Mar 30 2024
Brain-cell transplants are the newest experimental epilepsy treatment

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.

Justin Graves was managing a scuba dive shop in Louisville, Kentucky, when he first had a seizure. He was talking to someone and suddenly the words coming out of his mouth weren’t his. Then he passed out. Half a year later he was diagnosed with temporal-lobe epilepsy.

Justin Graves
JUSTIN GRAVES

Graves’s passion was swimming. He’d been on the high school team and had just gotten certified in open-water diving. But he lost all that after his epilepsy diagnosis 17 years ago. “If you have ever had seizures, you are not even supposed to scuba-dive,” Graves says. “It definitely took away the dream job I had.”

You can’t drive a car, either. Graves moved to California and took odd jobs, at hotels and dog kennels. Anywhere on a bus line. For a while, he drank heavily. That made the seizures worse. 

Epilepsy, it’s often said, is a disease that takes people hostage.

So Graves, who is now 39 and two and half years sober, was ready when his doctors suggested he volunteer for an experimental treatment in which he got thousands of lab-made neurons injected into his brain. 

“I said yes, but I don’t think I understood the magnitude of it,” he says. 

The treatment, developed by Neurona Therapeutics, is shaping up as a breakthrough for stem-cell technology. That’s the idea of using embryonic human cells, or cells converted to an embryonic-like state, to manufacture young, healthy tissue.

And stem cells could badly use a win. There are plenty of shady health clinics that say stem cells will cure anything, and many people who believe it. In reality, though, turning these cells into cures has been a slow-moving research project that, so far, hasn’t resulted in any approved medicines.

But that could change, given the remarkable early results of Neurona’s tests on the first five volunteers. Of those, four, including Graves, are reporting that their seizures have decreased by 80% and more. There are also improvements in cognitive tests. People with epilepsy have a hard time remembering things, but some of the volunteers can now recall an entire series of pictures.

“It’s early, but it could be restorative,” says Cory Nicholas, a former laboratory scientist who is the CEO of Neurona. “I call it activity balancing and repair.”

Starting with a supply of stem cells originally taken from a human embryo created via IVF, Neurona grows “inhibitory interneurons.” The job of these neurons is to quell brain activity—they tell other cells to reduce their electrical activity by secreting a chemical called GABA.

Graves got his transplant in July. He was wheeled into an MRI machine at the University of California, San Diego. There, surgeon Sharona Ben-Haim watched on a screen as she guided a ceramic needle into his hippocampus, dropping off the thousands of the inhibitory cells. The bet was that these would start forming connections and dampen the tsunami of misfires that cause epileptic seizures.

Ben-Haim says it’s a big change from the surgeries she performs most often. Usually, for bad cases of epilepsy, she is trying to find and destroy the “focus” of misbehaving cells causing seizures. She will cut out part of the temporal lobe or use a laser to destroy smaller spots. While this kind of surgery can stop seizures permanently, it comes with the risk of “major cognitive consequences.” People can lose memories, or even their vision. 

That’s why Ben-Haim thinks cell therapy could be a fundamental advance. “The concept that we can offer a definitive treatment for a patient without destroying underlying tissue would be potentially a huge paradigm shift in how we treat epilepsy,” she says. 

Nicholas, Neurona’s CEO, is blunter. “The current standard of care is medieval,” he says. “You are chopping out part of the brain.”

For Graves, the cell transplant seems to be working. He hasn’t had any of the scary “grand mal” attacks, that kind can knock you out, since he stopped drinking. But before the procedure in San Diego, he was still having one or two smaller seizures a day. These episodes, which feel like euphoria or déjà vu, or an absent blank stare, would last as long as half a minute. 

Now, in a diary he keeps as part of the study to count his seizures, most days Graves circles “none.”

LUIS FUENTEALBA AND DANIEL CHERKOWSKY

Other patients in the study are also telling stories of dramatic changes. A woman in Oregon, Annette Adkins, was having seizures every week; but now hasn’t had one for eight consecutive months, according to Neurona. Heather Longo, the mother of another subject, has also said her son has gone for periods without any seizures. She’s hopeful his spirits are picking up and said that his memory, balance, and cognition, are improving.

Getting consistent results from a treatment made of living cells is not going to be easy, however. One volunteer in the study saw no benefit, at least initially, while Graves’s seizures tapered away so soon after the procedure that it’s unclear whether the new cells could have caused the change, since it can takes weeks for them to grow out synapses and connect to other cells.

“I don’t think we really understand all the biology,” says Ben-Haim.

