How bacteria-fighting viruses could go mainstream

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Lynn Cole had a blood infection she couldn’t shake. For years, she was in and out of the hospital. Each time antibiotics would force the infection to retreat. Each time it came roaring back.

In the summer of 2020, the bacteria flooding Cole’s bloodstream stopped responding to antibiotics. She was running out of time. Her doctors decided they had to try a different approach, and asked the US Food and Drug Administration  to allow them to administer an experimental therapy, a virus known as a bacteriophage. Bacteriophages — or phages — are tiny viruses that infect and destroy bacteria.

What happened next? The details came out this week in a case study in mBio. The phages worked. Cole recovered with remarkable speed. But then the therapy failed. Cole’s case highlights the enormous promise of phage therapy, but it also shows just how much we have to learn.

Welcome back to the Checkup. Let’s talk phages. (Or rather, let’s talk about phages again.) What will it finally take to bring phage therapy into mainstream medicine?

Phage therapy has been around for more than a century, but it fell out of fashion throughout most of the world with the advent of antibiotics. The deepening antimicrobial crisis, however, has rekindled people’s interest and generated an enormous amount of excitement. Headlines have claimed that phages can “save the world” and that “one day, doctors might prescribe viruses instead of antibiotics.”

The excitement reached a fever pitch in recent years because of one particularly compelling story. In 2016, HIV researcher Tom Patterson picked up a deadly antibiotic-resistant infection in Egypt. His wife, infectious disease epidemiologist Steffanie Strathdee, helped hunt for the phage therapy that ultimately cured him. Strathdee gave a TED talk. She and Patterson wrote a book. She told her story in People magazine.

Stories like this have cast phages as a miracle cure. And these tiny viruses do have a lot of things going for them. They target bacteria with stunning specificity. “We think of phage as a targeted missile,” says Daria Van Tyne, an infectious disease researcher at the University of Pittsburgh and co-author of  the new case study. This missile can “take out a specific species or strain that is causing the infection, but to leave other commensal bacteria unharmed.” What’s more, phages aren’t as likely to drive bacterial resistance as antibiotics. And they’re wildly abundant. “You can go to a drop of seawater and find trillions of phages,” Van Tyne adds.  

But for many people, phages aren’t some miraculous elixir.  In 2022, researchers published the largest series of case studies of phage therapy for antibiotic-resistant bacterial infections yet. Of the 20 people treated with phages, most with infections related to cystic fibrosis, 11 had a positive response to the therapy. However, only five managed to totally clear their infections. Another six had some partial response. The rest failed to respond or their results were inconclusive. 

Let’s go back to Lynn Cole.

When Cole first received phage therapy, she had been dealing with a blood infection for nearly a month. Her doctors tried a variety of antibiotics with no effect. But 24 hours after they administered phage therapy, Cole’s infection was gone. She seemed cured.

About a month later, however, the infection returned. So the researchers found another phage that would work against the Enterococcus bacteria causing Cole’s infection, and began administering both phages. That seemed to do the trick.

For four months, Cole was infection-free. She left the hospital and went on vacation with her family. But then the infection returned. Cole was out of options. She entered hospice, and seven months later she died of pneumonia.

Van Tyne and her colleagues have spent the past couple of years trying to explain why their phages failed. They don’t yet have an answer, but they do have a hypothesis. A couple of weeks after Cole began receiving the second phage, she developed antibodies against both phages. “Possibly that played a role in limiting how well they were able to find their bacterial targets and kill them,” says Madison Stellfox, a physician and postdoc in Van Tyne’s lab. She posits that perhaps the antibodies coated the phages so they couldn’t enter the bacteria. Or maybe they helped the body clear the phages faster, so they didn’t have time to work.

Cole isn’t the only patient Van Tyne and her colleagues at the University of Pittsburgh have treated. Since Van Tyne started her own lab in 2018, she has developed a library that contains about 200 phages, most isolated from Pittsburgh’s wastewater. Those phages target six or seven species of bacteria. They use that library to develop personalized therapies for patients with life-threatening infections. “We’re trying to match clinical isolates from infected patients with phages that are active on them,” Van Tyne says. 

The team has treated nearly 20 patients. Some have cleared their infections. Some, like Cole, have experienced temporary improvements. Some have had no response at all. But reassuringly, no one has been harmed by the therapy itself.  

All these patients were treated under the FDA’s “compassionate use” program, which provides access to investigational therapies for people with life-threatening illnesses. Case studies can provide valuable insights, but they’re not a pathway to regulatory approval. To move phages into mainstream medicine, we need clinical trials.

Alexander Sulakvelidze, president and chief executive officer at the phage company Intralytix, has been working to develop phage products since the 1990s. In the Republic of Georgia, where he was born, phage therapy is routinely used to treat infections.  

But in the US phage therapy was a hard sell. Intralytix, which launched in 1998, started with baby steps, first seeking approval for phage products to fight bacterial contamination in food products. Now, however, the company is generating revenues, and it has three clinical trials underway to test phage cocktails against three antibiotic-resistant bacteria. But these are trials to assess safety, not the large pivotal trials needed for FDA approval. “That’s why I’m saying it will be several years until [these therapies] see the light of  day,” Sulakvelidze says.

The Los Angeles-based company Armata Pharmaceuticals, led by Deborah Birx (yes, that Deborah Birx), is also testing its phage therapies in trials. The company plans to launch an efficacy study, which could be used to seek regulatory approval, in the coming year, although it has yet to find a partner to help fund that endeavor. This kind of pivotal trial will help get pharma interested in phage therapy, and “that’s the only way it’s going to get completely commercialized,” Birx says. A pivotal trial will also provide some solid data on whether phages are effective. “It is worth moving forward to get a definitive answer,” she adds. “Because otherwise we’re just going to wait, and we’ll be sitting here 20 years from now saying ‘are phages important or not?’”

Read more from MIT Technology Review’s archive

Dig way back in our archives, and you’ll find a piece from 2001 about how phages could be turned into a new class of antibiotics. Paroma Basu has the story. 

Last year, in a previous issue of the Checkup, Jessica Hamzelou  wrote about the comeback of phage therapy. 

A phage cocktail saved a teen with cystic fibrosis from an antibiotic-resistant infection. Charlotte Jee gave us the details in 2019.

DNA sequencing and AI could make it easier for doctors to match infections with the right phage cocktail, Emily Mullin wrote in 2018. 

From around the web

The CDC plans to ditch its Covid five-day isolation policy in favor of a policy that is based on symptoms. The new policy would allow people to stop isolating once their symptoms are mild and they’ve been fever-free for at least 24 hours without medication. (Washington Post)

Dengue is surging in Brazil, prompting Rio de Janeiro to declare a public health emergency. (NYT)

Deep dive: Environmental DNA could help provide an early warning of the next pandemic. (Undark)

A journal retracted three abortion studies that suggested that medication abortion is dangerous after it found that the conclusions were based on faulty assumptions and a misleading presentation of the data. (NYT)

Why engineers are working to build better pulse oximeters

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Visit any health-care facility, and one of the first things they’ll do is clip a pulse oximeter to your finger. These devices, which track heart rate and blood oxygen, offer vital information about a person’s health. But they’re also flawed. For people with dark skin, pulse oximeters can overestimate just how much oxygen their blood is carrying. That means that a person with dangerously low oxygen levels might seem, according to the pulse oximeter, fine.

