GMOs could reboot chestnut trees

Under a slice-of-heaven sky, 150 acres of rolling green hills stretch off into the distance. About a dozen people—tree enthusiasts, conservationists, research biologists, biotech entrepreneurs, and a venture capitalist in long socks and a floppy hat—have driven to this rural spot in New York state on a perfect late-July day. 

We are here to see more than 2,500 transgenic chestnut seedlings at a seed farm belonging to American Castanea, a new biotech startup. The sprouts, no higher than our knees, are samples of likely the first genetically modified trees to be considered for federal regulatory approval as a tool for ecological restoration. American Castanea’s founders, and all the others here today, hope that the American chestnut (Castanea dentata) will be the first tree species ever brought back from functional extinction—but, ideally, not the last.

Living as long as a thousand years, the American chestnut tree once dominated parts of the Eastern forest canopy, with many Native American nations relying on them for food. But by 1950, the tree had largely succumbed to a fungal blight probably introduced by Japanese chestnuts. “Now after hard work, great ideas, and decades of innovation, we have a tree and a science platform designed to make restoration possible,” American Castanea cofounder Michael Bloom told the people squinting in the sun.

As recently as last year, it seemed the 35-year effort to revive the American chestnut might grind to a halt. Now, federal regulatory approval is expected soon. And there’s millions of dollars in new funding coming in from private investors and the federal government. One conservation nonprofit is in discussions with American Castanea to plant up to a million of its chestnuts per year as soon as they’re ready and approved. 

Nothing like this has ever been tried before. But the self-­proclaimed “nutheads” believe the reintroduction of a GMO, blight-resistant American chestnut at scale could also become a model for how environmentalists can redeploy trees in general: restoring forests and shifting food production, all to combat climate change and biodiversity loss. 

“It’s a hard time to be a tree,” says Leigh Greenwood, director of the forest pest and pathogen program at the Nature Conservancy, which has been supportive of the GMO chestnut’s regulatory application. “But there’s some really interesting promise and hope.”  

Four billion trees dead 

“Charismatic megafauna” is the scientific term for species, like pandas and blue whales, that draw a disproportionate amount of love and, thus, resources. The nearly vanished American chestnut may be the most charismatic tree east of the Rockies. Because of its historical importance, fast growth, and abundant productivity of both nuts and timber, it’s drawn an exceptional amount of interest among biologists, conservationists, and a new crop of farmers. 

Trees that die back from blight occasionally resprout. Volunteer groups like the American Chestnut Cooperators’ Foundation have been working for decades to gather and crossbreed wild trees in the hopes of nudging along natural resistance to the blight. Meanwhile, the State University of New York’s College of Environmental Science and Forestry (ESF), with the support of a different group, the American Chestnut Foundation (TACF), has been pursuing genetic engineering in its labs and on its 44 wooded acres outside Syracuse. 

When ESF biologist Bill Powell and his colleagues began working with chestnut embryonic cells in 1989, it took them a decade just to optimize the growing process to make research practical. After that, researchers in the small lab inserted a wheat gene in embryos that inactivated oxalic acid, the toxin produced by the blight fungus. Gathering results on these transgenic trees takes time, because each generation has to grow for a few years before it produces the most useful data. But they eventually created a promising line, named Darling-58 after Herb Darling, a New York construction magnate who funded this research through TACF. Darling-58 was not perfect, and results varied from tree to tree and site to site. But eventually, the data showed slower infections and smaller cankers, the bulbous growths produced by the blight. 

In 2020, Darling-58 became, in all likelihood, the first genetically modified forest tree to be submitted for federal regulatory approval to the US Department of Agriculture’s Animal and Plant Health Inspection Service, the EPA, and the FDA to determine the safety of introducing it in the wild. 

“It’s a hard time to be a tree. But there’s some really interesting promise and hope.”

It is this genetically engineered strain of chestnut that American Castanea, too, is now planting and propagating in New York state, under a nonexclusive commercial license from ESF. They want to sell these trees, pending approval. And then they want to keep going, engineering ever-better chestnuts, and selling them first to enthusiasts, then to farmers, and finally to conservationists for timber, reforestation, maybe even carbon capture. 

To aid the effort, the company is looking for extraordinary wild specimens. In early 2024, it purchased an orchard that had been lovingly cultivated for three decades by a conservationist. The windy hilltop spot houses hundreds of trees, collected like stray kittens from a dozen states throughout the chestnut’s natural range. 

