Is fake grass a bad idea? The AstroTurf wars are far from over.

A rare warm spell in January melted enough snow to uncover Cornell University’s newest athletic field, built for field hockey. Months before, it was a meadow teeming with birds and bugs; now it’s more than an acre of synthetic turf roughly the color of the felt on a pool table, almost digital in its saturation. The day I walked up the hill from a nearby creek to take a look, the metal fence around the field was locked, but someone had left a hallway-size piece of the new simulated grass outside the perimeter. It was bristly and tough, but springy and squeaky under my booted feet. I could imagine running around on it, but it would definitely take some getting used to.

My companion on this walk seemed even less favorably disposed to the thought. Yayoi Koizumi, a local environmental advocate, has been fighting synthetic-turf projects at Cornell since 2023. A petite woman dressed that day in a faded plum coat over a teal vest, with a scarf the colors of salmon, slate, and sunflowers, Koizumi compulsively picked up plastic trash as we walked: a red Solo cup, a polyethylene Dunkin’ container, a five-foot vinyl panel. She couldn’t bear to leave this stuff behind to fragment into microplastic bits—as she believes the new field will. “They’ve covered the living ground in plastic,” she said. “It’s really maddening.” 

The new pitch is one part of a $70 million plan to build more recreational space at the university. As of this spring, Cornell plans to install something like a quarter million square feet of synthetic grass—what people have colloquially called “astroturf” since the middle of the last century. University PR says it will be an important part of a “health-promoting campus” that is “supportive of holistic individual, social, and ecological well-being.” Koizumi runs an anti-plastic environmental group called Zero Waste Ithaca, which says that’s mostly nonsense.

This fight is more than just the usual town-versus-gown tension. Synthetic turf used to be the stuff of professional sports arenas and maybe a suburban yard or two; today communities across the United States are debating whether to lay it down on playgrounds, parks, and dog runs. Proponents say it’s cheaper and hardier than grass, requiring less water, fertilizer, and maintenance—and that it offers a uniform surface for more hours and more days of the year than grass fields, a competitive advantage for athletes and schools hoping for a more robust athletic program.

But while new generations of synthetic turf look and feel better than that mid-century stuff, it’s still just plastic. Some evidence suggests it sheds bits that endanger users and the environment, and that it contains PFAS “forever chemicals”—per- and polyfluoroalkyl substances, which are linked to a host of health issues. The padding within the plastic grass is usually made from shredded tires, which might also pose health risks. And plastic fields need to be replaced about once a decade, creating lots of waste.

Yet people are buying a lot of the stuff. In 2001, Americans installed just over 7 million square meters of synthetic turf, just shy of 11,000 metric tons. By 2024, that number was 79 million square meters—enough to carpet all of Manhattan and then some, almost 120,000 metric tons. Synthetic turf covers 20,000 athletic fields and tens of thousands of parks, playgrounds, and backyards. And the US is just 20% of the global market. 

Where real estate is limited and demand for athletic facilities is high, artificial turf is tempting. “It all comes down to land and demand.”

Frank Rossi, professor of turf science, Cornell

Those increases worry folks who study microplastics and environmental pollution. Any actual risk is hard to parse; the plastic-making industry insists that synthetic fields are safe if properly installed, but lots of researchers think that isn’t so. “They’re very expensive, they contain toxic chemicals, and they put kids at unnecessary risk,” says Philip Landrigan, a Boston College epidemiologist who has studied environmental toxins like lead and microplastics.

But at Cornell, where real estate is limited and demand for athletic facilities is high, synthetic turf was a tempting option. As Frank Rossi, a professor of turf science at Cornell, told me: “It all comes down to land and demand.”


In 1965, Houston’s new, domed base­ball stadium was an icon of space-age design. But the Astrodome had a problem: the sun. Deep in the heart of Texas, it shined brightly through the Astrodome’s skylights—so much so that players kept missing fly balls. So the club painted over the skylights. Denied sunlight, the grass in the outfield withered and died.

A replacement was already in the works. In the late 1950s a Ford Foundation–funded educational laboratory determined that a soft, grasslike surface material would give city kids more places to play outside and had prevailed upon the Monsanto corporation to invent one. The result was clipped blades of nylon stuck to a rubber base, which the company called ChemGrass. Down it went into Houston’s outfield, where it got a new, buzzier name: AstroTurf.

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Workers lay artificial turf at the Astrodome in Houston on July 13, 1966. Developed by Monsanto, the material was originally known as ChemGrass but was later renamed AstroTurf after the stadium.
AP PHOTO/ED KOLENOVSKY, FILE

That first generation of simulated lawn was brittle and hard, but quality has improved. Today, there are a few competing products, but they’re all made by extruding a petroleum-based polymer—that’s plastic—through tiny holes and then stitching or fusing the resulting fibers to a carpetlike bottom. That gets attached to some kind of padding, also plastic. In the 1970s the industry started layering that over infill, usually sand; by the 1990s, “third generation” synthetic turf had switched to softer fibers made of polyethylene. Beneath that, they added infill that combined sand and a soft, cheap shredded rubber made from discarded automobile tires, which pile up by the hundreds of millions every year. This “crumb rubber” provides padding and fills spaces between the blades and the backing.

In the early 1980s, nearly half the professional baseball and football fields in the US had synthetic turf. But many players didn’t like it. It got hotter than real grass, gave the ball different action, and seemed to be increasing the rate of injuries among athletes. Since the 1990s, most pro sports have shifted back toward grass—water and maintenance costs pale in comparison to the importance of keeping players happy or sparing them the risk of injury. 

But at the same time, more universities and high schools are buying the artificial stuff. The advantages are clear, especially in places where it rains either too much or not enough. A natural-grass field is usable for a little more than 800 hours a year at the most, spread across just eight months in the cooler, wetter northern US. An artificial-turf field can see 3,000 hours of activity per year. For sports like lacrosse, which begins in late winter, this makes artificial turf more appealing. Most lacrosse pitches are now synthetic. So are almost all field hockey pitches; players like the way the even, springy turf makes the ball bounce.

Furthermore, supporters say synthetic turf needs less maintenance than grass, saving money and resources. That’s not always true; workers still have to decompact the playing surface and hose it off to remove bird poop or cool it down. Sometimes the infill needs topping up. But real grass allows less playing time, and because grass athletic fields often need to be rotated to avoid damage, synthetic ground cover can require less space. Hence the market’s explosive growth in the 21st century.


The city and town of Ithaca—two separate political entities with overlapping jurisdiction over Cornell construction projects—held multiple public meetings about the university’s new synthetic fields: the field hockey pitch and a complex called the Meinig Fieldhouse. Koizumi’s group turned up in force, and a few folks who worked at Cornell came to oppose the idea too—submitting pages of citations and studies on the risks of synthetic grass.