The US Food and Drug Administration is still trying to figure out what to do about this problem. Last week, an FDA advisory committee met to mull over better ways to evaluate the performance of these devices in people with a variety of skin tones. But engineers have been thinking about this problem too. In today’s Checkup, let’s look at the problem with pulse oximeters—why they are biased and what technological fixes might be possible.

To understand the problem, you first have to understand how pulse oximeters work. Most of these devices clamp onto some part of the body—usually a fingertip, but sometimes they need to be placed on earlobes or toes. One side of the clamp contains LEDs that emit light in two different wavelengths—red and infrared. A sensor on the other side of the clamp measures how much of that light passes through the tissue. The hemoglobin in oxygenated blood and deoxygenated blood absorbs these wavelengths differently, and by calculating the ratio of the red-light measurements to the infrared-light measurements—the R value—the device can tabulate blood oxygen saturation.

Here’s the problem: other factors can affect how much light is absorbed. Dark nail polish, for example, can throw off the reading. Or tattoos. Or melanin. “If a person has a darker skin tone, they’re going to be absorbing more light,” says Maggie Delano, an engineer at Swarthmore College who is interested in inclusive engineering design. Imagine there are 100 photons of light going through a finger. Some get absorbed by blood, some by bone, and some by melanin in the skin. “So if someone has a darker skin tone, maybe five photons get through instead of 20,” Delano says. “If your electronics don’t compensate for that in some way, there can be errors in that result.”

Those errors can have real clinical consequences. Blood oxygen is one of the key vital signs doctors use to determine whether someone needs to receive oxygen or be admitted to the hospital.   

Engineers are working to fix this problem in a variety of ways. At Tufts, Valencia Koomson and her colleagues have developed a device that can detect when the signal quality is poor or when the user has a darker skin tone and compensate by sending more light through. “We’re dealing with very weak optical signals that have to transverse through tissues with lots of [other] elements that absorb and scatter light,” she told Inverse. “It’s very similar to when you’re riding a car and you go through a tunnel. You lose signal because of the absorption of the materials in the tunnel, such that the signal being transmitted from the cell-phone tower is too weak to be processed by your phone.”

Koomson and her colleagues are collaborating with a medical-device manufacturing company to develop a prototype for clinical trials. Because their team was named a finalist in a recent challenge by Open Oximetry, they’ll be able to validate the device for free in the Hypoxia Lab at the University of California, San Francisco.

Meanwhile, engineers at Brown University are trying to find a workaround using special LEDs that can emit polarized light beams. Jesse Jokerst, an engineer at the University of California, San Diego, is working on an oximeter that uses light and sound, and also corrects for skin tone. Another team at the University of Texas at Arlington is hoping to swap the standard red light in pulse oximeters for green light, which bounces back instead of being absorbed. At Johns Hopkins, engineers have developed a prototype pulse oximeter that factors in skin tone when calculating blood oxygen saturation.

Neal Patwari, a mechanical engineer at Washington University in St. Louis, wants to keep the pulse oximeter’s hardware the same, but swap out the algorithm. A pulse oximeter takes four different measurements, two in each wavelength. One measurement takes place as the heart pushes blood through the arteries, when blood flow is at a maximum, and the other happens between pulses, when blood flow is at a minimum. Those four numbers get fed into an algorithm that calculates ratios—actually, one ratio divided by another. That gives you the R value. But, “when you take two numbers and divide them, you can get some strange effects when the denominator is noisy,” Patwari says. And one of the factors that can increase noisiness is darkly pigmented skin. He hopes to find an algorithm that doesn’t rely on ratios, which could offer up a less biased R value. 

Whether any of these strategies will fix the bias in pulse oximeters remains to be seen. But it’s likely that by the time improved devices are up for regulatory approval, the bar for performance will be higher. At the meeting last week, committee members reviewed a proposal that would require companies to test the device in at least 24 people whose skin tones span the entirety of a 10-shade scale. The current requirement is that the trial must include 10 people, two of whom have “darkly pigmented” skin.

In the meantime, health-care workers are grappling with how to use the existing tools and whether to trust them. In the advisory committee meeting on Friday, one committee member asked a representative from Medtronic, one of the largest providers of pulse oximeters, if the company had considered a voluntary recall of its devices. “We believe with 100% certainty that our devices conform to current FDA standards,” said Sam Ajizian, Medtronic’s chief medical officer of patient monitoring. A recall “would undermine public safety because this is a foundational device in operating rooms and ICUs, ERs, and ambulances and everywhere.”

But not everyone agrees that the benefits outweigh the harms. Last fall, a community health center in Oakland California, filed a lawsuit against some of the largest manufacturers and sellers of pulse oximeters, asking the court to prohibit sale of the devices in California until the readings are proved accurate for people with dark skin, or until the devices carry a warning label.

“The pulse oximeter is an example of the tragic harm that occurs when the nation’s health-care industry and the regulatory agencies that oversee it prioritize white health over the realities of non-white patients,” said Noha Aboelata, CEO of Roots Community Health Center, in a statement. “The story of the making, marketing and use of racially biased pulse oximeters is an indictment of our health-care system.”

Read more from MIT Technology Review’s archive

Melissa Heikkilä’s reporting showed her just how “pale, male, and stale” the humans of AI are. Could we just ask it to do better? 

No surprise that technology perpetuates racism, wrote Charlton McIlwain in 2020. That’s the way it was designed. “The question we have to confront is whether we will continue to design and deploy tools that serve the interests of racism and white supremacy.”

We’ve seen that deep-learning models can perform as well as medical professionals when it comes to imaging tasks, but they can also perpetuate biases. Some researchers say the way to fix the problem is to stop training algorithms to match the experts, reported Karen Hao in 2021. 

From around the web

The high lead levels found in applesauce pouches came from a single cinnamon processing plant in Ecuador. (NBC)

Alternating arms for your covid vaccines might offer an immunity boost over sticking to the same arm, according to a new study. (NYT)

Weight loss through either surgery or medication lowers blood pressure, according to new research. (CNN)

Pharma is increasingly building AI into its businesses, but don’t expect that to lead to instantaneous breakthroughs. (STAT)

Why engineers are working to build better pulse oximeters

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Visit any health-care facility, and one of the first things they’ll do is clip a pulse oximeter to your finger. These devices, which track heart rate and blood oxygen, offer vital information about a person’s health. But they’re also flawed. For people with dark skin, pulse oximeters can overestimate just how much oxygen their blood is carrying. That means that a person with dangerously low oxygen levels might seem, according to the pulse oximeter, fine.