Most of the trees are homely and sickly with blight. They have bulging cankers, “flagging” branches sporting yellow and brown leaves, or green shoots that burst each season from their large root systems only to flop over and die back. “They make me a little sad,” admits Andrew Serazin, cofounder of American Castanea. But a few have shot up as tall as 40 feet, with only a few cankers. All these specimens have been sampled and are being analyzed. They will become the basis of a chestnut gene database that’s as complete as American Castanea can make it. 

From there, the plan is: Apply bioinformatics and AI techniques to correlate genetic signatures with specific traits. Borrow techniques developed in the cannabis industry for seedling production, cloning, and growth acceleration in high-intensity light chambers—none of which have yet been yet applied at this scale to forest trees. Develop several diverse, improved new strains of chestnut that are blight-resistant and optimized for different uses like forest restoration, nut production, and timber. Then produce seedlings at a scale previously unknown. The hope is to accelerate restoration, cutting down the time it would take resistant strains of the tree to propagate in the wild. “Tree growth takes a long time. We need to bend the curve of something that’s like a 30-year problem,” says Serazin.

The breadtree revival

The chestnut has not disappeared from the US: In fact, Americans eat some 33 million pounds of the nuts a year. These are European and Asian varieties, mostly imported. But some companies are looking to expand the cultivation of the nuts domestically. 

Among those leading the quest is a company called Breadtree Farms in upstate New York, named for a traditional nickname for the chestnut. In March, it won a $2 million grant from the USDA to build the largest organic chestnut processing facility in the US. It will be up to eight times larger than needed for its own 250 acres of trees. The company is dedicated to scaling the regional industry. “We have a list of over 100 growers that are, and will be, planting chestnut trees,” says Russell Wallack, Breadtree’s young cofounder.

Chestnuts have a nutritional profile similar to brown rice; they’re high in carbohydrates and lower in fat than other nuts. And unlike other nut trees, the chestnut “masts”—produces a large crop—every year, making it far more prolific.

That makes it a good candidate for an alternative form of agriculture dubbed agroforestry, which incorporates more trees into food cultivation. Food, agriculture, and land use together account for about one-quarter of greenhouse-gas emissions. Adding trees, whether as windbreaks between fields or as crops, could lower the sector’s carbon footprint.

Many different trees can be used this way. But Joe Fargione, science director for the Nature Conservancy’s North America region, says the chestnut is a standout candidate. “It’s great from a climate perspective, and there’s a lot of farmers that are excited about it,” he says. “Chestnuts end up being big trees that store a lot of CO2 and have a product that can be very prolific. They have the potential to pay for themselves. We want not just environmental sustainability but economic sustainability.”

The passion for chestnut revival connects the foresters and the farmers. Farmers aren’t waiting for the GMO trees to get federal approval. They are planting existing Chinese varieties, and hybrids between American and Chinese chestnuts, which thrive in the East. Still, Fargione says that if nut cultivation is going to scale up, farmers will need reliable seed stock of genetically improved trees. 

A Tennessee family poses at the base of a chestnut tree, circa 1920. A deadly fungus nearly drove the once mighty species extinct by 1940.
NEGATIVES OF GREAT SMOKY MOUNTAINS NATIONAL PARK

On the other hand, those foreign orchard varieties would be considered invasives if planted in the wild. And they wouldn’t feed wildlife in the same way, says Sara Fern Fitzsimmons, chief conservation officer of the American Chestnut Foundation. “Wild turkeys prefer American chestnuts,” she says. “And the blue jay—since the American chestnut is smaller, he can fit more in his crop,” a food storage area inside a bird’s throat. For forest restoration you need American chestnuts or something as close to them as possible. That’s where the genetic engineering and crossbreeding projects will be crucial. But that path has been full of pitfalls.

Switched at birth

In late 2023, a biologist at the University of New England discovered evidence that Darling-58 was not what people thought it was. For nearly 10 years, all the data that ESF had painstakingly gathered on the strain actually pertained to a different line, Darling-54, which has its wheat gene in a different place on the genome. The promising results were all still there. The trees had simply been mislabeled that entire time. 

 A few weeks later, in December 2023, the American Chestnut Foundation suddenly announced it was withdrawing its support of ESF’s Darling tree research, citing the 54-58 mix-up, as well as what it called “disappointing performance results” for 54. 