Neurona plans a larger study to help sift through cause and effect. Nicholas says the next stage of the trial will enroll 30 volunteers, half of whom will undergo “sham” surgeries. That is, they’ll all don surgical gowns, and doctors will drill holes into their skulls. But only some will get the cells; for the rest it will be play-acting. That is to rule out a placebo effect or the possibility that, somehow, simply passing a needle into the brain has some benefit.

Justin Graves scuba diving prior to his diagnosis.
JUSTIN GRAVES

Graves tells MIT Technology Review he is sure the cells helped him. “What else could it be? I haven’t changed anything else,” he says.

Now he is ready to believe he can get parts of his life back. He hopes to swim again. And if he can drive, he plans to move home to Louisville to be near his parents. “Road trips were always something I liked,” he says. “One of the plans I had was to go across the country. To not have any rush to it and see what I want.”

Now read the rest of The Checkup 

Read more from MIT Technology Review’s archive

This summer, I checked into what 25 years of research using embryonic stem cells had delivered. The answer: lots of hype and no cures…yet.

Earlier this month, Cassandra Willyard wrote about the many scientific uses of “organoids.” These blobs of tissue (often grown from stem cells) mimic human organs in miniature and are proving useful for testing drugs and studying viral infections. 

Our 2023 list of young innovators to watch included Julia Joung, who is discovering the protein factors that tell stem cells what to develop into.

There’s a different kind of stem cell in your bone marrow—the kind that makes blood. Gene-editing these cells can cure sickle-cell disease. The process is grueling, though. In December, one patient, Jimi Olaghere, told us his story.

From around the web

The share of abortions that are being carried out with pills in the US continues to rise, reaching 63%. The trend predates the 2022 Supreme Court decision allowing states to bar doctors from providing abortions. Since then, more women may have started getting the pills outside the formal health-care system. (New York Times)

Excitement over pricey new weight-loss drugs is causing “pharmaco-amnesia,” Daniel Engber says. People are forgetting there were already some decent weight-loss pills that he says were “half as good … for one-30th the price.” (The Atlantic)

There’s a bird flu outbreak among US dairy cattle. It’s troubling to see a virus jump species, but so far, it’s not that bad for cows. “It was kind of like they had a cold,” one source told the AP. (Associated Press)

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Mar 24 2024
How scientists traced a mysterious covid case back to six toilets

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 have a mystery for you. It’s the story of how a team of researchers traced a covid variant in Wisconsin from a wastewater plant to six toilets at a single company. But it’s also a story about privacy concerns that arise when you use sewers to track rare viruses back to their source. 

That virus likely came from a single employee who happened to be shedding an enormous quantity of a very weird variant. The researchers would desperately like to find that person. But what if that person doesn’t want to be found?

A few years ago, Marc Johnson, a virologist at the University of Missouri, became obsessed with weird covid variants he was seeing in wastewater samples. The ones that caught his eye were odd in a couple of different ways: they didn’t match any of the common variants, and they didn’t circulate. They would pop up in a single location, persist for some length of time, and then often disappear—a blip. Johnson found his first blip in Missouri. “It drove me nuts,” he says. “I was like, ‘What the hell was going on here?’” 

Then he teamed up with colleagues in New York, and they found a few more.

Hoping to pin down even more lineages, Johnson put a call out on Twitter (now X) for wastewater. In January 2022, he got another hit in a wastewater sample shipped from a Wisconsin treatment plant. He and David O’Connor, a virologist at the University of Wisconsin, started working with state health officials to track the signal—from the treatment plant to a pumping station and then to the outskirts of the city, “one manhole at a time,” Johnson says. “Every time there was a branch in the road, we would check which branch [the signal] was coming from.”

They chased some questionable leads. The researchers were suspicious the virus might be coming from an animal. At one point O’Connor took people from his lab to a dog park to ask dog owners for poop samples. “There were so many red herrings,” Johnson says.

Finally, after sampling about 50 manholes, the researchers found the manhole, the last one on the branch that had the variant. They got lucky. “The only source was this company,” Johnson says. Their results came out in March in Lancet Microbe. 

Wastewater surveillance might seem like a relatively new phenomenon, born of the pandemic, but it goes back decades. A team of Canadian researchers outlines several historical examples in this story. In one example, a public health official traced a 1946 typhoid outbreak to the wife of a man who sold ice cream at the beach. Even then, the researcher expressed some hesitation. The study didn’t name the wife or the town, and he cautioned that infections probably shouldn’t be traced back to an individual “except in the presence of an outbreak.”

In a similar study published in 1959, scientists traced another typhoid epidemic to one woman, who was then banned from food service and eventually talked into having her gallbladder removed to eliminate the infection. Such publicity can have a “devastating effect on the carrier,” they remarked in their write-up of the case. “From being a quiet and respected citizen, she becomes a social pariah.”