The US Food and Drug Administration is still trying to figure out what to do about this problem. Last week, an FDA advisory committee met to mull over better ways to evaluate the performance of these devices in people with a variety of skin tones. But engineers have been thinking about this problem too. In today’s Checkup, let’s look at the problem with pulse oximeters—why they are biased and what technological fixes might be possible.

To understand the problem, you first have to understand how pulse oximeters work. Most of these devices clamp onto some part of the body—usually a fingertip, but sometimes they need to be placed on earlobes or toes. One side of the clamp contains LEDs that emit light in two different wavelengths—red and infrared. A sensor on the other side of the clamp measures how much of that light passes through the tissue. The hemoglobin in oxygenated blood and deoxygenated blood absorbs these wavelengths differently, and by calculating the ratio of the red-light measurements to the infrared-light measurements—the R value—the device can tabulate blood oxygen saturation.

Here’s the problem: other factors can affect how much light is absorbed. Dark nail polish, for example, can throw off the reading. Or tattoos. Or melanin. “If a person has a darker skin tone, they’re going to be absorbing more light,” says Maggie Delano, an engineer at Swarthmore College who is interested in inclusive engineering design. Imagine there are 100 photons of light going through a finger. Some get absorbed by blood, some by bone, and some by melanin in the skin. “So if someone has a darker skin tone, maybe five photons get through instead of 20,” Delano says. “If your electronics don’t compensate for that in some way, there can be errors in that result.”

Those errors can have real clinical consequences. Blood oxygen is one of the key vital signs doctors use to determine whether someone needs to receive oxygen or be admitted to the hospital.   

Engineers are working to fix this problem in a variety of ways. At Tufts, Valencia Koomson and her colleagues have developed a device that can detect when the signal quality is poor or when the user has a darker skin tone and compensate by sending more light through. “We’re dealing with very weak optical signals that have to transverse through tissues with lots of [other] elements that absorb and scatter light,” she told Inverse. “It’s very similar to when you’re riding a car and you go through a tunnel. You lose signal because of the absorption of the materials in the tunnel, such that the signal being transmitted from the cell-phone tower is too weak to be processed by your phone.”

Koomson and her colleagues are collaborating with a medical-device manufacturing company to develop a prototype for clinical trials. Because their team was named a finalist in a recent challenge by Open Oximetry, they’ll be able to validate the device for free in the Hypoxia Lab at the University of California, San Francisco.

Meanwhile, engineers at Brown University are trying to find a workaround using special LEDs that can emit polarized light beams. Jesse Jokerst, an engineer at the University of California, San Diego, is working on an oximeter that uses light and sound, and also corrects for skin tone. Another team at the University of Texas at Arlington is hoping to swap the standard red light in pulse oximeters for green light, which bounces back instead of being absorbed. At Johns Hopkins, engineers have developed a prototype pulse oximeter that factors in skin tone when calculating blood oxygen saturation.

Neal Patwari, a mechanical engineer at Washington University in St. Louis, wants to keep the pulse oximeter’s hardware the same, but swap out the algorithm. A pulse oximeter takes four different measurements, two in each wavelength. One measurement takes place as the heart pushes blood through the arteries, when blood flow is at a maximum, and the other happens between pulses, when blood flow is at a minimum. Those four numbers get fed into an algorithm that calculates ratios—actually, one ratio divided by another. That gives you the R value. But, “when you take two numbers and divide them, you can get some strange effects when the denominator is noisy,” Patwari says. And one of the factors that can increase noisiness is darkly pigmented skin. He hopes to find an algorithm that doesn’t rely on ratios, which could offer up a less biased R value. 

Whether any of these strategies will fix the bias in pulse oximeters remains to be seen. But it’s likely that by the time improved devices are up for regulatory approval, the bar for performance will be higher. At the meeting last week, committee members reviewed a proposal that would require companies to test the device in at least 24 people whose skin tones span the entirety of a 10-shade scale. The current requirement is that the trial must include 10 people, two of whom have “darkly pigmented” skin.

In the meantime, health-care workers are grappling with how to use the existing tools and whether to trust them. In the advisory committee meeting on Friday, one committee member asked a representative from Medtronic, one of the largest providers of pulse oximeters, if the company had considered a voluntary recall of its devices. “We believe with 100% certainty that our devices conform to current FDA standards,” said Sam Ajizian, Medtronic’s chief medical officer of patient monitoring. A recall “would undermine public safety because this is a foundational device in operating rooms and ICUs, ERs, and ambulances and everywhere.”

But not everyone agrees that the benefits outweigh the harms. Last fall, a community health center in Oakland California, filed a lawsuit against some of the largest manufacturers and sellers of pulse oximeters, asking the court to prohibit sale of the devices in California until the readings are proved accurate for people with dark skin, or until the devices carry a warning label.

“The pulse oximeter is an example of the tragic harm that occurs when the nation’s health-care industry and the regulatory agencies that oversee it prioritize white health over the realities of non-white patients,” said Noha Aboelata, CEO of Roots Community Health Center, in a statement. “The story of the making, marketing and use of racially biased pulse oximeters is an indictment of our health-care system.”

Read more from MIT Technology Review’s archive

Melissa Heikkilä’s reporting showed her just how “pale, male, and stale” the humans of AI are. Could we just ask it to do better? 

No surprise that technology perpetuates racism, wrote Charlton McIlwain in 2020. That’s the way it was designed. “The question we have to confront is whether we will continue to design and deploy tools that serve the interests of racism and white supremacy.”

We’ve seen that deep-learning models can perform as well as medical professionals when it comes to imaging tasks, but they can also perpetuate biases. Some researchers say the way to fix the problem is to stop training algorithms to match the experts, reported Karen Hao in 2021. 

From around the web

The high lead levels found in applesauce pouches came from a single cinnamon processing plant in Ecuador. (NBC)

Alternating arms for your covid vaccines might offer an immunity boost over sticking to the same arm, according to a new study. (NYT)

Weight loss through either surgery or medication lowers blood pressure, according to new research. (CNN)

Pharma is increasingly building AI into its businesses, but don’t expect that to lead to instantaneous breakthroughs. (STAT)

How wastewater could offer an early warning system for measles

Measles is back with a vengeance. In the UK, where only 85% of school-age children have received two doses of the MMR vaccine, as many as 300 people have contracted the disease since October. And in the US, an outbreak has infected nine people in Philadelphia since last month. One case has been reported in Atlanta, another in Delaware. An entire family of six is infected in Washington state. 

On January 23, the World Health Organization issued a warning. “It is vital that all countries are prepared to rapidly detect and timely respond to measles outbreaks, which could endanger progress towards measles elimination,” said Hans Kluge, WHO regional director for Europe. 

Catching measles outbreaks early is tricky, though. Like many other respiratory viruses, it starts off with a cough, runny nose, fever, and achy body. The telltale rash doesn’t appear for two to four more days. By then, a person is already infectious. Very infectious, in fact. Measles is one of the most contagious diseases around.

Maybe there’s a solution. The US developed a vast wastewater sampling network to detect covid during the pandemic. Could we leverage that network to provide an early warning system for measles?