But Andy Newhouse, director of the American Chestnut Project at SUNY ESF, says the mislabeling is not a deal-breaker. The research doesn’t “need to start from scratch,” he says. “This is correcting the record, making sure we have the appropriate label on it, and moving forward.” Newhouse says the regulatory application is ongoing (the USDA and FDA declined to comment on a pending regulatory application; the EPA did not respond to requests for comment). 

Newhouse defends the documented blight response of the trees that, we now know, are actually Darling-54.

And besides, he says, they’ve got a potentially better strain coming: the DarWin. The “Win” stands for “wound-inducible.” In these trees, the anti-blight action turns on—is induced—only when the tree’s bark is wounded, working something like an animal’s immune response. This could be more efficient than continuously expressing the anti-blight gene, the way Darling-54 does. So DarWin trees might reserve more of their energy to grow and produce nuts. 

The DarWin trees are about three years old, meaning data is still being collected. And if the Darling trees are approved for safety, it should smooth the path for a much faster approval of the DarWin trees, Newhouse says.

There was another reason, though, that TACF dropped its support of the Darling regulatory petition. In a FAQ on its website, the foundation said it was “surprised and concerned” that ESF had made a licensing deal for the Darling and DarWin trees—potentially worth millions—with a for-profit company: American Castanea.

TACF said it had been supporting the project under the assumption that the results would be available, for free, to anyone, in the “public commons.” Commercialization, it says, could make the trees more expensive for anyone who might want to plant them. Fitzsimmons wouldn’t comment further. 

The biotech boys

American Castanea’s Andrew Serazin is a Rhodes scholar whose scientific background is in tropical disease research. He rose in the ranks in global philanthropy, running million-­dollar grant competitions for the Gates Foundation, funding projects like vitamin-­enhanced “golden rice” and HIV vaccines. 

He was president of the Templeton World Charity Foundation in 2020 when it gave a “transformational” $3.2 million grant to SUNY ESF’s chestnut project. Serazin became convinced that the chestnut could be the seed of something much, much bigger. It didn’t hurt that he had a sentimental chestnut connection through his wife’s family farm in West Virginia, which dates back to the time of George Washington. 

With pests and pathogens threatening so many different species, “there’s a huge potential for there to be precision management of forests using all of the same capabilities we’ve used in human medicine,” he says. 

For that, Serazin was convinced, they needed money. Real money. Venture capital money. “I mean, really, there’s only one system that we know about that works the best for this kind of innovation, and that’s using incentives for companies to bring together these resources,” he says. 

Serazin teamed up with his friend Michael Bloom, an entrepreneur who’s sold two previous companies. They incorporated American Castanea for certification as a public benefit corporation in Delaware, pledging to balance profit with purpose and adhere to a high degree of transparency on social and environmental impact. They went to “impact investors” to sell the vision. That was part of what was going on at the seed farm on that July day; the company has $4 million in seed financing and wants to raise $7 million to $10 million more next year. 

What he’s offering investors, Serazin says, isn’t quick returns but a chance to “participate in the once-in-a-lifetime opportunity to bring back a tree species from functional extinction, and participate in this great American story.” 

What they’re proposing, over the next several decades or more, is no less than replanting the entire Eastern forest with a variety of genetically superior breeds, on the scale of millions of trees. 

It sounds, at first blush, like a sci-fi terraforming scenario. On the other hand, Leigh Greenwood, at the Nature Conservancy, says every species group of tree in the woods is threatened by climate change. Pathogens are emerging in new territories, trees are stressed by extreme weather, and the coldest winter temperatures, which used to reliably kill off all manner of forest insects and diseases at the edges of their habitats, are getting milder.

Besides chestnut blight, there’s Dutch elm disease, the emerald ash borer, butternut canker, oak wilt, and white pine blister rust. The southern pine beetle now ranges as far north as Massachusetts because of milder winters. The spongy (formerly gypsy) moth is a champion defoliator, munching enough leaves “to make an entire forest look naked in June,” says Greenwood. A new nematode that attacks leaves and buds, previously unknown to science, has emerged near the Great Lakes in the last decade. Sick and dying trees stop sequestering carbon and storing water, are prone to wildfire, and can take entire ecosystems down with them. 