When Johnson and O’Connor traced the virus to that last manhole, things got sticky. Until that point, the researchers had suspected these cryptic lineages were coming from animals. Johnson had even developed a theory involving organic fertilizer from a source further upstream. Now they were down to a single building housing a company with about 30 employees. They didn’t want to stigmatize anyone or invade their privacy. But someone at the company was shedding an awful lot of virus. “Is it ethical to not tell them at that point?” Johnson wondered.

O’Connor and Johnson had been working with state health officials from the very beginning. They decided the best path forward would be to approach the company, explain the situation, and ask if they could offer voluntary testing. The decision wasn’t easy. “We didn’t want to cause panic and say there’s a dangerous new variant lurking in our community,” Ryan Westergaard, the state epidemiologist for communicable diseases at the Wisconsin Department of Health Services, told Nature. But they also wanted to try to help the person who was infected. 

The company agreed to testing, and 19 of its 30 employees turned up for nasal swabs. They were all negative.

That may mean one of the people who didn’t test was carrying the infection. Or could it mean that the massive covid infection in the gut didn’t show up on a nasal swab? “This is where I would use the shrug emoji if we were doing this over email,” O’Connor says.

At the time, the researchers had the ability to test stool samples for the virus, but they didn’t have approval. Now they do, and they’re hoping stool will lead them to an individual infected with one of these strange viruses who can help answer some of their questions. Johnson has identified about 50 of these cryptic covid variants in wastewater. “The more I study these lineages, the more I am convinced that they are replicating in the GI tract,” Johnson says. “It wouldn’t surprise me at all if that’s the only place they were replicating.” 

But how far should they go to find these people? That’s still an open question. O’Connor can imagine a dizzying array of problems that might arise if they did identify an individual shedding one of these rare variants. The most plausible hypothesis is that the lineages arise in individuals who have immune disorders that make it difficult for them to eliminate the infection. That raises a whole host of other thorny questions: what if that person had a compromised immune system due to HIV in addition to the strange covid variant? What if that person didn’t know they were HIV positive, or didn’t want to divulge their HIV status? What if the researchers told them about the infection, but the person couldn’t access treatment? “If you imagine what the worst-case scenarios are, they’re pretty bad,” O’Connor says.

On the other hand, O’Connor says, they think there are a lot of these people around the country and the world. “Isn’t there also an ethical obligation to try to learn what we can so that we can try to help people who are harboring these viruses?” he asks.

Now read the rest of The Checkup

More from MIT Technology Review

Longevity specialists aim to help people live longer and healthier lives. But they have yet to establish themselves as a credible medical field. Expensive longevity clinics that cater to the wealthy worried well aren’t helping. Jessica Hamzelou takes us inside the quest to legitimize longevity medicine.

Drug developers bet big on AI to help speed drug development. But when will we see our first generative drug? Antonio Regalado has the story. 

Read more from MIT Technology Review’s archive

The covid pandemic brought the tension between privacy and public health into sharp relief, wrote Karen Hao in 2020. 

That same year Genevieve Bell argued that we can reimagine contact tracing in a way that protects privacy.

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

Earlier this year I wrote about using wastewater to track measles. 

From around the web

Surgeons have transplanted a kidney from a genetically engineered pig into a 62-year-old man in Boston. (New York Times)
→ Surgeons transplanted a similar kidney into a brain-dead patient in 2021. (MIT Technology Review) 
→ Researchers are also looking into how to transplant other organs. Just a few months ago, surgeons connected a genetically engineered pig liver to another brain-dead patient. (MIT Technology Review)

The FDA has approved a new gene therapy for a rare but fatal genetic disorder in children. Its $4.25 million price tag will make it the world’s most expensive medicine, but it promises to give children with the disease a shot at a normal life. (CNN)
→ Read Antonio Regalado’s take on the curse of the costliest drug. (MIT Technology Review)

People who practice intermittent fasting have an increased risk of dying of heart disease, according to new research presented at the American Heart Association meeting in Chicago. There are, of course, caveats. (Washington Post and Stat)

Some parents aren’t waiting to give their young kids the new miracle drug to treat cystic fibrosis. They’re starting the treatment in utero. (The Atlantic) 

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Mar 17 2024
Brazil is fighting dengue with bacteria-infected mosquitos

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.

As dengue cases continue to rise in Brazil, the country is facing a massive public health crisis. The viral disease, spread by mosquitoes, has sickened more than a million Brazilians in 2024 alone, overwhelming hospitals.