“I actually think you could make the argument that measles is even more important to [detect] than covid or influenza or any of the other pathogens that we’re looking for,” says Samuel Scarpino, an epidemiologist at Northeastern University in Boston.

Wastewater surveillance relies on standard lab tests to find genetic evidence of pathogens in sewage—DNA or RNA. When people are infected with covid, they shed SARS-CoV-2 in their stools, so it’s easy to see why it would show up in wastewater. But even viruses that don’t get pooped out can show up in the sewers. 

Although measles is a respiratory virus, people shed it in their urine. They also brush their teeth and spit in the sink. They blow their noses and throw the tissue in the toilet. “We shed these viruses and we shed bacteria and fungi in so many ways that end up in the sewer,” says Marlene Wolfe, an environmental microbiologist and epidemiologist at Emory University and one of the directors of WastewaterSCAN, a program based at Stanford that monitors infectious diseases through municipal wastewater systems. 

The literature on wastewater detection of measles is scant, but encouraging. In one study, a team of researchers in the Netherlands tested wastewater samples collected in 2013 during a measles outbreak in an orthodox Protestant community for evidence of the virus. They found measles RNA, and the positive samples matched the locations where cases had been reported. They even managed to confirm that the virus in one sample was genetically identical to the outbreak strain. But not every measles case showed up in the sewers. Some samples taken where cases had occurred didn’t harbor any measles RNA. 

In another study, researchers from Nova Scotia developed a tool to screen wastewater for four pathogens simultaneously: RSV, influenza, covid, and measles. When they tested it in Nova Scotia, they didn’t get any positive hits for measles, which didn’t surprise them as no cases had been reported. But when they seeded the wastewater samples with a surrogate for measles, they were able to detect it at both high and low concentrations

The real question, Wolfe says, is whether detecting measles in wastewater would have any public health value. Because measles is rarely asymptomatic and the rash is so distinctive, cases tend to get noticed. “Some of our other systems can work pretty well at identifying measles cases as they come up,” she says.

Wolfe could see value in monitoring, she says, if people really shed high quantities of the virus before those signs are visible. “Then it really could provide an early warning,” she says. But that’s not known at the moment. 

What would a wastewater surveillance program for measles look like? “If we had the ability to target places where the vaccination coverage was lower, that would be a place to prioritize resources,” Scarpino says. “Airports and other ports of entry are going to be really important as well.” Earlier this month, someone infected with measles passed through both Dulles and Ronald Reagan airports just outside of Washington, DC. Finding measles RNA in airport sewage doesn’t necessarily mean a local outbreak might occur, but “it definitely means that the risk profile is there and we should be monitoring much more actively,” he says. 

While measles isn’t part of wastewater surveillance yet, plenty of other pathogens are. Health officials around the globe have been testing sewage for polio since the late 1980s. Because people who contract polio shed large amounts of the virus in their feces, and because so many people are asymptomatic, “it’s like a perfect use case in a lot of ways,” Wolfe says. But wastewater surveillance didn’t really become fashionable until 2020, when covid hit. 

The National Wastewater Surveillance System, which the Centers for Disease Control and Prevention (CDC) launched in 2020 to monitor covid, now also tests for mpox. WastewaterSCAN currently tests for 10 different pathogens, including covid, mpox, RSV, influenza, norovirus, and rotavirus. The team publishes that data on a dashboard on its website and shares it with the CDC. Wolfe and her colleagues also recently worked with Miami-Dade County in Florida to assess the feasibility of testing for dengue. Even though dengue is rare in Florida, the team picked up a signal in the wastewater. 

In fact, wastewater surveillance works for most of the pathogens they’ve tried, Wolfe says: “The potential for leveraging this tool to effectively support measles surveillance is absolutely possible.” 

Another thing

The complement system may be the most important immune defense you’ve never heard of. And now two teams of researchers say that this microbe-fighting protein cascade is abnormal in some people with long covid, pointing researchers toward new potential therapies. 

Read more from MIT Technology Review’s archive

Wastewater with its wealth of microbes could help researchers track the evolution of antibiotic resistance in bacteria, Jessica Hamzelou wrote last year. 

Health officials used wastewater surveillance to track the spread of mpox in 2022 and helped scientists estimate how many people in California’s Bay Area might be affected, Hana Kiros reported. 

Way back in 2021, Antonio Regalado covered some of the first efforts to track the spread of covid variants using wastewater.  

From around the web

The FDA slapped a black box warning on CAR-T cancer therapies, which rely on engineered T cells to fight the disease. The decision comes after the agency received 25 reports of new blood cancers in people who received these treatments. (NBC)

My latest for Nature is a deep dive into efforts to restore immune tolerance in people with autoimmune diseases. Researchers are finally having some success addressing the cause of these diseases and are even talking about (gasp!) the possibility of a cure. (Nature)   

An 11-year-old boy who was born deaf can now hear after receiving gene therapy as part of a clinical trial. “There’s no sound I don’t like,” he told the New York Times. “They’re all good.” (NYT)

Donated bodies are powering gene-edited organ research

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Hooked up to a ventilation machine, a person can be dead in the eyes of the law, medical professionals, and loved ones, yet still alive enough to be useful for medical research. Such brain-dead people are often used for organ donation, but they are also of increasing importance to the biotech world. 

This week, we reported how surgeons at the University of Pennsylvania connected a pig liver to a brain-dead person in an experiment that lasted for three days.

The point was to determine whether the organ—which was mounted inside a special pumping device—could still do its job of cleaning up toxins from the body, and possibly lead to a new approach for helping patients with acute liver failure.

Using entire bodies in this way—as an experimental “decedent model”—remains highly unusual. But there’s been an upsurge in requests for bodies as more companies start testing animal-to-human organ transplants using tissues from specially gene-edited pigs.

“In order to get to humans, you have to go through steps. You can’t say ‘I am going to try it tomorrow,’ as you did 50 years ago,” says Abraham Shaked, the surgeon at Penn who directed the experiment.

To learn how common it is to use bodies as experimental models, I checked in with Richard Hasz, CEO of Gift of Life Donor Program, a nonprofit that arranges for organ donation in Pennsylvania, New Jersey and Delaware, and which provided Penn with the body used in the liver experiment.

“It’s definitely a new model. But sometimes we repeat things that have happened before. We have been around 50 years, and this is the second time it’s been requested,” says Hasz.

The previous time was in the 1980s, when researchers at Temple University sought out brain-dead bodies as a “no risk” way to test an early artificial heart made from plastic and metal. They wanted to see how it fit in a chest and test surgical techniques before trying the mechanical heart in a living patient.

Starting in 2021, though, donation organizations again started hearing from surgeons who needed brain-dead people, sometimes called “beating-heart cadavers.”  That was because several companies had developed gene-edited pigs and doctors were ready to start trying their organs.

According to a tally from the biotech company eGenesis, of the 10 pig-to-human transplant experiments that have taken place in the US since 2021, two have been in living people, but the other eight have involved brain-dead bodies.

The main use of such bodies is as organ donors. Although most people don’t realize it, says Hasz, only that relatively rare 1% to 2% of people who experience brain death while under medical care can have their organs collected.