“Invasive species are moving faster than biological time,” Greenwood says. “What we have to do is speed up the host trees, their natural selection. And that is an enormous task that only in very recent times have we really developed the tools in order to figure out how the heck we’re going to do that.” 

By “recent tools,” Greenwood means, more or less, what American Castanea is trying: genetic analysis and advanced horticultural techniques that allow resistant trees to be propagated and introduced into the wild more quickly. 

Greenwood is quick to say that the Nature Conservancy also supports the American Chestnut Cooperators’ Foundation, which crossbreeds wild American chestnuts for blight resistance. They are a small, all-volunteer organization with no university affiliation. They mail their crossbred chestnuts out to hobbyist landowners all over the country, and president Ed Greenwell tells me they don’t really know exactly how many are growing out there—maybe 5,000, maybe more. He has seen some that are big and healthy, he says. “We have many trees of 40-plus years of age.” 

What they don’t have is a sense of urgency. “We’re self-funded, so we could do our breeding as we choose,” says Greenwell. “Our method is tried and true, and we have no pressure to take shortcuts, like genetic modification, which theoretically could have shortened the time to get trees back in the woods.” 

The whole idea of a GMO forest tests our concept of what “nature” is. And that may just be a marker of where we are at this point in the Anthropocene.

Greenwell is not the only one to object to GMO chestnuts. In 2023, Joey Owle, then the secretary of agriculture and natural resources for the Eastern Band of Cherokee Indians, told Grist magazine that while the group was open to introducing transgenic trees on its land if necessary, it was the “last option that we would like to pursue.”

Greenwood led the writing of an expert letter, something like an amicus brief, in support of SUNY ESF’s regulatory petition for the Darling tree. She takes such objections seriously. “If we do not address the human dimensions of change, no matter how good the biological, chemical designs are,” she says, “those changes will fail.” 

That July day out at the seed farm, sitting under a tent with plates of pork barbecue, the scientists, conservationists, and businesspeople started debating how deep these GMO objections really run. Serazin said he believes that what people really hate is corporate monopoly, not the technology per se. “It’s really about the exertion of power and capital,” he said. He’s hoping that by incorporating as a public benefit corporation and making the trees widely available to conservation groups and responsible forest product and nut producers, he can convince people that American Castanea’s heart is in the right place. 

Still, others pointed out, the whole idea of a GMO forest tests our concept of what “nature” is. And that may just be a marker of where we are at this point in the Anthropocene—it’s hard to envision a future where any living creature in the ecological web can remain untouched by humans. 

That responsibility may connect us more to the past than we realize. For centuries, Native people like the Haudenosaunee Nation practiced intentional land management to improve habitat for the chestnut. When the Europeans began clearing land for farming and timber, the fast-growing tree was able to claim proportionately even more space for itself. It turns out the forest those colonists embraced—the forest dominated by chestnut trees—was no true accident of nature. It was a product of a relationship between people and chestnuts. One that continues to evolve today. 

Anya Kamenetz is a freelance reporter who writes the Substack newsletter The Golden Hour.

These companies are creating food out of thin air

Dried cells—it’s what’s for dinner. At least that’s what a new crop of biotech startups, armed with carbon-guzzling bacteria and plenty of capital, are hoping to convince us. Their claims sound too good to be true: They say they can make food out of thin air.

But that’s exactly how certain soil-dwelling bacteria work. In nature, these “autotrophic” microbes survive on a meager diet of oxygen, nitrogen, carbon dioxide, and water vapor drawn directly from the atmosphere. In the lab, they do the same, eating up waste carbon and reproducing so enthusiastically that their populations swell to fill massive fermentation tanks. Siphoned off and dehydrated, that bacterial biomass becomes a protein-rich powder that’s chock-full of nutrients and essentially infinitely renewable. 

Lisa Dyson is the founder of one of these startups, Air Protein. When she talks about the inspiration for her company, she often cites NASA research from the 1960s. Back then the agency, hoping to keep astronauts satiated on long-haul space journeys, explored the idea of growing bacterial cuisine on board before concluding, ultimately, that astronauts might not find it psychologically palatable. “Earth is actually like a spaceship,” Dyson explained in a 2016 TED Talk. “We have limited space and limited resources, and on Earth, we really do need to figure out how to recycle our carbon better.” Could these bacteria be the answer?