At two of those meetings, dozens of Cornell athletes turned out to support the turf. Representatives of the university and the athletic department declined to speak with me for this story, citing an ongoing lawsuit from Zero Waste Ithaca. But before that, Nicki Moore, Cornell’s director of athletics, told a local newspaper that demand from campus groups and sports teams meant the fields were constantly overcrowded. “Activities get bumped later and later, and sometimes varsity teams won’t start practicing until 10 at night, you know?” Moore told the paper. “Availability of all-weather space should normalize scheduling a great deal.”

That argument wasn’t universally convincing. “It’s a bad idea, but that’s from the environmental perspective,” says Marianne Krasny, director of Cornell’s Civic Ecology Lab and one of the speakers at those hearings. “Obviously the athletic department thinks it’s a great idea.”

square patch of artificial turf

GETTY IMAGES

Members of Cornell on Fire, a climate action group with members from both the university and the town, joined in opposing the use of artificial turf, citing the fossil-fuel origins of the stuff. They described the nominal support of the project from student athletes as inauthentic, representing not grassroots support but, yes, an astroturf campaign. 

Sorting out the actual science here isn’t simple. Over time, the plastic that synthetic turf is made of sheds bits of itself into the environment. In one study, published in 2023 in the journal Environmental Pollution, researchers found that 15% of the medium-­size and microplastic particles in a river and the Mediterranean Sea outside Barcelona, Spain, came from artificial turf, mostly in the form of tiny green fibers. Back in 2020, the European Chemicals Agency estimated that infill material from artificial-­turf fields in the European Union was contributing 16,000 metric tons of microplastics to the environment each year—38% of all annual microplastic pollution. Most of that came from the crumb rubber infill, which Europe now plans to ban by 2031. 

This pollution worries the Cornell activists. Ithaca is famous for scenic gorges and waterways. The new field hockey pitch is uphill from a local creek that empties into Cayuga Lake, the longest of the Finger Lakes and the source of drinking water for over 40,000 people.

And it’s not just the plastic bits. When newer generations of synthetic turf switched to durable high-density polyethylene, the new material gunked up the extruders used in the manufacturing process. So turf makers started adding fluorinated polymers—a type of PFAS. Some of these environmentally persistent “forever chemicals” cause cancer, disrupt the endocrine system, or lead to other health problems. Research in several different labs has found PFAS in many types of plastic grass.

But the key to assessing the threat here is exposure. Heather Whitehead, an analytical chemist then at the University of Notre Dame, found PFAS in synthetic turf at levels around five parts per billion—but estimated it’d be in water running off the fields at three parts per trillion; for context, the US Environmental Protection Agency’s legal drinking-water limit on one of the most widespread and dangerous PFAS chemicals is four parts per trillion. “These chemicals will wash off in small amounts for long periods of time,” says Graham Peaslee, Whitehead’s advisor and an emeritus nuclear physicist who studies PFAS concentrations. “I think it’s reason enough not to have artificial turf.”

This gets confusing, though. There are over 16,000 different types of PFAS, few have been well studied, and different ­companies use different manufacturing techniques. Companies represented by the Synthetic Turf Council now “use zero intentionally added PFAS,” says Melanie Taylor, the group’s president. “This means that as the field rolls off the assembly line, there are zero PFAS-formulated materials present.”

Some researchers are skeptical of the industry’s assurances. They’re hard to confirm, especially because there are a lot of ways to test for PFAS. The type of synthetic turf going onto the new field hockey pitch at Cornell is called GreenFields TX; the university had a sample tested using an EPA method that looks for 40 different PFAS compounds. It came back negative for all of them. The local activists countered that the test doesn’t detect the specific types they’re most concerned about, and in 2025 they paid for three more tests on newly purchased synthetic turf. Two clearly found fluorine—the F in “PFAS”—and one identified two distinct PFAS compounds. (The company that makes GreenFields TX, TenCate, declined to comment, citing ongoing litigation.)

PFAS isn’t the only potential problem. There’s also the crumb rubber made from tires. A billion tires get thrown out every year worldwide, and if they aren’t recycled they sit in giant piles that make great habitats for rats and mosquitoes; they also occasionally catch fire. Lots of the tires that go into turf are made of styrene-­butadiene rubber, or SBR. In bulk, that’s bad. Butadiene is a carcinogen that causes leukemia, and fumes from styrene can cause nervous system damage. SBR also contains high levels of lead.

But how much of that comes out of synthetic-­turf infill? Again, that’s hotly debated. Researchers around the world have published suggestive studies finding potentially dangerous levels of heavy metals like zinc and lead in synthetic turf, with possible health risks to people using the fields. But a review of many of the relevant studies on turf and crumb rubber from Canada’s National Collaborating Centre for Environmental Health determined that most well-conducted health risk assessments over the last decade found exposures below levels of concern for cancer and certain other diseases. A 2017 report by the European Chemicals Agency—the same people who found all those microplastics in the environment—“found no reason to advise people against playing sports on synthetic turf containing recycled rubber granules as infill material.” And a multiyear study from the EPA, published in 2024, found much the same thing—although the researchers said that levels of certain synthetic chemicals were elevated inside places that used indoor artificial turf. They also stressed that the paper was not a risk assessment. 

The problem is, the kinds of cancers these chemicals can cause may take decades to show up. Long-term studies haven’t been done yet. All the evidence available so far is anecdotal—like a series for the Philadelphia Inquirer that linked the deaths of six former Phillies players from a rare type of brain cancer called glioblastoma to years spent playing on PFAS-containing artificial turf. That’d be about three times the usual rate of glioblastoma among adult men, but the report comes with a lot of cautions—small sample size, lots of other potential causes, no way to establish causation.

Synthetic turf has one negative that no one really disputes: It gets very hot in the sun—as hot as 150 °F (66 °C). This can actually burn players, so they often want to avoid using a field on very hot days.

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A field hockey player from Cornell University passes the ball during a game played on artificial turf at Bryant University in 2025. Cornell’s own turf field will be ready for the 2026 season.
GETTY IMAGES

Athletes playing on artificial turf also have a higher rate of foot and ankle injuries, and elite-level football players seem to be more predisposed to knee injuries on those surfaces. But other studies have found rates of knee and hip injury to be roughly comparable on artificial and natural turf—a point the landscape architect working on the Cornell project made in the information packet the university sent to the city. Athletic departments and city parks departments say that the material’s upsides make it worthwhile, given that there’s no conclusive proof of harm.

Back in Ithaca, Cornell hired an environmental consulting firm called Haley & Aldrich to assess the evidence. The company concluded that none of the university’s proposed installations of artificial turf would have a negative environmental impact. People from Cornell on Fire and Zero Waste Ithaca told me they didn’t trust the firm’s findings; representatives from Haley & Aldrich declined to comment.