“It’s a big misconception that anyone who has died in a car accident or outside the hospital can be an organ donor. You have to have died in the ICU from a devastating neurological injury to your brain,” he says.

It’s that brain-dead but beating-heart state that provides the time—sometimes a day or two—to move the body to a central location, find a suitable recipient, and allow surgeons to remove the organs.

Organizations like Hasz’s are the ones that approach families, transport the bodies, and help match organs to recipients.  Last year Gift of Life helped arrange for 1,734 transplants of organs taken from 693 donors.

The family of the patient in this case—really, the “decedent,” since he’d been declared brain dead—wanted to see his organs donated. But there weren’t any takers; sometimes factors like cancer, age, or infections make organs less desirable.

So Hasz approached the family about another option. Would they agree to let his body be used in an experiment with a pig liver?  The whole concept was new to them, but they quickly agreed, he says.

“Our team tried to shepherd this family to understand all the ins and outs of what that would mean—the length of time, the goals, the fact that it would be an extracorporeal support—and provide them with all that information,” he says.

This time the experiment lasted only 72 hours, as that’s about how long a pig liver would be needed to support a real patient. Hasz says other families might be comfortable with longer experiments, but probably not anything indefinite: “We can maintain a body with mechanical support once they are declared medically and legally dead, but families have a desire for closure, funeral services, and depending on the family, they may limit it to one day or one month.”

Hasz says his team will be looking for more body donors to support further experiments with pig livers. And he expects many will agree. “We depend every day in organ transplant on the kindness of strangers who are at their worst possible moment, but they can set that aside and think of others,” he says. “Having talked to many families over the years, I am always surprised and humbled by their willingness to say yes.”

Read more from MIT Technology Review’s archive

Last year, MIT Technology Review’s Mortality Issue explored how technology is sometimes blurring the line between life and death. News editor Charlotte Jee wrote my favorite story in the issue, which described how chatbots can create  “digital clones” that let people speak to their dead relatives.

We said donated organs only come from brain-dead individuals. But there are some exceptions. In 2015 we wrote about a device that could revive hearts that had stopped beating, making them available for transplant.

Pig-to-human organ transplants made our 2023 list of 10 Breakthrough Technologies because they could end the organ shortage. We took a deep dive into one entrepreneur’s plans to make it happen.

Around the web

A lab in China reported experiments with a coronavirus that is 100% fatal to mice and could harm humans. It caused brain damage and turned their eyes white. Some scientists condemned the risky research as “madness.” (New York Post)

Perverse incentives, no real negotiation, and profiteering middlemen. Those are among the five key reasons drug prices in the US are nearly twice those in some European countries. (New York Times)

No one can resist a cute animal story—I think that’s why efforts to test anti-aging drugs in pets get so much media attention. But now people are howling about the $7-million-a-year Dog Aging Project, whose organizers say they’re about to lose their government funding. The project has been testing the life-span effects on dogs of a drug called rapamycin. (Science)

These AI-powered apps can hear the cause of a cough

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

This week I came across a paper that uses AI in a way that I hadn’t heard of before. Researchers developed a smartphone app that can distinguish tuberculosis from other diseases by the sound of the patient’s cough.

The method isn’t foolproof. The app failed to detect TB in about 30% of people who actually had the disease. But it’s simpler and vastly cheaper than collecting phlegm to look for the bacterium that causes the disease, the gold-standard method for diagnosing TB. So it could prove especially useful in low-income countries as a screening tool, helping to catch cases and interrupting transmission.

In the new study, a team of researchers from the US and Kenya trained and tested their smartphone-based diagnostic tool on recordings of coughs collected in a Kenyan health-care center—about 33,000 spontaneous coughs and 1,200 forced coughs from 149 people with TB and 46 people with other respiratory conditions. The app’s performance wasn’t good enough to replace traditional diagnostics. But it could be used as an additional screening tool. The sooner people with active cases of TB are identified and receive treatment, the less likely they will be to spread the disease. 

This new paper is one of dozens that have come out in recent years that aim to use coughs and other body sounds as “acoustic biomarkers”—sounds that indicate changes in health.  The concept has been around for at least three decades, but in the past five years, the field has exploded. What changed, says Yael Bensoussan, a laryngologist at the University of South Florida, is the growing use of AI: “With artificial intelligence, you can analyze a larger quantity of data faster.”

Covid also helped drive interest in cough analysis. The pandemic gave rise to 30 or 40 startups focusing on the acoustics of cough, Bensoussan says. AudibleHealthAI launched in 2020 and began working on a mobile app designed to diagnose covid. The software, called AudibleHealth DX, is currently being reviewed by the FDA. And now the company is now branching out to influenza and TB.

The Australian company ResApp Health has been working on acoustic diagnosis of respiratory diseases since 2014, well before the pandemic. But when covid emerged, the company pivoted and developed an audio-based covid-19 screening test. In 2022, the company announced that the tool correctly identified 92% of positive covid cases just from the sound of a patient’s cough.  Soon after, Pfizer paid $179 million to acquire ResApp.

Bensoussan is skeptical that these kinds of apps will become reliable diagnostics. But she says apps that detect coughs—any coughs—could prove to be  valuable health tools even if they can’t pinpoint the cause. Coughs are especially easy for smartphones to capture. “It’s a sea change to have a common device, the smartphone, which everyone has sitting by their bedside or in their pocket to help observe your coughs,” Jamie Rogers, product manager at Google Health, told Time magazine. Google’s newest Pixel phones have cough and snore detection available.

Bensoussan also thinks cough-tracking apps could be game-changers for clinical trials where coughs are one of the things researchers are trying to measure. “It’s really hard to track cough,” she says. Researchers often rely on patients’ recall of their coughing. But an app would be far more accurate. “It’s really easy to capture the frequency of cough from a tech perspective,” she says. 

And it’s not just coughs that can reveal clues about our health status. Bensoussan is leading a $14 million project funded by the NIH to develop a massive database of voice, cough, and respiratory sounds to aid in the development of tools to diagnose cancers, respiratory illnesses, neurological and mood disorders, speech disorders, and more. The database captures a wide variety of sounds—coughing, reading sentences or vowel sounds, inhaling, exhaling, and more. 

“One of the big limitations is that a lot of these studies have private data sets that are secret,” Bensoussan says. That makes it difficult to validate the research. The database that she and her colleagues are developing will be publicly available. She expects the first data release to happen before June.

As more data becomes available, expect to see even more apps that can help alert us to health problems on the basis of cough or speech patterns. It’s too soon to say whether those apps will make a significant difference in diagnosis or screening,  but we’ll keep an ear out for any new developments.  

Read more from MIT Technology Review’s archive

Vocal cues could provide a way to diagnose PTSD, traumatic brain injuries, mood disorders, and even heart disease, Emily Mullin wrote in this story from 2017. 

AI tools might perform well  in the lab but falter in the chaos of the real world. Will Douglas Heaven unpacked what happened when Google Health implemented a tool in Thailand to screen people for an eye condition linked to diabetes. 