For now, the answer is a definite maybe. Some 25 companies worldwide have already taken up the challenge, hoping to turn abundant carbon dioxide into nutritious “air protein.” The ultimate goal of the people who work at these companies is to engineer a food source far lower in emissions than conventional farming—perhaps even one that could disrupt agriculture altogether. To do that, they’ll need to overcome some very real challenges. They’ll need to scale up production of their protein to compete commercially, and do it in a way that doesn’t create more emissions or other environmental issues. Even trickier: They’ll need to surmount the ick people may experience when contemplating a bacteria-based meal. 

Some of these companies are focused on industrial animal feed, fish meal, and pet food—products with slimmer profit margins but less exacting consumers and fewer regulatory hurdles. Human food, however, is where the real money—and impact—is. That’s why several companies, like Dyson’s Air Protein, are focused on it. In 2023 Air Protein opened its first “air farm” in San Leandro, California, a hub for the commercial food production industry, and announced a strategic development agreement with one of the largest agricultural commodity traders in the world, ADM, to collaborate on research and development and build an even larger, commercial-­scale plant. The company’s “Air Chicken” (which, to be clear, is not actual chicken) is slowly making its way toward grocery store shelves and dinner tables. But that’s only the beginning. Other companies are making progress at harnessing bacteria to spin air into protein, too—and someday soon, these microbial protein patties could be as common as veggie burgers. 

An alternative to alternative proteins

The environmental case for microbial protein is clear enough; it’s a simple calculus of arable land, energy, and mouths to feed. The global demand for protein is already at an all-time high, and with the population expected to grow to 9.7 billion by 2050, traditional agriculture will have a hard time keeping up, especially as it battles climate change, soil degradation, and disease. A growing global middle class is expected to raise levels of meat consumption, but factory-farmed meat is one of the leading drivers of greenhouse-­gas emissions. Although protein-rich alternatives like soy are far more sustainable, most of the soy grown in the world is destined for use as animal feed—not for human consumption. 

In contrast, bacterial “crops” convert carbon dioxide directly into protein, in a process that uses much less land and water. Microbial protein “farms” could operate year-round anywhere renewable electricity is cheap—even in places like Chile’s Atacama Desert, where farming is nearly impossible. That would take the strain off agricultural land—and potentially even give us the chance to return it to the wild. 

 “We are liberating food production from the constraints of agriculture,” Juha-Pekka Pitkänen, cofounder and CTO of the Finnish startup Solar Foods, explained in a recent company video. In April 2024 Solar Foods opened a demonstration factory in Vantaa, a short train ride from the Helsinki airport. It’s here, at Factory 01, that the company hopes to produce enough of its goldenrod-yellow protein powder, Solein, to prove itself viable—some 160 metric tons a year. 

Like Air Protein, Solar Foods begins its production process with naturally occurring hydrogen-­oxidizing bacteria that metabolize carbon dioxide, the way plants do. In sterile bioreactors similar to the fermentation vats used in the brewing industry, the bacteria flourish in water on a steady diet of CO2, hydrogen, and a few additional nutrients, like nitrogen, calcium, phosphorus, and potassium. As they multiply, the bacteria thicken the water into a slurry, which is continuously siphoned off and dehydrated, creating a protein-rich powder that can be used as an ingredient in alternative meats, dairy products, and snacks.

“We are liberating food production from the constraints of agriculture.”

Juha-Pekka Pitkänen, Solar Foods

As Pitkänen explains, his research team at Finland’s state-owned VTT Technical Research Centre knew these microorganisms existed in the wild. To find a viable candidate, they narrowed down the natural conditions where one might be found, and then—as is the Finnish way—put on some hiking boots and got out there. “In Finland, you don’t have to go very far to find nature,” he says, shrugging. “You can find something useful in a ditch.”

Still, not just any old ditch bacteria would do. Their target needed to both consume carbon dioxide and continue to thrive even after it was isolated from the microbial community it coexisted with, or competed against, in nature. “We were looking for a pacifist microorganism,” Pitkänen says. “It’s quite rare.” In a wet soil-dwelling bacterium of the genus Xanthobacter,they found their match: a nontoxic, lab-friendly microbe palatable enoughto slip into myriad food preparations.