Longtime activists say that as global consumption of fossil fuels declines, petrochemical companies are desperate to find other markets. That means plastics. “There’s a big push to shift more petrochemicals into plastic products for an end market,” says Jeff Gearhart, a consumer product researcher at the Ecology Center. “Industry people, with a vested interest in petrochemicals, are looking to expand and build out alternative markets for this stuff.”

All that and more went before the decision-­makers in Ithaca. In September 2024, the City of Ithaca Planning Board unanimously issued a judgment that the Meinig Fieldhouse would not have a significant environmental impact and thus would not need to complete a full environmental impact assessment. Six months later, the town made the same determination for the field hockey pitch.

Zero Waste Ithaca sued in New York’s supreme court, which ruled against the group. Koizumi and lawyers from Pace University’s Environmental Litigation Clinic have appealed. She says she’s still hopeful the court might agree that Ithaca authorities made a mistake by not requiring an environmental impact statement from the college. “We have the science on our side,” she says.


Ithaca is a pretty rarefied place, an Ivy League university town. But these same tensions—potential long-term environmental and public health consequences versus the financial and maintenance concerns of the now—are pitting worried citizens against their representatives and city agencies around the country. 

New York City has 286 municipal synthetic-­turf fields, with more under construction. In Inwood, the northernmost neighborhood in Manhattan, two fields were approved via Zoom meetings during the pandemic, and Massimo Strino, a local artist who makes kaleidoscopes, says he found out only when he saw signs announcing the work on one of his daily walks in Inwood Hill Park, along the Hudson River. He joined a campaign against the plan, gathering more than 4,300 signatures. “I was canvassing every weekend,” Strino says. “You can count on one hand, literally, the number of people who said they were in favor.” 

But that doesn’t include the group that pushed for one of those fields in the first place: Uptown Soccer, which offers free and low-cost lessons and games to 1,000 kids a year, mostly from underserved immigrant families. “It was turning an unused community space into a usable space,” says David Sykes, the group’s executive director. “That trumped the sort of abstract concerns about the environmental impacts. I’m not an expert in artificial turf, but the parks department assured me that there was no risk of health effects.”

Artificial turf doesn’t go away. “You’re going to be paying to get rid of it. Somebody will have to take it to a dump, where it will sit for a thousand years.”

Graham Peaslee, emeritus nuclear physicist studying PFAS concentrations, University of Notre Dame

New York City councilmember Christopher Marte disagrees. He has introduced a bill to ban new artificial turf from being installed in parks, and he hopes the proposal will be taken up by the Parks Committee this spring. Last session, the bill had 10 cosponsors—that’s a lot. Marte says he expects resistance from lobbyists, but there’s precedent. The city of Boston banned artificial turf in 2022.  

Upstate, in a Rochester suburb called Brighton, the school district included synthetic-­turf baseball and softball diamonds in a wide-ranging February 2024 capital improvement proposition. The measure passed. In a public meeting in November 2025, the school board acknowledged the intent to use synthetic grass—or, as concerned parents had it, “to rip up a quarter ­million square feet of this open space and replace it with artificial turf,” says David Masur, executive director of the environmental group PennEnvironment, whose kids attend school in Brighton. Parents and community members mobilized against the plan, further angered when contractors also cut down a beloved 200-year-old tree. School superintendent Kevin McGowan says it’s too late to change course. Masur has been working to oppose the plan nevertheless—he says school boards are making consequential decisions about turf without sharing information or getting input, even though these fields can cost millions of dollars of taxpayer money.

In short, the fights can get tense. On Martha’s Vineyard, in Massachusetts, a meeting about plans to install an artificial field at a local high school had to be ended early amid verbal abuse. A staffer for the local board of health who voiced concern about PFAS in the turf quit the board after discovering bullet casings in her tote bag, she said, which she perceived as a death threat. After an eight-year fight, the board eventually banned artificial turf altogether. 


What happens next? Well, outdoor artificial turf lasts only eight to 12 years before it needs to be taken up and replaced. The Synthetic Turf Council says it’s at least partially recyclable and cites a company called BestPLUS Plastic Lumber as a purveyor of products made from recycled turf. The company says one of its products, a liner called GreenBoard that artificial turf can be nailed into, is at least 40% recycled from fake grass. Joseph Sadlier, vice president and general manager of plastics recycling at BestPLUS, says the company recycles over 10 million pounds annually. 

Yet the material is piling up. In 2021, a Danish company called Re-Match announced plans to open a recycling plant in Pennsylvania and began amassing thousands of tons of used plastic turf in three locations. The company filed for bankruptcy in 2025.

In Ithaca, university representatives told planning boards that it would be possible to recycle the old artificial turf they ripped out to make way for the Meinig Fieldhouse. That didn’t happen. An anonymous local activist tracked the old rolls to a hauling company a half-hour’s drive south of campus and shared pictures of them sitting on the lot, where they stayed for months. It’s unclear what their ultimate fate will be.

That’s the real problem: Artificial turf just doesn’t go away. “You’re going to be paying to get rid of it,” says Peaslee, the PFAS expert. “Somebody will have to take it to a dump, where it will sit for a thousand years.” At minimum, real grass is a net carbon sink, even including installation and maintenance. Synthetic turf releases greenhouse gases. One life-­cycle analysis of a 2.2-acre synthetic field in Toronto determined that it would emit 55 metric tons of carbon dioxide over a decade. Plastic fields need less water to maintain, but it takes water to make plastic, and natural grass lets rainwater seep into the ground. Synthetic turf sends most of it away as runoff.

It’s a boggling set of issues to factor into a decision. Rossi, the Cornell turf scientist, says he can understand why a school in the northern United States might go plastic, even when it cares about its students’ health. “It was the best bad option,” he says. Concerns about microplastics and PFAS are “significant issues we have not fully addressed.” And they need to be. 

Douglas Main is a journalist and former senior editor and writer at National Geographic.

Single-Cell Atlas of Maternal–Fetal Interface Sheds Light on Pregnancy Complications

The biological connection between a pregnant woman and her developing baby—the human maternal–fetal interface—is a specialized, transient organ composed of uterine cells from the mother and fetal cells that acts as a barrier, supports fetal growth, and maintains the mother’s health. The cellular complexity of the maternal-fetal interface has limited scientists’ ability to study how healthy pregnancies develop and why complications arise. The underlying cellular, molecular, and spatial programs of the interface—which forms about a week after fertilization and lasts until birth—has remain incompletely defined.

Now, the human maternal–fetal interface has been mapped in unprecedented detail by scientists at the University of California, San Francisco (UCSF), revealing new cell types and providing insights into conditions such as preeclampsia, preterm birth, and miscarriage.