In a previous issue of The Checkup, Jessica Hamelzou outlined why we shouldn’t let AI make all our health-care decisions: “Doctors may be inclined to trust AI at the expense of a patient’s own lived experiences, as well as their own clinical judgment.” 

From around the web

Safe bathrooms equipped with motion sensors have eliminated overdose deaths at a Boston clinic that serves unhoused individuals in the city’s infamous “methadone mile”—further proof that supervised consumption sites would save lives. (STAT)

Now that we’ve got new blockbuster weight-loss drugs, some companies are looking to develop longer-lasting treatments and preventatives. But some say an obesity-free future won’t come from pharma. “We are not going to be able to treat our way out of this problem, or medicalize our way out of this problem,” says William Dietz, director of the Global Center for Prevention and Wellness at George Washington University. “What we need to do is to come to terms with the kind of environmental forces which are driving obesity, and generate the political will necessary to address those factors.” (STAT) 

Advances in neuroscience have sparked worries that brain-computer interfaces might someday read people’s minds or hamper free will. Now “neurorights” advocates are racing against the clock to push for laws that would protect against the misuse and abuse of neurotechnology. (Undark)

Gene editing had a banner year in 2023

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Welcome back to The Checkup. This will be our last issue of 2023, so this week I’ve been reflecting on our biotechnology coverage over the past year. As I scrolled through our archives, I was struck by the vast number of stories we wrote about gene editing.

It really shouldn’t have come as a surprise. Perhaps no technology has more power to transform medicine, and its vast potential is just beginning to be realized. Gene editing can be used to delete, insert, or alter portions of our genetic code. We’ve been able to modify DNA for years, but newer technologies like CRISPR mean that we can do it faster, more accurately, and more efficiently than ever before. In 2023, we saw the first approval of a CRISPR-based gene-editing therapy. And many more are to come. So let’s take a look at the developments that made news this year. What is the promise of gene editing, and what are the current pitfalls?

Lucky breaks and next steps 

Casgevy, the first CRISPR therapy, has already been approved in the UK and US to treat sickle-cell disease. And it’s now on the cusp of approval in the European Union. Sickle-cell disease is caused by a mutation in the hemoglobin gene that leads to a characteristic crescent moon shape of the red blood cells. The treatment doesn’t address the underlying cause of the disease; instead, it disables another gene, one that hampers production of a type of hemoglobin that people normally produce only in the womb and as babies. With that gene out of commission, production of this second type of hemoglobin resumes. The therapy works because cells with fetal hemoglobin won’t form sickles. You can read more about the fascinating backstory on the development of Casgevy in this story by my colleague Antonio Regalado. 

Why go at it in this roundabout way? Current versions of CRISPR work best as a pair of scissors, creating snips that disable genes. That limits its usefulness. New versions of CRISPR will allow researchers to alter the genetic code or even insert new genes, which will make it possible to address a wide variety of genetic diseases.

Verve Therapeutics, for example, is testing an approach called base editing. Jessica Hamzelou covered this technique in depth in this story in January: “There are four DNA bases: A, T, C, and G. Instead of cutting the DNA, CRISPR 2.0 machinery can convert one base letter into another. Base editing can swap a C for a T, or an A for a G.” According to Kiran Musunuru, cofounder and senior scientific advisor at Verve, “It’s no longer acting like scissors, but more like a pencil and eraser.”

Verve’s therapy, now being tested in a small clinical trial, swaps out a single base in a gene for a protein called PCSK9, which is linked to high cholesterol. (The therapy was one of MIT Technology Review’s 10 Breakthrough Technologies 2023.) That change disables the gene, which means that the body makes less PCSK9 and cholesterol levels fall. In November the company announced interim results: a single injection of the therapy reduced LDL levels in the blood by up to 55% in 10 people with a genetic condition that causes high cholesterol.

CRISPR 3.0, which allows scientists to replace bits of DNA or insert new chunks of genetic code, is still being tested in animals. One company, Prime Medicine, plans to seek FDA approval to launch a human trial of a treatment for chronic granulomatous disease, a genetic immune disorder, in 2024 .

Pitfalls remain, at least for now. 

The only approved CRISPR therapy isn’t a simple fix. Patients have to undergo a bone-marrow transplant: after chemotherapy to destroy their faulty cells, stem cells are extracted, edited in the lab, and then reinfused. Jimi Olaghere, one of the few people to have received the therapy, wrote about how arduous this was. The cell collection process left him so weak he needed blood transfusions. And the chemo meant “dealing with nausea, weakness, hair loss, debilitating mouth sores, and the risk of exacerbating the underlying condition.” All told, he spent 17 weeks in the hospital.

Given the complexity of the treatment, you won’t be surprised to learn that it’s expensive—it costs an estimated $2.2 million. That price tag means it’s out of reach for many, especially people in low-income countries.

Vertex is already exploring strategies to make sickle-cell therapies more accessible and affordable. Antonio spoke to the company’s head of research, David Altshuler, about some of the strategies earlier this month.  One of the more promising approaches might not involve gene editing at all.

“One question I get a lot is: How are we going to get to the rest of the world?” Altshuler said. “And I think the answer is not by trying to do bone-marrow transplants in the rest of the world. It’s just too resource intensive, and the infrastructure is not there. I think the goal will be achieved sooner by finding another modality, like a pill that can be distributed much more effectively.”

Safety concerns abound. Gene editing is permanent, and one of the biggest concerns is that these therapies might miss the mark and create “off-target” effects. Regulators were so concerned about this possibility that an FDA advisory committee met in November to assess whether Vertex would need to provide additional data to prove Casgevy’s safety. (They ultimately decided the existing data was sufficient for approval.) The company plans to follow up with patients for 15 years to confirm safety.

Most experts think base editing, which doesn’t involve snipping, should be safer than the CRISPR scissors. But even there, safety has been front and center in discussions. The positive results in Verve’s trial of base editing to treat high cholesterol were partly overshadowed by the fact that two participants had heart attacks, and one of them died.

The epic patent dispute over CRISPR has long been another potential hiccup for possible therapies. But this month Antonio reported on a partial resolution. Vertex agreed to pay tens of millions of dollars to competitor Editas and the Broad Institute for the right to use Broad’s CRISPR patent, thus avoiding a potential lawsuit. “It’s not yet clear if the license agreement points to an end of the fierce patent fight between Broad and Berkeley. That has been continuing before a US patent court, with Berkeley still trying to overturn its rival’s claims,” he wrote.

Despite the pitfalls, it’s clear that gene-editing therapies, when they work, can be transformational. Olaghere detailed his experience as a trial participant.  “I started to experience things I had only dreamed of: boundless energy and the ability to recover by merely sleeping. My physical symptoms—including a yellowish tint in my eyes caused by the rapid breakdown of malfunctioning red blood cells—virtually disappeared overnight,” he wrote. “Most significantly, I gained the confidence that sickle-cell disease won’t take me away from my family, and a sense of control over my own destiny.”

