushed deployment of unproven technologies runs the risk of misidentifying moments of exposure that in fact never happened—false positives—and missing moments that did happen, or false negatives.
Some governments have embraced these apps; others have struggled with the decision. The United Kingdom, for example, initially spent millions developing an app that would collect data and send it to a centralized data storage system run by the National Health Service. But privacy advocates raised concern about the system, and in June the government announced that it would abandon that effort and switch to a less-centralized alternative built on technology from the tech giants Apple and Google.
The U.K.’s indecision shows how the choice of strategy revolves around privacy trade-offs. Some countries have staked everything on effectiveness and nothing on privacy.
Wuhan, the Chinese city at the heart of the pandemic, squashed the virus, eased the lockdown, then saw a small resurgence of the contagion in May. Public-health authorities went all out: They tested the entire population of 11 million and instituted the tracking of each person’s movements. Would-be customers could enter a shop only by having their temperature taken and exchanging personal bar codes, displayed on their phones, with the shop’s own identifying barcode. They then had to repeat the exchange upon leaving. That way, if anyone in the shop ended up testing positive, the authorities would be able to find whoever was in the same place at the same time, test those people, and, if necessary, quarantine them.
It worked. As of mid-July, Wuhan was reporting that no new cases of the virus had been recorded for 50 consecutive days. But such a gargantuan effort is not always an option. In many parts of the world, most people will willingly participate only if they trust in the system.
In an online survey of Americans conducted by Avira, a security software company, 71 percent of respondents said they don’t plan to use a COVID contact-tracing app. Respondents cited privacy as their main concern. In a telling contrast, 32 percent said they would trust apps from Google and Apple to keep their data secure and private—but just 14 percent said they would trust apps from the government.
One shining example of effective digital contact tracing is South Korea, which built a centralized system that scrutinized patients’ movements, identified people who had been in contact with patients, and used apps to monitor people under quarantine. To date, South Korea has successfully contained its COVID-19 outbreaks without closing national borders or imposing local lockdowns.
The South Korean government’s system gave contact tracers access to multiple information sources, including footage from security cameras, GPS data from mobile phones, and credit card transaction data, says Uichin Lee, an associate professor of industrial and systems engineering at the Korea Advanced Institute of Science and Technology (KAIST), in Daejeon. “This system helps them to quickly identify hot spots and close contacts,” Lee says.
But South Korea’s system also publicly shares patients’ contact-trace data—including pseudonymized information on demographics, infection information, and travel logs. This approach raises serious privacy concerns, as Lee and his colleagues outlined in the journal Frontiers in Public Health. The travel logs alone could enable observers to infer where a patient lives and works.
By comparison, public-health authorities in Europe and the United States have shied away from publicly sharing such patient data. There’s also a middle way: A person’s phone may store data identifying people or location, and it may be left to the owner of the phone whether to share that information with public-health officials.
And then there’s the radical idea of not storing such data at all. That’s the approach taken by the Google/Apple Exposure Notification (GAEN) system. As these tech giants own, respectively, the Android and iOS smartphone standards, the GAEN system enables independent developers to build apps that can run on either standard. The system records Bluetooth transmissions between phones in close proximity to one another, and stores that data as anonymized beacons on each phone for a limited time. If one phone user tests positive for COVID-19 and enters that positive status in a mobile app built upon GAEN, the system will alert other phone users who have been in close proximity within the potentially infectious time period.
To protect user privacy, the system does all these things without ever recording the exact location of such encounters. It also limits the reported exposure time for each encounter to 5-minute increments, with a maximum possible total of 30 minutes. That constraint makes it more difficult for users to guess the source of their exposure.
The GAEN system also appeals to those wary of increased surveillance in the name of public health. Germany, Italy, and Switzerland have already deployed exposure-notification apps based on GAEN, and other countries will likely follow. In the United States, Virginia was the first to introduce one.
“If you collect identifying information along with Bluetooth data, it could potentially lead to new forms of surveillance,” says Tina White, founder and executive director of the nonprofit COVID Watch and a Ph.D. candidate at the Stanford Institute for Human-Centered Artificial Intelligence. “And that’s exactly what we don’t want to see.” COVID Watch is working with the University of Arizona on a privacy-centric app based on the GAEN system. Preliminary testing involving two phones placed at different indoor locations has ramped up to more real-life campus scenarios inside classrooms, dining halls, and the Cat Tran student shuttle, followed by a campuswide rollout in mid-August.