The dengue crisis is the result of the collision of two key factors. This year has brought an abundance of wet, warm weather, boosting populations of Aedes aegypti, the mosquitoes that spread dengue. It also happens to be a year when all four types of dengue virus are circulating. Few people have built up immunity against them all.   

Brazil is busy fighting back.  One of the country’s anti-dengue strategies aims to hamper the mosquitoes’ ability to spread disease by infecting the insects with a common bacteria—Wolbachia. The bacteria seems to boost the mosquitoes’ immune response, making it more difficult for dengue and other viruses to grow inside the insects. It also directly competes with viruses for crucial molecules they need to replicate. 

The World Mosquito Program breeds mosquitoes infected with Wolbachia in insectaries and releases them into communities. There they breed with wild mosquitoes. Wild females that mate with Wolbachia-infected males produce eggs that don’t hatch. Wolbachia-infected females produce offspring that are also infected. Over time, the bacteria spread throughout the population. Last year I visited the program’s largest insectary—a building in Medellín, Colombia, buzzing with thousands of mosquitoes in netted enclosures— with a group of journalists. “We’re essentially vaccinating mosquitoes against giving humans disease,” said Bryan Callahan, who was director of public affairs at the time.

At the World Mosquito Program’s insectary in Medellín, Colombia. These strips of paper are covered with Ades aegypti eggs. Dried eggs can survive for months at a time before being rehydrated, making it possible to ship them all over the world.

The World Mosquito Program first began releasing Wolbachia mosquitoes in Brazil in 2014. The insects now cover an area with a population of more than 3 million across five municipalities: Rio de Janeiro, Niterói, Belo Horizonte, Campo Grande, and Petrolina.

In Niterói, a community of about 500,000 that lies on the coast just across a large bay from Rio de Janeiro, the first small pilot releases began in 2015, and in 2017 the World Mosquito Program began larger deployments. By 2020, Wolbachia had infiltrated the population. Prevalence of the bacteria ranged from 80% in some parts of the city to 40% in others. Researchers compared the prevalence of viral illnesses in areas where mosquitoes had been released with a small control zone where they hadn’t released any mosquitoes. Dengue cases declined by 69%. Areas with Wolbachia mosquitoes also experienced a 56% drop in chikungunya and a 37% reduction in Zika.

How is Niterói faring during the current surge? It’s early days. But the data we have so far are encouraging. The incidence of dengue is one of the lowest in the state, with 69 confirmed cases per 100,000 people. Rio de Janeiro, a city of nearly 7 million, has had more than 42,000 cases, an incidence of 700 per 100,000.

“Niterói is the first Brazilian city we have fully protected with our Wolbachia method,” says Alex Jackson, global editorial and media relations manager for the World Mosquito Program. “The whole city is covered by Wolbachia mosquitoes, which is why the dengue cases are dropping significantly.”

The program hopes to release Wolbachia mosquitoes in six more cities this summer. But Brazil has more than 5,000 municipalities. To make a dent in the overall incidence in Brazil, the program will have to release millions more mosquitoes. And that’s the plan.

The World Mosquito Program is about to start construction on a mass rearing facility—the biggest in the world—in Curitiba. “And we believe that will allow us to essentially cover most of urban Brazil within the next 10 years,” Callahan says.

There are also other mosquito-based approaches in the works. The UK company Oxitec has been providing genetically modified “friendly” mosquito eggs to Indaiatuba, Brazil, since 2018. The insects that hatch—all males—don’t bite. And when they mate, their female offspring don’t survive, reducing populations. 

Another company, Forrest Brasil Tecnologia, has been releasing sterile male mosquitoes in parts of Ortigueira. When these males mate with wild females, they produce eggs that don’t hatch.  From November 2020 to July 2022, the company recorded a 98.7% decline in the Ades aegypti  population in Ortigueira. 

Brazil is also working on efforts to provide its citizens with greater immunity, vaccinating the most vulnerable with a new shot from Japan and working on its own home-grown dengue vaccine. 

None of these solutions are a quick fix. But they all provide some hope that the world can find ways to fight back even as climate change drives dengue and other infections to new peaks and into new territories. ““Cases of dengue fever are rising at an alarming rate,” Gabriela Paz-Bailey, who specializes in dengue at the US Centers for Disease Control and Prevention, told the Washington Post. “It’s becoming a public health crisis and coming to places that have never had it before.”

Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

We’ve written about the World Mosquito Program before. Here’s a 2016 story from Antonio Regalado that looked at early excitement and Bill Gates’ backing of the project. 