Another thing

• Hunter-gatherer societies may still retain many of the microbes that people living in industrialized societies lack. That’s why scientists are racing to catalog their microbiome. But there’s a catch, writes senior reporter Jessica Hamzelou. “We don’t know whether those in hunter-gatherer societies really do have ‘healthier’ microbiomes—and if they do, whether the benefits could be shared with others.” What’s more, members of these communities say some research is being conducted without regard for ethics or equity. “Taking advantage of an Indigenous population and using their microbes to try to reinstate health in somebody from a wealthy, industrialized nation, I think, is a problematic thing to do,” Justin Sonnenburg, a microbiome scientist at Stanford University, told her.

From around the web

• A New York Times investigation delves into the increasingly popular practice of snipping “tongue-ties” in babies, an often unnecessary procedure being aggressively pushed by some lactation consultants and dentists. A heartbreaking must-read. (NYT)
• Studies call into question the benefit of spinal cord stimulation for pain (Medpage) 
• Researchers are testing a new non-hormonal male birth control pill in a clinical trial in the UK.. (Stat)
• Chemotherapy drug shortages are robbing cancer patients of the therapies they desperately need and highlighting systemic problems in the generic drug market. (NYT) But there are some possible fixes. (NYT)
• The high lead levels in some applesauce pouches, which sickened more than 100 children in the US, came from the cinnamon that was added. Regulators are still trying to work out why the cinnamon contained lead. (Washington Post)

The first CRISPR cure might kickstart the next big patent battle

That’s a real nice CRISPR cure you have there. It would be a pity if anything happened to it. 

Okay. Drop the tough-guy accent and toss the black fedora aside. But I do believe that similar conversations could be occurring now that a historic gene-editing cure is coming to market, as soon as this year.

By the middle of December, Vertex Pharmaceuticals, based in Boston, is expected to receive FDA approval to sell a revolutionary new treatment for sickle-cell disease that’s the first to use CRISPR to alter the DNA inside human cells. (Vertex has already received regulatory approval in the UK.)

The problem is that the US patent on editing human cells with CRISPR isn’t owned by Vertex—it is owned by the Broad Institute of MIT and Harvard, probably America’s largest gene research center, and exclusively licensed to a Vertex competitor, Editas Medicine, which has its own sickle-cell treatment in testing.

That means Editas will want Vertex to pay. And if it doesn’t, Broad and Editas could go to the courts to claim patent infringement, demand royalties and damages, or even try to stop the treatment from being sold with an injunction.

“I imagine we’ll see a lawsuit by the end of the year,” says Jacob Sherkow, an expert on gene-editing patents at the University of Illinois College of Law. “It’s the moment patent litigators in this space have been waiting for.”

Now for some disclaimers. Yes, I work for MIT. No, I don’t benefit directly from the CRISPR patents. But others around here do. I recently talked to a scientist who, despite having only a secondary role in some follow-up CRISPR research, told me they have been receiving yearly royalty checks sometimes equaling their salary.

Back in 2014, MIT Technology Review broke the story of the infamous battle to control the patents on CRISPR—and almost a decade later the dispute remains one of the foundational narratives around the genetic super-tool, which can be programmed to cut DNA at precise locations. 

The dispute pitted Broad Institute gene whiz Feng Zhang against the researchers who eventually earned the Nobel for developing CRISPR editing: Jennifer Doudna of the University of California, Berkeley, and Emmanuelle Charpentier, now with the Max Planck Institute in Germany.

Doudna and Charpentier might have the Nobel, but Zhang’s head-turning claim that he was the real inventor of CRISPR genome editing has so far won out in the US, despite vigorous and ongoing efforts by Berkeley at appeals. Although Broad’s intellectual property quest got little result in Europe, its CRISPR patent still reigns supreme here, in the world’s biggest drug market. 

And really, what’s the point of such a hard-won triumph unless it’s to enforce your rights? “Honestly, this train has been coming down the track since at least 2014, if not earlier. We’re at the collision point. I struggle to imagine there’s going to be a diversion,” says Sherkow. “Brace for impact.”

The Broad Institute didn’t answer any of my questions, and a spokesperson for MIT didn’t even reply to my email. That’s not a surprise. Private universities can be exceedingly obtuse when it comes to acknowledging their commercial activities. They are supposed to be centers of free inquiry and humanitarian intentions, so if employees get rich from biotechnology—and they do—they try to do it discreetly.

There are also strong reasons not to sue. Suing could make a nonprofit like the Broad Institute look bad. Really bad. That’s because it could get in the way of cures.

“It seems unlikely and undesirable, [as] legal challenges at this late date would delay saving patients,” says George Church, a Harvard professor and one of the original scientific founders of Editas, though he’s no longer closely involved with the company.  

If a patent infringement lawsuit does get filed, it will happen sometime after Vertex notifies regulators it’s starting to sell the treatment. “That’s the starting gun,” says Sherkow. “There are no hypothetical lawsuits in the patent system, so one must wait until it’s sufficiently clear that an act of infringement is about to occur.”

How much money is at stake? It remains unclear what the demand for the Vertex treatment will be, but it could eventually prove a blockbuster. There are about 20,000 people with severe sickle-cell in the US who might benefit. And assuming a price of $3 million (my educated guess), that’s a total potential market of around $60 billion. A patent holder could potentially demand 10% of the take, or more.

Vertex can certainly defend itself. It’s a big, rich company, and through its partnership with the Swiss firm CRISPR Therapeutics, a biotech co-founded by Charpentier, Vertex has access to the competing set of intellectual-property claims—including those of UC Berkeley, which (though bested by Broad in the US) hold force in Europe and could be used to throw up a thicket of counterarguments.

Vertex could also choose to pay royalties. To do that, it would have to approach Editas, the biotech cofounded by Zhang and Church in Cambridge, Massachusetts, which previously bought exclusive rights to the Broad patents on CRISPR in the arena of human treatments, including sickle-cell therapies.

It’s pretty clear Editas would like to ink a deal. On November 14, at a meeting with stock analysts, Editas CFO Erick Lucera said his company has at least two people working pretty much full time making calls and trying to get other companies developing CRISPR treatments to pay up. Indeed, he said, cashing in on the patents and bringing in revenue from them is a “pillar” of the Editas business model.

“I think there’s a lot of companies that probably are going to have to have a conversation with us about using our license from a freedom-to-operate standpoint, and we are open to those discussions,” Lucera told analysts. “We’re not talking about any particular licenses until they’re signed … But I think you all know the companies that are out there.”

You know who you are, Vertex Pharmaceuticals. Tug the fedora for emphasis.

When I contacted Vertex, and later CRISPR Therapeutics, spokespeople at both companies sent me identical replies: “I won’t have anything to say about CRISPR patents.” Okay, then. Maybe a deal is already in the works. 

One final thought. If you were to discover a super-technique like CRISPR, it might be smarter to sell non-exclusive rights to all comers. Let a thousand flowers bloom. But that isn’t what happened. Instead, universities sold exclusives to develop CRISPR drugs to startups founded by their own researchers. Thus they planted the seeds of incurable dispute.