“By examining this tissue cell by cell across pregnancy, we can begin to understand both normal development and what may go wrong,” said Susan J. Fisher, PhD, professor of obstetrics, gynecology, and reproductive sciences at UCSF.

The team generated a comprehensive atlas of the human maternal–fetal interface across normal pregnancies, from early gestation to term. The researchers did this by “integrating large-scale paired single-nucleus transcriptomic and chromatin accessibility profiling with submicrometer-resolution spatial transcriptomics and CODEX multiplex protein imaging.”

Using these tools, the researchers analyzed about 200,000 individual cells and compared them with nearly one million cells in their original positions within the uterine and placental tissue. This enabled them to identify different cell types, track how they develop, and see how they are linked to pregnancy complications.

“This work gives us a much clearer picture of this critical region than ever before,” said Jingjing Li, PhD, associate professor in UCSF’s Department of Neurology and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

This work is published in Nature in the paper, “Single-Cell Spatiotemporal Dissection of the Human Maternal–Fetal Interface.”

The atlas revealed a previously unknown maternal cell type located where fetal placental cells first enter the uterus. These cells appear to regulate how deeply placental cells invade uterine tissue, a process that is essential for establishing blood flow to the fetus. The researchers found that these cells carry a cannabinoid receptor, and exposure to cannabinoid molecules caused them to further restrict placental cell invasion.

“Population studies have linked cannabis use during pregnancy to poorer outcomes,” said Cheng Wang, PhD, a postdoctoral fellow at UCSF. “This cell type may help explain the biological basis of that association.”

To understand how complications arise, the team integrated genetic data from more than 10,000 patients. They mapped genetic risk signals for conditions including preterm birth, preeclampsia, and miscarriage onto regulatory regions of DNA that control gene activity. This approach allowed the researchers to identify the specific cell types and states most strongly associated with each condition.

The team then focused on preeclampsia, a potentially life-threatening disorder marked by sudden high blood pressure. They found that the most affected cell types are involved in remodeling the mother’s uterine blood vessels, a process required to supply adequate blood to the placenta. The findings suggest that preeclampsia may result from disrupted communication between maternal and fetal cells that normally coordinate this process.

Having established a detailed map of healthy pregnancies, the researchers plan to study complicated pregnancies to identify potential targets for treatment.

The post Single-Cell Atlas of Maternal–Fetal Interface Sheds Light on Pregnancy Complications appeared first on GEN – Genetic Engineering and Biotechnology News.

The Download: water threats in Iran and AI’s impact on what entrepreneurs make

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

Desalination plants in the Middle East are increasingly vulnerable 

As the conflict in Iran has escalated, a crucial resource is under fire: the desalinization technology that supplies water in the region. 
 
President Donald Trump has threatened to destroy “possibly all desalinization plants” in Iran if the Strait of Hormuz is not reopened. The impact on farming, industry, and—crucially—drinking in the Middle East could be severe. Find out why

—Casey Crownhart 

This story is part of MIT Technology Review Explains, our series untangling the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here. 

AI is changing how small online sellers decide what to make 

For small entrepreneurs, deciding what to sell and where to make it has traditionally been a slow, labor-intensive process. Now that work is increasingly being done by AI.   

Tools like Alibaba’s Accio compress weeks of product research and supplier hunting into a single chat. Business owners and e-commerce experts say they’re making sourcing more accessible—and slashing the time from product idea to launch.  

Read the full story on how AI is leveling the path to global manufacturing

—Caiwei Chen 

The gig workers who are training humanoid robots at home 

When Zeus, a medical student in Nigeria, returns to his apartment from a long day at the hospital, he straps his iPhone to his forehead and records himself doing chores.  
 
Zeus is a data recorder for Micro1, which sells the data he collects to robotics firms. As these companies race to build humanoids, videos from workers like Zeus have become the hottest new way to train them.   
 
Micro1 has hired thousands of them in more than 50 countries, including India, Nigeria, and Argentina. The jobs pay well locally, but raise thorny questions around privacy and informed consent. The work can be challenging—and weird. Read the full story.  

—Michelle Kim 

This is our latest story to be turned into an MIT Technology Review Narrated podcast, which we’re publishing each week on Spotify and Apple Podcasts. Just navigate to MIT Technology Review Narrated on either platform, and follow us to get all our new content as it’s released. 

The must-reads 

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology. 

1 Anthropic’s new model found security problems in every OS and browser 
Claude Mythos has been heralded as a cybersecurity “reckoning.” (The Verge)  
+ Anthrophic is limiting the rollout over hacking fears. (CNBC
+ It’s also launching a project that lets Mythos flag vulnerabilities. (Gizmodo
+ Apple, Google, and Microsoft have joined the initiative. (ZDNET

2 Iranian hackers are targeting American critical infrastructure 
Their focus is on energy and water infrastructure. (Wired
+ They’re targeting industrial control devices. (TechCrunch)  

3 Google’s AI Overviews deliver millions of incorrect answers per hour 
Despite a 90% accuracy rate. (NYT $) 
+ AI means the end of internet search as we’ve known it. (MIT Technology Review

4 Elon Musk is trying to oust OpenAI CEO Sam Altman in a lawsuit 
As remedies for Altman allegedly defrauding him. (CNBC
+ Musk wants any damages given to OpenAI’s nonprofit arm. (WSJ $) 

5 ICE has admitted it’s using powerful spyware 
The tools that can intercept encrypted messages. (NPR
+ Immigration agencies are also weaponizing AI videos. (MIT Technology Review

6 Greece has joined the countries banning kids from social media 
Under-15s will be blocked from 2027. (Reuters
+ Australia introduced the world’s first social media ban for children. (Guardian
+ Indonesia recently rolled out the first one in Southeast Asia. (DW)  
+ Experts say they’re a lazy fix. (CNBC

7 Intel will help Elon Musk build his Terafab in Texas 
They aim to manufacture chips for AI projects. (Engadget
+ Musk says it will be the largest-ever semiconductor factory. (Engadget
+ Future AI chips could be built on glass. (MIT Technology Review)  

8 TikTok is building a second billion-euro data center in Finland 
It’s moving data storage for European users. (Reuters
+ Finland has become a magnet for data centers. (Bloomberg $) 
+ But nobody wants one in their backyard. (MIT Technology Review

9 Plans for Canada’s first “virtual gated community” have sparked a row 
The AI-powered surveillance system has divided neighbors. (Guardian
+ Is the Pentagon allowed to surveil Americans with AI? (MIT Technology Review

10 The high-tech engineering of the “space toilet” has been revealed 
Artemis II is the first mission to carry one around the world. (Vox

Quote of the day 

“This case has always been about Elon generating more power and more money for what he wants. His lawsuit remains nothing more than a harassment campaign that’s driven by ego, jealousy and a desire to slow down a competitor.” 