There’s one big hitch: Repurposing Bluetooth from its original communication function poses serious technical difficulties. At Trinity College Dublin, researchers found that Bluetooth can perform poorly on the crucial task of proximity detection when a phone is in the presence of reflective metal surfaces. In one experiment on a commuter bus, a Swiss COVID-19 app built on the GAEN system failed to trigger exposure notifications even though the phones were within 2 meters (a little over 6 feet) of each other for 15 minutes.
“Public transport, which seems kind of mundane, is actually one of the core use cases for contact-tracing apps, but it’s also a terrible radio environment,” says Douglas Leith, a professor of computer science and statistics at Trinity College. “All our measurements suggest that it probably won’t work on buses and trains.”
Another problem is the variation in antenna configuration over the thousands of Android phone models. Engineers must calibrate the software to make up for any loss in signal strength, Leith explains. And although Bluetooth-signal “chirps” require minimal power, simply listening for such chirps requires that the main phone processors be turned on, which can quickly drain battery power unless the apps are restricted to short listening periods.
Beyond the technical challenges faced by Bluetooth-based apps, all contact-tracing apps suffer from the same general problem: Unless a certain percentage of the population installs an app, it can’t do its work. People won’t opt in unless they believe in the public-health strategy behind an app and in the personal advantages they can hope to gain from it. Making that sale has been tough. In Germany, which has had some of the best results of any country in containing the virus, only 41 percent of the population has said it was willing to download what is known as the Corona-Warn-App.
Some researchers point to a University of Oxford study that modeled the coronavirus’s spread through a simulated city of 1 million people; it found that 60 percent adoption is needed to stop the pandemic and keep countries out of lockdown (although the study suggested that lower rates of adoption could still prove helpful).
The tech giants are making widespread adoption easier by deploying an app-less Exposure Notifications Express function for iOS and Android devices. If a phone user opts in, the phone begins listening for nearby Bluetooth beacons from other phones. And later, if a stored Bluetooth beacon proves to be a match for someone confirmed to be positive for COVID-19, the system will prompt the user to download an exposure-notification app for more information.
Bluetooth is not the only way forward. The COVID Safe Paths project led by the nonprofit PathCheck Foundation, an MIT spin-off, has been developing and fielding a mobile app that uses GPS location data instead. The GPS approach provides more location data than Bluetooth does, in exchange for less user privacy. But Safe Paths also aims to build a Bluetooth-based version with the GAEN system. “We have been mostly agnostic to the technology we want to use,” says Abhishek Singh, a Ph.D. candidate in machine learning at the MIT Media Lab and a member of Safe Paths.
“It matters less what’s actually happening in the back end, and more about communication and perception,” says Kyle Towle, a member of the technology team at Safe Paths and former senior director of cloud technology at PayPal. The crucial component, he says, is the “appeal to our community members to gain that trust in the first place.”
The best path to success may come from ample preparation. South Korea’s experience with an outbreak of Middle East respiratory syndrome (MERS) in 2015 prompted the government to update national laws and lay the bureaucratic and technological foundations for an efficient contact-tracing system. The resulting public-private partnership enables human contact tracers to pull together digital data on a suspected or confirmed case’s travel history within 10 minutes.
“A country like South Korea, maybe because they went through this before with other viruses five years ago, really got a head start, and they didn’t mess around,” says Marc Zissman, associate head of the cybersecurity and information sciences division at MIT Lincoln Laboratory. The lab is among those in the PACT (Private Automated Contact Tracing) project, which is testing GAEN’s Bluetooth-based app performance.
Zissman says that developing digital contact tracing during a pandemic is like building a plane and flying it at the same time while also measuring how well everything works. “In a perfect world, something like this would have taken a couple years to implement,” he says. “There just isn’t the time, so instead what’s happening is people are doing the best they can, and making the best engineering judgments they can, with the data they have and the time that they have.”
This article appears in the October 2020 print issue as “The Dilemma of Contact-Tracing Apps.”