That same year we reported on Oxitec’s early work in Brazil using genetically modified mosquitoes. Flavio Devienne Ferreira has the story. 

And this story from Emily Mullin looks at Google’s sister company, Verily. It built a robot to create Wolbachia-infected mosquitoes and began releasing them in California in 2017. (The project is now called Debug). 

From around the web

The FDA-approved ALS drug Relyvrio has failed to benefit patients in a large clinical trial. It was approved early amidst questions about its efficacy, and now the medicine’s manufacturer has to decide whether to pull it off the  market. (NYT)

Wegovy: it’s not just for weight loss anymore. The FDA has approved a label expansion that will allow Novo Nordisk to market the drug for its heart benefits, which might prompt more insurers to cover it. (CNN)

Covid killed off one strain of the flu and experts suggest dropping it from the next flu vaccine. (Live Science) 

Scientists have published the first study linking microplastic pollution to human disease. The research shows that people with plastic in their artery tissues were twice as likely to have a heart attack, stroke, or die than people without plastic. (CNN)

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Mar 10 2024
The many uses of mini-organs

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 wrote about a team of researchers who managed to grow lung, kidney, and intestinal organoids from fetal cells floating around in the amniotic fluid. Because these tiny 3D cell clusters come from the fetus and mimic some of the features of a real, full-size organ, they can provide a sneak peek at how the fetus is developing. That’s something nearly impossible to do with existing tools.

An ultrasound, for example, might reveal that a fetus’s kidneys are smaller than they should be, but absent a glaring genetic defect, doctors can’t say why they’re small or figure out a fix. But if they can take a small sample of amniotic fluid and grow a kidney organoid, the problem might become evident, and so might a potential solution.  

Exciting, right? But organoids can do so much more!

Let’s do a roundup of some of the weird, wild, wonderful, and downright unsettling uses that researchers have come up with for organoids.

Organoids could help speed drug development. By some estimates, 90% of drug candidates fail during human trials. That’s because the preclinical testing happens largely in cells and rodents. Neither is a perfect model. Cells lack complexity. And mice, as we all know, are not humans.

Organoids aren’t humans either, but they come from humans. And they have the advantage of having more complexity than a layer of cells in a dish. That makes them a good model for screening drug candidates. When I wrote about organoids in 2015, one cancer researcher told me that studying cells to understand how an organ functions is like studying a pile of bricks to understand the function of a house. Why not just study the house?

Big Pharma appears to agree. In 2022, Roche hired organoid pioneer Hans Clevers to head its Pharma Research and Early Development division. “My belief is that human organoids will eventually complement everything we are currently doing. I’m convinced, now that I’ve seen how the whole drug development process runs, that one can implement human organoids at every step of the way,” Clevers told Nature.

Organoids are trickier to grow than cell lines, but some companies are working to make the process automated. The Philadelphia-based biotech Vivodyne has developed a robotic system that combines organoids with organ-on-a-chip technology. The system grows 20 kinds of human tissue, each containing 200,000 to 500,000 cells, and then doses them with drugs. These “lab-grown human test subjects” provide “huge amounts of complex human data—larger than you could get from any clinical trial,” said Andrei Georgescu, CEO and cofounder of Vivodyne, in a press release.

According to Viodyne’s website, the proprietary machines can test 10,000 independent human tissues at a time, “yielding vivarium-scale output.” Vivarium-scale output. I had to roll this phrase around my brain quite a few times before I understood what they meant: the robot provides the same amount of data as a building full of lab mice.

Organoids could help doctors make medical decisions for individual patients. These mini organs can be grown from stem cells, but they can also be grown from adult cells that have been nudged into a stem-like state. That makes it possible to grow organoids from anyone for any number of uses. In cancer patients, for instance, these patient-derived organoids could be used to help figure out the best therapy.

Cystic fibrosis is another example. Many cystic fibrosis therapies are approved to treat people with specific mutations. But for people who have rarer mutations, it’s not clear which therapies will work. Enter organoids.

Doctors take rectal biopsies from people with the disease, use the cells to create personalized intestinal organoids, and then apply different drugs. If a given treatment works, the ion channels open, water rushes in, and the organoids visibly swell. The results of this test have been used to guide the off-label use of these medications. In one recent case, the test allowed a woman with cystic fibrosis to access one of these drugs through a compassionate use program. 

Organoids are also poised to help researchers better understand how our bodies interact with the microbes that surround (and sometimes infect) us. During the Zika health emergency in 2015, researchers used brain organoids to figure out how the virus causes microcephaly and brain malformations. Researchers have also managed to use organoids to grow norovirus, the pathogen responsible for most stomach flus. Human norovirus doesn’t infect mice, and it has proved especially tricky to culture in cells. That’s probably part of the reason we have no therapies for the illness.  