—OpenAI criticizes Musk’s legal action in an X post

One More Thing 

USWDS

Inside the US government’s brilliantly boring websites 

You may not notice it, but your experience on every US government website is carefully crafted. 

Each site aligns an official web design and a custom typeface. They aim to make government websites not only good-looking but accessible and functional for all. 

MIT Technology Review dug into the system’s history and features. Find out what we discovered

—Jon Keegan 

We can still have nice things 

A place for comfort, fun and distraction to brighten up your day. (Got any ideas? Drop me a line.) 

+ Rejoice in the splendor of the “Earthset” image captured by Artemis II. 
+ Meet the fearless cat chasing off bears. 
+ This document vividly explains what makes the octopus so unique. 
+ Revealed: the rhythmic secret that makes emo music so angsty

Organ-on-Chip Integrated Into Preclinical Glioblastoma Research

Dynamic42 and EPO (Experimental Pharmacology and Oncology), both based in Germany, report that they are addressing the limited availability of preclinical models in brain cancer research by forming a strategic collaboration that focuses on bringing organ-on-chip technologies “closer to the core of preclinical drug development.”

The partnership combines Dynamic42’s organ-on-chip platforms with EPO’s expertise in translational oncology and access to well-characterized tumor models and patient-derived material. Together, the teams are developing experimental setups designed to reflect human tumor biology more closely and generate data that translates more reliably into clinical outcomes.

The first joint projects target glioblastoma and the blood–brain barrier (BBB). Using Dynamic42’s human-based BBB-on-chip model, the partners will explore how differences between human and non-human BBB-biology can influence therapeutic responses, which is a major factor for the limited activity of brain cancer drugs.

“Too often, critical decisions in drug development rely on data that do not fully reflect human biology,” said Thomas Sommermann, PhD, head of cancer research at Dynamic42. “We want to change that. By bringing human-based models earlier into the process, we can sharpen decision-making and reduce late-stage failure risks.”

“For us, this collaboration is about strengthening the translational link,” added Jens Hoffmann, CEO at EPO. “Integrating advanced in vitro systems allows us to look at tumor biology from a different angle and to build robust experimental in vivo strategies.”

The collaboration is designed as a complementary approach that connects established preclinical in vivo expertise with emerging human-based in vitro technologies. It supports more targeted, biology-driven research strategies and the principles of the 3Rs (Replace, Reduce, Refine), contributing to the ongoing shift toward more human-relevant experimental systems.

Beyond joint research, the partnership includes model development activities, elaboration of commercialization strategies, and close scientific exchange, including collaboration between early-career researchers from both organizations.

Dynamic42 and EPO will jointly present the first results of their collaboration at the American Association for Cancer Research® Annual Meeting 2026. Both companies plan to expand the collaboration further, exploring additional indications and extending the use of organ-on-chip technologies across different areas of drug development.

The post Organ-on-Chip Integrated Into Preclinical Glioblastoma Research appeared first on GEN – Genetic Engineering and Biotechnology News.

Team approach to lowering high blood pressure worked even in ‘a tough landscape’

It’s the leading risk factor for the leading cause of death in the United States and around the world: high blood pressure, the prime mover in heart attacks and strokes.

High blood pressure is treatable, but despite having access to effective and affordable medications, more than half of Americans still have uncontrolled hypertension, with rates going up in sync with adverse social determinants of health. 

Read the rest…

STAT+: Trump administration drops court fight to cap NIH payments for research overhead costs

The Trump administration will not be asking the Supreme Court to take up its fight to slash federal support for funding that the nation’s science enterprise relies on for basic operating costs. The deadline to do so came and went this week without a petition from Trump’s Department of Justice, effectively ending the 14-month standoff over a controversial policy to drastically reduce the rate of reimbursement for “indirect costs” on federal grants. 

The legal battle between the administration and the research community started last February, when the National Institutes of Health abruptly announced it would cap payments for research overhead at 15%. Three lawsuits opposing the caps were immediately filed by state attorneys general and organizations representing private and public universities, hospitals, and academic medical centers. 

Under the previous policy, these institutions would negotiate with the NIH for individual rates — to cover expenses not directly linked to the goals of a particular project, like facility upkeep and salaries for grant management staff. Many of the nation’s most elite research institutions typically receive 50% or more of their direct research expenses to cover indirect costs.

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Neuroblastoma Tumor Growth in Mice Suppressed by Blocking Enzyme to Inhibit mTOR Signaling

Neuroblastoma is the most common tumor among children under a year of age, and while in its gentlest form neuroblastoma can regress on its own, it can also take an aggressive form, with high-risk neuroblastoma carrying a five-year survival rate of about 40%.

Researchers at The Hebrew University of Jerusalem have now discovered a mechanistic explanation for how neuroblastoma sustains itself and identified a potential approach to severing that mechanism, by inhibiting nitric oxide (NO) production to suppress mTOR signaling. The collective results from work in human neuroblastoma cells and experiments in a mouse xenograft model showed that inhibiting the enzyme neuronal nitric oxide synthase (nNOS) to inhibit NO production suppressed mTOR signaling and slowed tumor growth.

Professor Haitham Amal, PhD, head of The Laboratory of Neuromics, Cell Signaling, and Translational Medicine, is senior and co-corresponding author of the team’s published paper in Brain Medicine, titled “Targeting nNOS suppresses AKT–TSC–mTOR signaling and inhibits neuroblastoma growth.” In their paper the team concluded “Inhibition of nNOS suppresses mTOR signaling, reduces cellular malignancy, and attenuates tumor growth in vivo, identifying the nNOS-mTOR axis as a promising therapeutic target in neuroblastoma.”

Neuroblastoma accounts for roughly 28% of all cancers diagnosed in infants across Europe and the United States. “Neuroblastoma (NB) refers to a spectrum of neuroblastic tumors that originate from the neural crest cells during fetal development,” the authors wrote. “Neuroblastoma is predominantly a pediatric malignancy, with approximately 97% of cases occurring in children.”

NBs can range from spontaneous regression to maturation to an aggressive, deadly metastatic disease. And as the investigators noted, “Despite major advances in multimodal therapy, high-risk neuroblastoma remains associated with poor prognosis, frequent relapse, and therapy resistance, underscoring the need for a better understanding of the signaling pathways that regulate tumor cell survival, differentiation, and metabolic adaptation.”