In the early days of the coronavirus pandemic, it wasn’t just face masks and hand sanitizer that flew off drugstore shelves. Pulse oximeters were also in short supply, as news came out that a drop in blood oxygen could be a sign that a case of the coronavirus has taken a bad turn.
These inexpensive and noninvasive electronic devices use LED lights and photodiodes to determine the way red blood cells are absorbing light—oxygenated cells absorb more infrared light than red light, cells that aren’t carrying oxygen the opposite. With that information, algorithms can calculate a level of blood oxygenation; for most healthy people that’s in the high 90 percentile, in cases of Covid, the numbers dropped into the 80s. So it seemed like a good idea to have one on hand, if you could find one.
Now, six-plus months into the pandemic, it’s not surprising that consumer electronics manufacturers are touting the benefits of adding pulse oximeters to wearables. The sensors don’t cost much, they don’t use much battery power, and they could attract at least a few consumers looking to feel a little safer in this uncertain world.
Apple is the latest company to bring pulse oximetry to a wrist wearable (Fitbit and Garmin already had products out pre-pandemic, aimed at identifying sleep apnea). Announced last week, the Apple Watch Series 6 uses four groups of green, red, and infrared LEDs along with four photodiodes and what the company says is an advanced custom algorithm to determine blood oxygenation. (The red and infrared LEDs are involved in the oxygen measurement; the green LED can check pulse rate.) The sensors, mounted on the back of the watch and therefore touching the top of the wrist, can be used to take readings on demand during the day and automatically during sleep.
Apple is touting the gadget for “fitness and wellness.” Loosely translated, that means that this gadget does not have FDA approval to be marketed as a medical device. That comes as little surprise—FDA clearance takes time—but without that approval, it’s hard to know just how accurate it is.
Indeed, accuracy remains a question with many of the pulse oximeters on the consumer market. Says Steve Xu, a physician-engineer who is medical director for the Center for Bio-Integrated Electronics at Northwestern University, “It is relatively straightforward to make a pulse oximeter, even for an undergrad engineering design project, but it is really really hard to make a good one that is clinically dependable.”
Is Apple’s a good one? It’s hard to say just yet. Besides the issues of adjusting to different skin colors, coping with motion, and other design challenges faced by all pulse oximeters, putting the sensors on top of the wrist raises the difficulty level. The devices used in hospitals as well as the standalone gadgets sold in drugstores typically clip onto a fingertip or, sometimes, an earlobe.
“Those locations have an advantage over the back of the wrist,” Xu says, “because they have more capillaries, so provide a better signal to noise ratio.”
Wrist-worn blood oxygen sensors face another disadvantage: while fingertips are thin enough to allow light to shine through them, wrist oximeters must rely on reflected light, an inherently less precise approach.
“It’s not necessarily bad,” Xu says, “but all things being equal, isn’t going to be as accurate” as a pulse oximeter designed for a more favorable location.”
“I would never put a pulse oximeter on the wrist,” says William McMillan, co-founder, president, and chief scientific officer of Profusa, a company developing implantable biosensors. “The wrist is subject to a lot of motion, which is bad news for continuous measurement.” (Apple’s watches do have motion sensors which could help it identify quiet moments.)
Apple can show proof that its watch-based device can provide accurate oxygen saturation reading by taking it through FDA’s approval process, says Xu; the testing procedure for pulse oximeters is well-established.
Even without such vetting, Apple is launching several health studies using the Apple Watch oximeter—one looking at the management of heart failure, one at the management of asthma, and one considering blood oxygen level changes as early warning signs of Covid-19 and influenza. Both Xu and McMillan are cautiously optimistic about such efforts.
“Consumer product companies like Apple and Fitbit have a vastly bigger scale than most medical device companies,” Xu says. “Not many technology companies outside of the Apples and Fitbits and Samsungs can deploy a million devices in the world and manage the data that comes in. So we should do these studies and see how prognosticating they are, but we should realize there will be a lot of false positives. Maybe it will turn out to be a useful screening tool, but the verdict is still out.”
“Because [the device] isn’t likely terribly accurate, and it won’t involve a control group, rather, an uncontrolled situation, they will need a huge sample size to detect any phenomena,” says McMillan. “But they end up having millions of data points in which to look for insights, and that would be OK.”