I’ve saved the weirdest and arguably creepiest applications for last. Some researchers are working to leverage the brain’s unparalleled ability to learn by developing brain organoid biocomputers. The current iterations of these biocomputers aren’t doing any high-level thinking. One clump of brain cells in a dish learned to play the video game Pong. Another hybrid biocomputer maybe managed to decode some audio signals from people pronouncing Japanese vowels. The field is still in extremely early stages, and researchers are wary of overhyping the technology. But given where the field wants to go—full-fledged organoid intelligence—it’s not too early to talk about ethical concerns. Could a biocomputer become conscious? Organoids arise from cells taken from an individual. What rights would that person have? Would the biocomputer have rights of its own? And what about rodents that have had brain organoids implanted in them? (Yes, that’s happening too). 

Last year, researchers reported that human organoids implanted in rat brains expanded into millions of neurons and managed to wire themselves into the animal’s brain. When they blew a puff of air over the rat’s whiskers, they could record an electrical signal zipping through the human neurons.

In a 2017 Stat story on efforts to implant human brain organoids into rodents, the late Sharon Begley talked to legal scholar and bioethicist Hank Greely of Stanford University. During their conversation, he invoked the literary classic Frankenstein as a cautionary and relevant tale: “it could be that what you’ve built is entitled to some kind of respect,” he told her.

Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

In 2023, scientists reported that brain organoids  hitched to an electronic chip could perform  some very basic speech recognition tasks. Abdullahi Tsanni has the story.

Saima Sidik tells us how organoids created from the uterine lining might reveal the mysteries of menstruation. Here’s her report. 

When will we be able to transplant mini lungs, livers, or thyroids into people? Ten years …  maybe, said my colleague Jess Hamzelou in this past issue of The Checkup. 

From around the web

An Alabama bill passed on Wednesday creates a “legal moat” around embryos. Under the new law, providers and recipients of IVF could not be prosecuted or sued for damaging or destroying embryos. But the law doesn’t answer the central question raised by Alabama courts last week: Are embryos people? (NYT)

More legal news. The Senate homeland security committee passed a bill this week that would block certain Chinese biotechs from conducting business in the US. The aim is to keep them from accessing Americans personal health data and genetic information. But some critics have raised supply chain concerns. (Reuters)

Some scientists have expressed concern that too many covid shots could fatigue the immune system and make vaccination less effective. But a man who got a whopping 217 covid vaccines showed no signs of a flagging immune response. (Washington Post)

Buckle up. Norovirus is coming for you. (USA Today).Small studies showing that ibogaine, a psychedelic derived from tree bark, can treat opioid addiction have renewed interest in this illegal drug. But some researchers question whether it could ever be a feasible therapy (NYT)

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Mar 2 2024
How some bacteria are cleaning up our messy water supply

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.

The diabetes medication metformin has been touted as a miracle drug. Not only does it keep diabetes in check, but it can reduce inflammation, curb cancer, stave off the worst effects of covid, and perhaps even slow the aging process. No wonder it’s so popular. In the US, the number of metformin prescriptions has more than doubled in less than two decades, from 40 million in 2004 to 91 million in 2021.

Worldwide, we consume more than 100 million kilograms of metformin a year.  That’s staggering.

All that metformin enters the body. But it also exits largely unchanged and ends up in our wastewater. The quantities found there are tiny—tens of micrograms per liter—and not likely to harm humans. But even small amounts can affect aquatic organisms that are literally swimming in it. 

Lawrence Wackett, a biochemist at the University of Minnesota, got interested in this issue about a decade ago. Researchers had observed that at some wastewater treatment plants, the amount of metformin entering was much larger than the amount leaving. In 2022, Wackett’s team and two other groups identified the bacteria responsible for metabolizing the drug and sequenced their genomes. But Wackett still wondered which genes were responsible.

Now he knows. This week, he and his colleagues reported that they have identified two genes encoding proteins that can break down metformin. The study was published in the Proceedings of the National Academy of Sciences. These proteins are produced by at least five species of bacteria found in wastewater sludge across three continents. But here’s what struck me: This isn’t a coincidence. These bacteria evolved the ability to metabolize metformin. They saw an opportunity to capitalize on the ubiquity of the drug in their environment, and they seized it. “This happens all the time,” Wackett says. “Microbes adapt to the chemicals that we make.”