Nitric oxide (NO) is an essential regulator of carcinogenesis in various tumors, including NB, the authors pointed out. “Nitric oxide (NO) is a ubiquitous free radical signaling molecule produced in multiple organs and tissues), such as those of the central and peripheral nervous systems.” But at elevated concentrations NO becomes reactive, generating nitrogen species that chemically modify proteins through a process called S-nitrosylation. That modification has been implicated in every stage of cancer progression.

The relationship between nitric oxide and tumors is not simple. Very high concentrations can damage DNA and trigger apoptosis. Lower, sustained levels appear to do the opposite, promoting survival and metastasis. Amal and colleagues had previously demonstrated that nitric oxide drives glioblastoma progression. The question that remained was whether the same enzyme, neuronal nitric oxide synthase, was performing a similar service for neuroblastoma, and if so, through which downstream pathway. The answer turned out to be mTOR.

The team attacked nNOS from two directions. They treated human SH-SY5Y neuroblastoma cells with BA-101, a selective pharmacological inhibitor, at 100 μM for 24 hours. Separately, they silenced the nNOS gene with small interfering RNA. The reasoning was that if a drug and a genetic tool produce the same result, you are looking at biology, not pharmacological noise.

The experiments produced the same result. BA-101 reduced NADPH-diaphorase activity, the standard readout of NOS function, by 35-40%. Genetic silencing cut it by 45-50%. Nitrite levels, a stable proxy for nitric oxide production, fell 65-70% with BA-101 and 55-60% with siRNA. Colony formation, the most direct measure of proliferative capacity, dropped significantly after both BA-101 treatment (p < 0.001) and nNOS silencing (p < 0.01). The cells were losing their ability to multiply.

What followed downstream was systematic. Protein tyrosine nitration, measured by 3-nitrotyrosine immunoreactivity, fell sharply after BA-101 treatment (p < 0.01) and nNOS silencing (p < 0.001). The chemical signature of nitrosative stress was fading.

The results then confirmed that AKT phosphorylation decreased (p < 0.01 with BA-101; p < 0.05 with siRNA), while total AKT remained unchanged. Phosphorylation of mTOR itself declined under both conditions (p < 0.01 each). The downstream mTORC1 substrate ribosomal protein S6 followed (p < 0.05 with BA-101; p < 0.01 with siRNA).

And here, the most telling detail, that TSC2, a master negative regulator of mTOR signaling, rose significantly under both treatments (p < 0.05). Removing the nitric oxide signal had allowed the cell’s own braking system to re-engage. In summary, the authors noted, “Pharmacological inhibition of nNOS with BA-101 (100 μM, 24 h) or genetic silencing of nNOS with siRNA caused upregulation of the key negative regulator TSC2 and decreased phosphorylation of AKT, mTOR, and RPS6, indicating suppression of mTOR pathway activity.”

Synaptophysin, a neuroendocrine tumor marker used to gauge the malignant identity of neuroblastoma cells, decreased significantly with BA-101 (p < 0.01) and nNOS knockdown (p < 0.05). The tumor cells were not merely growing more slowly. They were becoming, at a molecular level, less recognizably cancerous. In summary, the investigators noted, “Our results show that inhibition of NO production in the human NB cell line (SH-SY5Y cells), either by pharmacological intervention using the selective nNOS inhibitor BA-101 (41) or by genetic ablation using the specific siRNA, successfully suppressed NB malignancy.”

Schematic model illustrating the NO-mTOR signaling axis in neuroblastoma. Under basal/pathological conditions (left panel), and nNOS inhibition (right panel). [Haitham Amal]
Schematic model illustrating the NO-mTOR signaling axis in neuroblastoma. Under basal/pathological conditions (left panel), and nNOS inhibition (right panel). [Haitham Amal]

But if blocking nitric oxide suppresses mTOR signaling, then flooding the cell with nitric oxide should amplify it. The researchers tested this by exposing SH-SY5Y cells to SNAP, a nitric oxide donor, at 200 μM for 24 hours. This converse experiment produced the converse result. 3-nitrotyrosine rose (p < 0.05), and TSC2 fell (p < 0.01). Phosphorylation of AKT, mTOR, and RPS6 all increased (p < 0.05 for each).

The team then tested their findings in a xenograft mouse model of neuroblastoma, treated with BA-101. “Importantly, to extend these findings to an in vivo context, we further assessed the impact of pharmacological nNOS inhibition on tumor growth in a xenograft NB model,” they stated. The investigators found that while tumors in control animals grew to approximately 1.5 cm in their largest dimension, the treated tumors did not. Final tumor volume and weight were dramatically reduced in the BA-101 group. ‘Quantitative analysis revealed a dramatic decrease in the final tumor volume and weight in the BA-101-treated group (p < 0.001) compared with controls,” they noted.

Body weight did not differ significantly between groups, suggesting that the compound was tolerated without gross systemic toxicity. In summary, the authors wrote, “Our finding demonstrate that the pro-tumorigenic effects of nNOS in SH-SY5Y involve activation of themTOR signaling pathway.” Importantly, both genetic inhibition of nNOS using siRNA and pharmacological inhibition with BA-101 effectively suppressed mTOR pathway activation and reduced malignant properties of NB cells, highlighting the therapeutic relevance of targeting nNOS signaling.  “These findings indicate that pharmacological inhibition of nNOS effectively suppresses xenograft tumor progression, highlighting the critical role of nNOS-derived NO in promoting neuroblastoma growth in vivo.”

“The magnitude of the in vivo suppression caught our attention,” said Amal, the study’s corresponding author, who holds appointments at the Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, and the Rosamund Stone Zander and Hansjoerg Wyss Translational Neuroscience Center at Boston Children’s Hospital, Harvard Medical School. “We had demonstrated the role of nitric oxide in glioblastoma previously, but the consistency of the neuroblastoma results across every assay, from protein phosphorylation to colony formation to xenograft growth, points to nNOS as something more than a contributor. It appears to be a central driver of the signaling that sustains this tumor.”

Added first author Shashank Kumar Ojha, PhD, first author of the study and a researcher at the Institute for Drug Research, The Hebrew University of Jerusalem, added, “What convinced me was the concordance between the pharmacological and genetic approaches. When BA-101 and siRNA independently produce the same pattern of effects across NADPH-diaphorase activity, nitrosative stress markers, mTOR pathway phosphorylation, and clonogenic growth, you can be confident the biology is real. That reproducibility is what gives you a therapeutic hypothesis worth testing further.”