At Solar Foods’ annual summer company party this year, their in-house chef served a bright-yellow lasagna made with Solein. The powder, Pitkänen says, makes an excellent flour for fresh pasta dough and works surprisingly well as a cream replacement in ice cream. It’s rich in carotenoids, so it can taste “carroty,” and it’s full of B12 and bioavailable iron, which makes it great for vegetarians. But the product isn’t a plug-and-play replacement for milk, eggs, or even meat. Rather, it’s an ingredient like any other, competing on nutritional value, cost, and texture. The company’s main competition, Pitkänen told me, isn’t other novel proteins—it’s soy meal. 

“In the last 10 years, the whole alternative-protein landscape has changed dramatically,” says Hannah Lester, an EU-based regulatory consultant to the novel-food industry. Soy patties and bean burgers are now ubiquitous to the point of being passé; today’s cutting-edge alternative proteins are cultivated from animal cells and coaxed from specially designed microorganisms using techniques originally developed to produce vaccines and other pharmaceuticals. “Molecular farmers” tend fields of bright-pink soybeans whose genetic makeup has been doctored so that they contain proteins identical to ones pigs make. “It’s really coming to the point where companies are utilizing the most incredible technology to produce food,” she says.

A fermentation process by any other name

The space Air Protein and Solar Foods occupy is so new that language hasn’t quite coalesced around it. Some in the alternative-protein industry evocatively call it “cellular agriculture,” but it’s also referred to as “gas fermentation,” emphasizing the process, and “biomass fermentation,” emphasizing the end product. These terms are distinct from “precision fermentation,” which refers to another buzzy bioprocess that employs genetically modified yeasts, other fungi, and bacteria to produce proteins indistinguishable from their animal-­derived counterparts. Precision fermentation isn’t a new technique: The US Food and Drug Administration approved its use to produce insulin in 1982, and 80% of the rennet used in cheese is now made this way, avoiding the need to harvest the enzymes from the stomach lining of calves. 

Rather than coaxing microorganisms to produce the animal-­derived proteins we’re already familiar with, companies like Air Protein and Solar Foods are proposing that we skip the intermediary and simply eat the microbes themselves, dried into a powder. Microbial biomass made with these new fermentation technologies is fibrous, vitamin-rich, and versatile. More important, these bacteria eat carbon, require very little land and water, and need no fossil-fuel-derived fertilizers. According to a life-cycle analysis produced by the University of Helsinki and the Natural Resources Institute Finland, microbial protein is between 53% and 100% more efficient to produce than animal protein.

Of course, that’s a wide range. Finland’s electricity mix favors renewables like hydropower and wind; in a country more reliant on fossil fuels, the environmental impact of making Solein, or any microbial protein, could be much higher. Growing microbes in bulk means creating the perfect conditions for them to thrive—and, as with any industrial production process, that requires factories, equipment, and power to run the entire system. It also requires a generous supply of elements like carbon dioxide and hydrogen. 

white cloud hovering over a sugar cone on blue sky background

ERIC MONGEON/MIT TECHNOLOGY REVIEW

Nearly all the world’s human-made hydrogen, a key element in the bacterial diet, comes from fossil-fuel production, and “green” hydrogen, which Solar Foods uses in its demonstration factory, comes from using renewable-powered electrolysis to split water, still an uncommon process. According to David Tze, CEO of the microbial-protein company NovoNutrients, which is currently working to branch out from industrial fish meal to human food, the segment of the microbial-protein industry powered by hydrogen is likely to set up shop wherever hydrogen is cheapest.

Carbon sources for this technology are likewise varied. If a company wants to use captured waste carbon, it will need to broker relationships with industries to connect its protein factories with those sources. Another alternative, sourcing carbon drawn from the atmosphere using direct air capture, or DAC, is still new, energy intensive, and expensive. For the time being, Air Protein uses the same commercially available carbon dioxide used in sparkling water, and while Solar Foods uses DAC for about 15% of the carbon it needs at its demonstration factory, the rest is sourced commercially. Both companies hope to adjust their carbon sources as they scale, and as DAC becomes more commercially available. 

Even if the bacteria were fed a diet of entirely captured carbon, they wouldn’t be permanently removing it from the atmosphere, since we release carbon when we digest food. Still, Tze says, “we’re giving a second life to CO2, and allowing it to add so much more positive value to the economy.” More important, the bacteria-based products drastically reduce the emissions footprint of protein. According to a 2016 study by the World Resources Institute, producing a single ton of beef creates around 2,400 metric tons of greenhouse-gas emissions. For plant-based sources of protein, like pulses, the number is much less than 300—but for microbial proteins it may ultimately be in the single digits. “If someone can eat a bite of our product instead of a bite of anything else,” Tze says, “it could be one or three orders of magnitude difference.”