Here’s another example. In the 1960s, farmers began using a new weed killer called atrazine. For about a decade, scientists reported that the chemical appeared to degrade slowly in soil. But about a decade later, that changed. “Everybody was reporting, ‘No, it’s going away really fast—in weeks or a month.” That’s because bacteria evolved the capacity to metabolize atrazine to extract nitrogen. “There is selective pressure,” Wackett says. “The bacteria that figured out how to get that nitrogen out have a big selective advantage.”

This kind of bacterial evolution shouldn’t come as a surprise. We’ve all heard about how the rampant use of antibiotics in people and livestock is driving an antimicrobial resistance crisis. But for some reason, it never occurred to me that bacteria might be evolving in a way that could help us rather than harm us.

That’s good news. Because we have made a real mess of our water supply.

Let’s take a step back. This problem isn’t new. Scientists first detected pharmaceuticals in water more than 40 years ago. But concern has increased dramatically in the past 20 years. In 2008, the Associated Press reported that drinking water in the US was tainted with a wide variety of medications—everything from antibiotics to antidepressants to sex hormones.

It’s not just medicines. A dizzying number of personal care products also end up in the sewers—coconut shampoos and hydrating body washes and expensive face serums and … well, the list goes on and on. Wastewater treatment facilities were never designed to deal with these so-called micropollutants. “For the first 100 years or so of wastewater treatment, you know, the big thing was to prevent infectious diseases,” Wackett says.

Today, many wastewater treatment plants mix wastewater and air in a tank to form an activated sludge—a process that helps bacteria break down pollutants. This system was originally designed to remove nitrogen, phosphates, and organic matter—not pharmaceuticals. When bacteria in the sludge do metabolize drugs like metformin, it’s a happy accident, not the result of intentional design.

Certain technologies that rely on bacteria can do a better job of getting rid of these tiny pollutants. For example, membrane biological reactors combine activated sludge with microfiltration, while biofilm reactors rely on bacteria grown on the surface of membranes. There are even anaerobic “sludge blankets” (worst name ever), in which microbes convert contaminants to biogas in an oxygen-poor environment. But these technologies are expensive, and treatment facilities aren’t required to ensure that treated water is free of these contaminants. At least not in the US.

The European Commission is on its way to adopting new rules stipulating that by 2045, larger wastewater treatment facilities will have to remove a whole host of micropollutants. And in this case, the polluters—pharmaceutical and cosmetics companies—will pay 80% of the cost. The pharmaceutical industry is not a fan of this idea. Trade groups say the new rules will likely result in drug shortages.  

In the US, the federal government is still trying to figure out how to deal with these pollutants. It’s tricky, because it’s not entirely clear what impact small quantities of pharmaceuticals in water will have on the environment and human health. And the risk varies depending on the medication in question. Some pose a clear threat. Oral contraceptives, for example, have caused fertility issues and sex switching in fish. 

Could bacteria save us from estrogen too? Maybe. More than 100 estrogen-degrading microbes have been identified. We just need to find a way to harness them.

Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

In a 2023 issue of The Checkup, my colleague Jessica Hamzelou introduced us to the scientists who study the exposome—all the chemicals we eat, drink, inhale, and digest. Here’s the story.

Hamzelou also wrote about another pervasive pollutant: microplastics. They’re everywhere, and we still don’t really understand what they’re doing to us.  

Microbes aren’t just for cleaning up wastewater. They can also help break down food. And some companies hope to build anaerobic digesters to help them do just that, reported Casey Crownhart last year.

Saima Sidik dove into the fascinating history of how MIT’s innovations in wastewater treatment helped stop the spread of infectious diseases. 

From around the web

Long read: Jane Burns has devoted her life to solving the mystery of Kawasaki disease, a lethal childhood illness that comes on without warning. Now Burns and her oddball team of collaborators have the tools they need to pinpoint the cause.  (NYT)

Older adults should get another covid booster this spring, according to new CDC recommendations. (Washington Post)

Public health officials are “flummoxed” about the Florida surgeon general’s lackluster response to a measles outbreak in the state. (NPR)

After decades of little innovation, biotech finally has a bevy of new drug candidates to treat psychiatric illnesses. “This is a renaissance in neuroscience.” (Stat)

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Feb 24 2024
The weird way Alabama’s embryo ruling takes on artificial wombs

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.

A ruling by the Alabama Supreme Court last week that frozen embryos stored in labs count as children is sending “shock waves” through the fertility industry and stoking fears that in vitro fertilization is getting swept up into the abortion debate.

The New York Times reports that one clinic, at the University of Alabama, has stopped fertilizing eggs in its laboratory, fearing potential criminal prosecution.

Fertility centers create millions of embryos a year. Some are frozen and others used in research, but most are intended to be transplanted into patients’ wombs so they can get pregnant. 