The authors acknowledged limitations to their study. The in vitro work relied on a single cell line, SH-SY5Y, which cannot capture the full genetic heterogeneity of neuroblastoma or the complexity of the tumor microenvironment. The chemical identity of BA-101 is currently undisclosed pending patent issuance, which means independent replication by other laboratories must wait. Whether nitrosative stress directly underlies its functional impairment, or whether an intermediary mechanism is involved, remains an open question that the authors explicitly flag for future investigation. “Future studies using patient-derived cells, organoids, or genetically engineered mouse models will be important to further validate and extend these observations,” they stated. Nevertheless, the authors suggest, the limitations do not diminish the central discovery of a druggable nNOS–mTOR axis.

mTOR inhibitors such as rapalogs and catalytic mTOR inhibitors have shown limited efficacy as monotherapies in neuroblastoma, undermined by feedback activation and resistance mechanisms. The present study suggests the potential for a different attack strategy. Rather than targeting mTOR at the lock, intervene upstream at the hand that turns the key. By reducing nitric oxide-dependent mTOR activation, nNOS inhibition may sidestep the compensatory pathways that have frustrated direct mTOR blockade. “Collectively, these results identify the nNOS-mTOR axis as a key driver of neuroblastoma progression and suggest that nNOS inhibition represents a promising strategy for NB treatment,” they concluded.

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Predicting Momentary Suicidal Ideation From Smartphone Screenshots Using Vision-Language Models: Prospective Machine Learning Study

Background: Passive smartphone sensing shows promise for suicide prevention, but behavioral metadata (GPS, screen time, and accelerometry) often lacks the contextual information needed to detect acute psychological distress. Analyzing what people actually see, read, and type on their phones—rather than just usage patterns—may provide more proximal signals of risk. Objective: This study aimed to test whether vision-language models (VLMs) applied to passively captured smartphone screenshots can predict momentary suicidal ideation (SI). Methods: Seventy-nine adults with past month suicidal thoughts or behaviors completed ecological momentary assessments (EMA) over 28 days while screenshots were captured every 5 seconds during active phone use. We fine-tuned open-source VLMs (Qwen2.5-VL [Alibaba Cloud], LFM2-VL [Liquid AI]), and text-only models (Qwen3 [Alibaba Cloud]) to predict SI from screenshots captured in the 2 hours preceding each EMA. We evaluated performance with temporal and subject holdouts. Results: The analytic sample comprised 2.5 million screenshots from 70 participants. Temporal holdout models achieved strong discrimination at the EMA level (AUC=0.83; AUPRC=0.77), with image-based models outperforming text-only models (AUC=0.83 vs 0.79; 95% CI 0.003-0.07). Subject holdout generalization was near chance (AUC≈0.50), though a simple lexical screening method retained modest discrimination (AUC=0.62). Smaller models performed comparably to larger models, supporting feasible on-device deployment. Conclusions: Screen content predicts short-term SI with clinically meaningful accuracy when models are personalized but does not generalize across individuals. These findings support a 2-stage clinical architecture, coarse lexical screening for new patients, with personalized VLM-based monitoring after a calibration period. On-device inference may enable privacy-preserving deployment.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/ce9a296732ecb1406f4fc62d4f58986f" />

Bladder Cancer: Urine Test Improves Relapse Predictions

Stanford researchers have developed a urine test that can accurately predict which patients with bladder cancer will respond to standard surgery and immunotherapy treatments. In a study published in Cell, they report that this DNA test takes into account background mutations caused by aging that existing tests may otherwise mistake for cancer. 

“Our test can detect minimal residual disease non-invasively after bladder cancer treatment, while accounting for mutations present in normal urothelium that have complicated prior studies,” said Joseph C. Liao, MD, professor of urology and senior author of the study. “For the first time, we were able to distinguish patients likely cured by [immunotherapy] from those cured by surgery.”

Even when detected in early stages, bladder cancer has a high relapse rate. Patients with non-muscle invasive bladder cancer (NMIBC), whose tumors are still confined to the inner layers of the bladder, are typically treated with surgery. Those with higher risk profiles are then given a bacillus Calmette Guerin (BCG) immunotherapy, which can significantly reduce recurrence risk after surgery. 

However, while some patients respond well to surgery without immunotherapy, others may end up relapsing even after receiving BCG immunotherapy. Until now, there was no reliable way to predict which patients will respond to each of these treatments, making it difficult for physicians and patients alike to make informed clinical decisions. 

The molecular test developed by Liao and colleagues analyzes urine tumor DNA in urine samples to detect the presence of tumor DNA and predict whether a patient will respond to standard surgery or BCG treatment. Importantly, the test was designed to account for the “field effect,” a phenomenon where even healthy people can carry cancer-associated mutations in the bladder’s lining, with these mutations becoming increasingly common as the person ages. 

“By correcting for the field effect, a known confounder of mutation-based bladder cancer detection, we improved the specificity of urine tumor DNA liquid biopsies,” said William Y. Shi, MD/PhD student at Stanford School of Medicine and lead author of the study. “This allowed us to molecularly distinguish the relative contributions of surgery and BCG to disease control.”

The researchers evaluated the urine test in a cohort of 261 NMIBC patients who underwent surgery and BCG treatment. Results revealed three distinct molecular patterns of treatment response. These included surgery responders, for whom tumor DNA disappeared after surgery; BCG responders, who showed tumor DNA after surgery that was eliminated with the immunotherapy; and non-responders who saw tumor DNA levels remain stable or even increase after both treatments. 

“The ability to distinguish responders from non-responders to the two treatments also allowed us to study which molecular properties make tumors more likely to benefit from each therapy,” said Max Diehn, MD, PhD, professor of radiation oncology and senior author of the study. 

The study also revealed distinct molecular patterns driving response to surgery and response to BCG immunotherapy. On the one hand, patients who relapsed after surgery had tumors with genetic activity linked to cell growth and invasion. On the other hand, tumors who responded to BCG had a higher mutation burden and tended to have features that made them more visible to the immune system. 

Following validation in a larger patient cohort, this urine test could help spare patients who respond well to surgery from receiving an unnecessary course of immunotherapy. In particular, BCG supply has suffered from shortages for the past decade, leaving many patients waiting for longer than necessary. In the face of shortages, a predictive test could help prioritize those who are most likely to benefit from it. 

For patients who are unlikely to respond to both surgery and BCG, the urine test could also prove valuable in escalating treatment early on. In the study, the test was able to identify recurrence risk in patients for whom routine cystoscopy exams appeared normal, meaning it could be able to detect relapse earlier than the current standard. 

“These kinds of predictive biomarkers are critical,” said Eila C. Skinner, MD, professor of urology and chair of Stanford’s Department of Urology. “We have new treatments that are costly and carry risk of side effects. We would love to personalize therapy to ensure each patient receives the best treatment for their individual cancer.”

The post Bladder Cancer: Urine Test Improves Relapse Predictions appeared first on Inside Precision Medicine.

