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)