On its website, the Broad Institute explains why they did it. It says: “Exclusivity is necessary to drive the level of investment needed to develop certain technologies to the point that they are safe, effective, and capable of precise editing in specific cell types.”

Broad is correct that the CRISPR exclusive to Editas brought investment into that company, but a share of it was then used to fund the CRISPR patent fight. In fact, Editas financial reports indicate the company has been spending roughly $10 million on it per year. 

So now, after spending that kind of money, its investors would be absolutely right to demand a return—with a lawsuit if necessary.

“That can be considered the initial sin,” says Ulrich Storz, a patent attorney in Germany who recently wrote a detailed review of the CRISPR situation for the Journal of Biotechnology. “Of course a company wants exclusivity. But why did the university play that game?”

The pain is real. The painkillers are virtual reality.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

I hate needles. I am a grown woman who owns a Buzzy, a vibrating, bee-shaped device you press against your arm to confuse your nerves and thus reduce pain during blood draws. I once was so anxious a nurse gave me a n iPad so I could watch Moana while getting blood taken.

That’s why I was so excited to read about Smileyscope, a VR device for kids that recently received FDA clearance. It helps lessen the pain of a blood draw or IV insertion by sending the user on an underwater adventure that begins with a welcome from an animated character called Poggles the Penguin. Inside this watery deep-sea reality, the cool swipe of an alcohol wipe becomes cool waves washing over the arm. The pinch of the needle becomes a gentle fish nibble.  

Studies suggest the device works. In two clinical trials that included more than 200 children aged 4 to 11, the Smileyscope reduced self-reported pain levels by up to 60% and anxiety levelsby up to 40%.

But how Smileyscope works is not entirely clear. It’s more complex than just distraction. Back in the 1960s, Ronald Melzack and Patrick Wall posited that pain signals travel through a series of “gates” in the spinal cord that allow some to reach the brain and keep others out. When the brain is occupied by other stimuli, the gates close and fewer pain signals can get through. “And that’s the mechanism of action for virtual reality,” says Paul Leong, chief medical officer and co-founder of Smileyscope.

Not all stimuli are equally effective. “[In] traditional virtual reality you put on the headset and you go somewhere like a beach,” Leong says. But that kind of immersive experience has nothing to do with what’s happening in the real world. Smileyscope aims to reframe the stimuli in a positive light. Mood and anxiety can also affect how we process pain. Poggles the Penguin takes kids on a thorough walk-through of a procedure before it begins, which might reduce anxiety. And experiencing an underwater adventure with “surprise visitors” is undoubtedly more of a mood-booster than staring at clinic walls, waiting for a needle prick.

“There are a lot of ways to distract people,” says Beth Darnall, a psychologist and director of the Stanford Pain Relief Innovations Lab. But the way Smileyscope goes about it, she says, is “really powerful.”

Researchers have been working on similar technologies for years. Hunter Hoffman and David Patterson at the University of Washington developed a VR game called SnowWorld over two decades ago to help people with severe burns tolerate wound dressing changes and other painful procedures. “We created a world that was the antithesis of fire,” Hoffman told NPR in 2012, “a cool place, snowmen, pleasant images, just about everything to keep them from thinking about fire.” Other groups are exploring VR for postoperative pain, childbirth, pain associated with dental procedures, and more.

Companies are also working on virtual reality devices that will address a much tougher problem: chronic pain. In 2021 RelieVRx became the first VR therapy authorized by the FDA for pain. (The FDA keeps a list of all authorized VR/AR devices.) The tool aims to teach people how to manage chronic pain, which is entirely different from the temporary sting of a needle stick. “It’s vastly more complex on every level,” says Darnall, who helped develop RelieVRx and now serves as ​​chief science advisor for AppliedVR, which markets the device.

Chronic pain is long term, and often life altering. “You have now literal changes in your nervous system as a consequence of experiencing pain long term,” Darnall says. “You have stored tension, you have maybe persistent anxiety, your activity levels have changed, you have sleep problems.” The alarm bell rings long after the danger has passed, for months, years, or even decades. 

With RelieVRx, the intention isn’t to distract, it’s to teach pain relief strategies that physicians already know work, such as mindfulness, cognitive-behavioral therapy, and relaxation. “We are helping people unlearn some physiologically hardwired pain processes that over time become unhelpful,” Darnell says. “It’s fundamentally skills-based.” Patients use the device six minutes a day for eight weeks, and that seems to be enough for many of them to acquire skills to manage their own pain. At three months, 30% were still experiencing a reduction in pain intensity.  

RelieVRx has another benefit, too: it’s meant for home use. That means people don’t necessarily have to schedule appointments with a therapist to receive behavioral pain treatment, which makes therapy more accessible. “It’s dismantling barriers to this type of effective nonpharmacologic care,” Darnall says. That’s good news for the 50 million people in the US who experience chronic pain that can’t be controlled with medication. It’s one more option for a condition that is notoriously tough to treat.

VR won’t be a panacea for people with chronic pain or for anxious kids who need shots, and it’s not risk-free. It can cause nausea, headaches, and motion sickness. But the technology could prove exceedingly useful for some people. People like me.  

Providing patients with an escape during painful procedures may not seem like a medical necessity. In most cases, the procedure can be performed successfully either way. But pain is powerful, and a patient’s experience can directly influence future interactions with the medical system. “These experiences in childhood are really sentinel to developing behaviors in later life,” Leong says. “Every time you have a needle, that’s an opportunity for something to go well, or terribly. And if it goes terribly, the next time you go back you’re dreading it.”

That dread can have serious ramifications. Maybe you stop going to the clinic, or you avoid getting treatment. In fact, Leong founded Smileyscope because he had a patient with cystic fibrosis who had been so traumatized by the medical procedures he received as a child that he had “disengaged with care,” he says. The man wanted Leong to put him under anesthesia just to have a routine blood draw. “And I just thought, there’s got to be a better way,” he says. 

Now, there just might be. 

Read more from Tech Review’s archive

Long before AppliedVR had a device authorized to address chronic pain, Rachel Metz covered the company’s efforts. 

Could virtual reality “forest bathing” mimic the health impacts of actually spending time in a forest? Some scientists think so, reports Charlie Metcalfe. 

Using virtual reality to relax during surgery may reduce the need for anesthetic. Rhiannon Williams has the story. 

From around the web

Big milestone: The UK has approved the world’s first CRISPR gene editing therapy to treat two blood disorders. (Reuters)

A special gene editing technique called base editing has been used to alter DNA in humans in an attempt to lower cholesterol. Verve Therapeutics presented interim trial results at a meeting of the American Heart Association over the weekend. The data suggest that the therapy holds promise but also raised safety concerns. (Nature) 

Here’s a new worry about ChatGPT: data manipulation. The latest version put together a startlingly accurate fake dataset that made one type of eye surgery appear much more effective than another. (MedPage Today) 

Why high lead levels have been found in pouches of cinnamon applesauce is still a mystery, but the CDC says 22 children have high lead levels in their blood as a result. (CNN)