Scalable Embryonic Stem Cell Platform Enables Mitochondrial DNA Research in Mice

Salk Institute scientists have developed a biological platform for studying mitochondrial DNA in physiology, adaptation, disease mechanisms, and therapeutic development. Headed by Ronald Evans, PhD, professor and director of the Gene Expression Laboratory and holder of the March of Dimes Chair in Molecular and Developmental Biology at Salk, the team has already used the platform to generate a library of 155 mitochondrial DNA mutant cell lines and reveal correlations between mouse development and mitochondrial function. They suggest that the platform, library, and findings will accelerate therapeutic development for mitochondrial disorders, as well as help scientists treat mitochondrial dysfunction in other diseases and conditions like cancer or aging.

“Mitochondrial DNA accumulates mutations at a high rate, and more than 260 inherited disease-causing mtDNA mutations have been identified in humans,” said Evans. “Until now, a lack of models representing this diversity has limited mechanistic insight and therapeutic development. Our new platform will allow scientists to investigate mitochondrial DNA variation in health, disease, and evolution, which will enable therapeutic innovation for mitochondrial disorders.”

Evans is co-corresponding author of the team’s published paper in PNAS, titled “A scalable embryonic stem cell–based platform for efficient generation of mitochondrial DNA mutant mice,” in which they concluded that their new platform, “… opens the door to mechanistic dissection of how mtDNA variation influences metabolism, adaptation, and disease, and provides a strategically valuable foundation for accel­erating therapeutic development through genetically precise mito­chondrial disease models.”

Some of your most important life partners are the mitochondria that power all your cells. You and these little cellular powerhouses are in a 1.5-billion-year-old evolutionary relationship—but mitochondria brought some baggage. Mitochondria brought their own DNA with them when they joined with the bigger, more complex cells so long ago, and today that mitochondrial DNA influences human health. Mitochondrial DNA does the extremely important job of creating the proteins needed for energy production—but it also has an especially high rate of mutation, and those mutations can accumulate thanks to inefficient repair mechanisms. Because mitochondria are essential parts of every cell, their dysfunction can lead to body-wide dysfunction, with especially devastating impact on high-energy organs like the brain and heart. Without enough power in your cells, symptoms like migraines, muscle weakness, and loss of hearing or sight can begin to manifest.

“Mitochondria are central to energy metabolism and cellular signaling, and mutations in mitochondrial DNA (mtDNA) can disrupt these processes and contribute to human disease,” the authors wrote. “Mitochondrial DNA (mtDNA) accumulates mutations at a high rate, and more than 260 pathogenic germline mtDNA mutations have been identified in humans, producing diverse and often tissue-specific disorders.”

The chronic and broad impact of mitochondrial dysfunction makes it especially important to study. However, trying to pinpoint the outcome of specific mitochondrial DNA mutations has for many years been a slow, arduous process for many years. “… progress in defining how mtDNA variation influences adaptation, pathophysiology, and disease susceptibility has been limited by the lack of suitable animal models,” the team continued. “Researchers would create mouse models one-by-one with different mitochondrial DNA mutations, with just one model sometimes taking years,” said Salk staff scientist Weiwei Fan, PhD. This was a problem that Fan had noted early in his scientific career and set his mind to as a PhD student.

The new Salk model is a scalable, embryonic stem-cell (ES)-based platform creating mice with mutations to their mitochondrial DNA. “This new work is all building off an original platform I generated during my PhD,” says Fan, first and co-corresponding author of the study. “That platform was inefficient—it took a long time to generate just one mitochondrial DNA mutant. With some technological improvements and modifications, this new platform is much more efficient and can create dozens of mutants with far greater ease.”

A playful representation of a mitochondrion moving into a larger cell, bringing with it the "baggage" of mutated mitochondrial DNA. Researchers at the Salk Institute developed a new platform for studying that mutated mitochondrial DNA, helping explain the ways it influences human health. [Salk Institute]
A playful representation of a mitochondrion moving into a larger cell, bringing with it the “baggage” of mutated mitochondrial DNA. Researchers at the Salk Institute developed a new platform for studying that mutated mitochondrial DNA, helping explain the ways it influences human health. [Salk Institute]

The authors explained, “… we developed a scalable ES cell–based platform that integrates mtDNA mutagenesis, cybrid technology, high-sensitivity mutation detection, and optimized mouse transgenesis.” The platform starts with a protein, called mitochondrial DNA polymerase, generating randomly mutated mitochondrial DNA. That mutated mitochondrial DNA is then transferred into stem cells, which can be integrated with mouse embryos to create mice for study. Once one of these mice is established, researchers can investigate the specific symptoms of their specific mitochondrial DNA mutation and the mechanisms by which those symptoms arise—insight that can be used to design targeted therapies down the line. “Optimized ES cell–embryo aggregation enables robust contribution of mtDNA mutant ES cells to host embryos, producing chimeric mice with germline transmission,” the investigators noted.

Using this platform, the Salk team generated a library of 155 mitochondrial DNA mutation cell lines, each with its own distinct impact on mitochondrial performance. “Using this platform, we generate a library of 155 donor fibroblast lines carrying distinct homoplasmic single-nucleotide mtDNA mutations that produce diverse mitochondrial phenotypes, including impaired oxidative phosphorylation, increased reactive oxygen species, and altered mitochondrial membrane potential,” they stated. They then used that library to validate that the cells could be used to generate mice with single mitochondrial DNA mutations. These mice allowed them to find a strong correlation between mitochondrial function and early embryonic development, suggesting a baseline energy level is required for normal development.

“Our library is a huge milestone and is very diverse, with a scale of diversity similar to the known human disease-causing mutation diversity of around 260,” said Fan. “And with this collection of mutant cells, we can not only look at inherited mutations but also at ones that occur based on other stresses like environmental cues or aging.” The authors added, “Together, the advances outlined in this study establish a powerful and generalizable platform for systematically modeling the functional diversity of human mtDNA mutations and polymorphisms in vivo.”

The new platform and library are cracking open the world of mitochondrial DNA. With the ability to generate mitochondrial DNA mutants more rapidly, therapeutic development for mitochondrial disease and dysfunction will come more rapidly, too. The mouse models are already a huge step forward for the field, but the researchers are also eager to move into human models in a more human-relevant context.

“The majority of human diseases come with or cause mitochondrial dysfunction,” said Evans. “Progress in this field has been limited, but this new platform is going to fuel so much important research that points to therapeutic approaches to combat mitochondrial diseases, as well as diseases or conditions associated with mitochondrial dysfunction like cancer or aging.”

In their paper the team concluded, “The library provides a unique and comprehensive resource for modeling the diversity of human mtDNA variation in vitro and can also be used to generate in vivo models through ES-cybrid technology … By enabling the generation of both pathogenic and physiologically relevant mtDNA variants—including those resembling somatic mutations associated with aging and cancer—this platform substantially expands the toolkit available to mitochondrial researchers.”

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