This all begs the question—does the average smart watch user actually need to wear a pulse oximeter 24/7?
While such a wearable may tell us more about the fluctuations of blood oxygen saturation in the broad population, Xu says, “The vast number of healthy people are at 97 to 99 percent. If we all wear these and freak out whenever it drops to 92, the potential to worry people who are well is much higher than the clinical implications, which at this point are unknown.”+
Researchers are focusing more and more attention on using artificial intelligence to discover and design new medicines, and a new start-up with strong backing announced last week that it is jumping into the field with big ambitions.
Cambridge, Massachusetts–based Generate Biomedicines, which emerged from stealth mode on 10 September, says it is using machine learning algorithms and big data to design biological compounds to combat 50 of the top targets associated with disease. The company is also developing candidates for therapies that would fight SARS-CoV-2, the virus that causes COVID-19.
Generate Biomedicines is backed by Flagship Pioneering, a funder and builder of start-up companies. It’s roster includes Moderna, which is a leader in the race to develop a vaccine against COVID-19.
“We are creating new molecular entities, and generating molecules that you wouldn’t be able to discover through traditional means,” says Molly Gibson, co-founder and chief innovation officer at Generate Biomedicines. “We think this type of technology breaks you away from that discovery paradigm of searching through existing molecules or searching through close relatives of existing molecules.”
Traditional protein drug discovery methods, such as high-throughput screening, involve a lot of trial and error. Algorithms and high powered computing could greatly shrink the amount of time scientists spend searching for new drug candidates.
“If you can compute sequences in silico, you’re speeding up the time it takes to come up with an effective candidate,” says Gini Deshpande, founder and CEO of AI-based drug discovery company NuMedii, who is not involved with Generate Biomedicines. “There are a number of players in this space coming at it from different angles,” Deshpande says, noting that there is a huge unmet need for technologies that can reduce the time and cost of drug development.
Deshpande says that there are at least 17 different companies using machine learning to aid the discovery of biologics, or protein-based drugs—the kind of medicines on which Generate Biomedicines is focused. Deshpande estimates that over 200 more companies are applying AI to small molecules—a category of drugs characterized by their low molecular weight. “So they’re certainly not the only player in the space,” she says.
Avak Kahvejian, founding co-CEO of Generate Biomedicines, says his company stands out in part because its machine learning platform is capable of teasing out “the true, underlying foundational principles by which proteins operate,” he says. Other companies “are using machine learning to find useful relationships in data.”
The company’s computational platform is trained on a vast database of known proteins: 160,000 protein structures and 190 million protein genetic sequences, according the company. The system looks for statistical patterns linking a protein’s genetic sequence, three-dimensional structure, and function, and develops a set of governing rules for those patterns—similar to the way algorithms process natural language and images.
After learning, the system can then be focused on the synthesis of new, custom proteins with therapeutic potential. The platform continually learns from every new protein generation campaign through a generate-build-test cycle.
“With this vast amount of training and learning, we can now run the process forward, and use it to generate a number of beautiful solutions that are unimaginable today—undesignable by the human hand,” says Kahvejian. “These general rules are much more valuable, as it means you don’t have to reinvent the wheel every time you see a new class of proteins. It also means you can immediately sample from all the sets of protein classes that nature never invented.”
Generate Biomedicines’s drug candidates will include proteins of any variety—such as antibodies, peptides, enzymes, and cytokines—that can bind to, disable, or activate biological targets associated with disease. The company aims to take its drugs all the way through human trials and to market, says Kahvejian. “The breadth [of possible therapies] is enormous and daunting, and it’s nothing one company can really commercialize in and of itself,” he says. “So partnering will be part of the strategy.”
In response to the COVID-19 pandemic, Generate Biomedicines has applied its platform to designing antibodies and peptides that can neutralize the SARS-CoV-2 virus. “We immediately jumped on trying to figure out what’s known about the virus and the protein structures involved in its infectivity, and use our platform to generate antibodies to block those structures,” says Kahvejian. Those antibodies are now being tested in the lab in collaboration with the Coronavirus Immunotherapy Consortium, he says.
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