The Alabama legal ruling is clearly animated by religion—there are lots of Bible quotes and references to “murder” when discussing abortion. But what hasn’t gotten as much notice is the court’s specific argument that an embryo is a child “regardless of its location.” This could have implications for future technologies in development, such as artificial wombs or synthetic embryos made from stem cells. 

The case arose from an incident at an Alabama IVF clinic, the Center for Reproductive Medicine, in which a patient wandered into a storage area and removed a container of embryos from liquid nitrogen. 

That’s when “the subzero temperatures at which the embryos had been stored freeze-burned the patient’s hand, causing the patient to drop the embryos on the floor,” the decision recounts. The embryos, consisting of just a few cells, thawed out and died.

Angered by the mishap, some families then tried to collect financial damages. They sued under Alabama’s Wrongful Death of a Minor statute, which was first written in 1872, long before test-tube babies.

The question the court felt it had to decide: Do frozen embryos count as minor children or not? 

The defendants argued, in part, that an IVF embryo can’t be a child or a person because it’s not yet in a biological womb. No womb, no baby, no birth, and no child. And this is where things start to get interesting and spiral into science fiction territory. 

Justice Jay Mitchell, writing for the majority, pounced on what he called the “latent implication” of the defense’s argument. What about a baby growing to term an artificial womb? Would it also not count as a person, he asked, just because it’s not “in utero”?

According to their ruling, the wrongful-death act “applies to all unborn children, regardless of their location,” and “no exception” can be made for embryos regardless of their age, even if they’ve been in deep freeze for a decade. Nor does the law exclude any type of “extrauterine children” science can conceive.

It’s common for judges to wrestle with complex questions as they try to apply old laws to new technology. But what’s so unusual about this decision is that the judges ended up ruling on technology that hasn’t been fully invented.

“I think the opinion is really extraordinary,” says Susan Wolf, a professor of law and medicine at the University of Minnesota. “I can’t think of another case where a court powered its ruling by looking not only at technology not actually before the court, but number two, that doesn’t exist in human beings. They can’t make a binding decision about future technology that is not even part of the case.” 

Bad law or not, the question the Alabama justices ruled on could soon be a real one. Several companies are actually developing artificial wombs to keep very premature infants alive, and other research labs are working with fluid-filled bottles in which they’ve grown mouse embryos until they are fetuses with beating hearts. 

One startup company in Israel, Renewal Bio, says it wants to grow synthetic human embryos (the kind formed by stem cells) until they are 40 days old, or more, in order to collect their tissue for transplant medicine. 

All this technology is racing along, so the question of the moral and legal rights of incubated human fetuses might not be hypothetical for very long. 

Among the dilemmas lawyers and doctors could face: If a fetus is growing in a tank, would a decision to shut off its support systems be protected under liberal states’ abortion laws, which are typically based on the rights of a pregnant person? Would a fetus engineered solely to grow organs, lacking a brain cortex and without sentience, also still be considered a child in Alabama?

So while it’s obvious that the Alabama decision reflects the justices’ religious views rather than science, and that it could hurt people who just want to have a baby, maybe it is time to think about what the court calls the “many difficult questions” the wrongful-death case has raised about “the ethical status of extrauterine children.”

Now read the rest of The Checkup

For the first time, you can easily order GMOs to plant at home. The biotech plants on sale include a bright-purple tomato and a petunia plant that glows in the dark. (MIT Technology Review)

From MIT Technology Review’s archives

Last fall, my colleague Cassandra Willyard told us everything we need to know about artificial wombs. The experimental devices, she explained, are being developed to give premature babies more time to develop. So far, they’ve been tested on lambs, but human studies are being planned.

Another kind of artificial womb is used to keep very early embryos developing longer in the lab. A startup based in Israel called Renewal Bio says it hopes to grow “synthetic” human embryos this way longer than ever before as a way of bio-printing organs. 

After the US Supreme Court overturned abortion protections in 2022, several American states moved to ban the practice. Anticipating that people may seek abortions anyway, we explained how to end a pregnancy with pills ordered from an online pharmacy. 

Around the web

Elon Musk announced on X that the first volunteer to receive a brain implant from his company Neuralink can control a computer with it and can “move a mouse around the screen just by thinking.” Some commentators are annoyed at Musk for grabbing publicity while revealing few details about the study. (Wired) 

China is the country with the world’s largest population. It has the most obese people—about 200 million of them. But new weight-loss drugs are in short supply there. (WSJ)

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Feb 17 2024
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)

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Feb 10 2024
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)

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Feb 10 2024
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)

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Jan 28 2024
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)

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