Of course, none of this works if microbial protein remains a niche industry, or if the product is too expensive for the average consumer. Even running at capacity, Solar Foods’ demonstration factory can only produce enough protein to provide the entire population of Finland with one meal a year. From a business standpoint, Pitkänen says, that’s good news: There’s plenty of room to grow. But if they hope to make a dent in the long-term sustainability of our food systems, companies like Solar Foods and Air Protein will need to scale up by orders of magnitude too. It remains to be seen if they will be able to meet that challenge—and if consumers will be ready. 

Even though both the process (fermentation) and the material (living microorganisms) are as natural as the world and as old as time, the idea of whipping air and microbes together to make dinner will strike many people as unthinkably weird. Food is cultural, after all—and especially in the US, protein is political. In interviews, Dyson takes pains to call the bacteria behind Air Protein’s process “cultures,” emphasizing the connection to traditional fermented foods like yogurt, beer, or miso. On the Solar Foods website, chic people drink yellow Solein smoothies at tasteful Nordic tables. No bacteria are pictured.

Solar Foods is still awaiting final regulatory approval in the EU and the US, but Solein is already for sale in Singapore, where it’s been whipped into chocolate gelato and hazelnut-­strawberry snack bars. If Singaporeans took issue with eating powdered bacteria, they made little show of it. When it comes to food biotechnology, the most progressive countries in the world are those with the least arable land. Singapore, which imports nearly everything, hopes to meet 30% of its own nutritional needs by 2030. Israel, a semi-arid country with limited landmass, has invested heavily in biomanufacturing, as has the Netherlands, where farmland has been heavily depleted by chemical fertilizers. But even in less constrained countries, “agriculture is on its knees because of climate change,” says Lester, the regulatory expert. “At some point, sadly, we’re just not going to be able to produce food in the traditional way. We do need alternatives. We need government support. We need fundamental policy change in how we fund food.”

This sentiment seems to be resonating in the United States. In September 2022, President Joe Biden signed an executive order to advance biomanufacturing by expanding training, streamlining regulation, and bolstering federal investment in biotechnology R&D, specifically citing “boost[ing] sustainable biomass production” as a key objective. In 2021, the Defense Advanced Research Projects Agency launched the Cornucopia program, asking four research teams—one of which includes Dyson’s company, Air Protein—to create a complete nutrition system, small enough to fit on a Humvee, that can harvest nitrogen and carbon from the air and use it to produce microbial rations in the form of shakes, bars, gels, and jerky. Microbial protein may never be deployed on long-haul space trips as NASA dreams, but it seems that the government is betting it could keep us alive on Spaceship Earth—that is, if the crew doesn’t reject it outright.

Claire L. Evans is a writer and musician exploring ecology, technology, and culture.

Two Nobel Prize winners want to cancel their own CRISPR patents in Europe

In the decade-long fight to control CRISPR, the super-tool for modifying DNA, it’s been common for lawyers to try to overturn patents held by competitors by pointing out errors or inconsistencies.

But now, in a surprise twist, the team that earned the Nobel Prize in chemistry for developing CRISPR is asking to cancel two of their own seminal patents, MIT Technology Review has learned. The decision could affect who gets to collect the lucrative licensing fees on using the technology.

­­The request to withdraw the pair of European patents, by lawyers for Nobelists Emmanuelle Charpentier and Jennifer Doudna, comes after a damaging August opinion from a European technical appeals board, which ruled that the duo’s earliest patent filing didn’t explain CRISPR well enough for other scientists to use it and doesn’t count as a proper invention.

The Nobel laureates’ lawyers say the decision is so wrong and unfair that they have no choice but to preemptively cancel their patents, a scorched-earth tactic whose aim is to prevent the unfavorable legal finding from being recorded as the reason. 

“They are trying to avoid the decision by running away from it,” says Christoph Then, founder of Testbiotech, a German nonprofit that is among those opposing the patents, who provided a copy of the technical opinion and response letter to MIT Technology Review. “We think these are some of the earliest patents and the basis of their licenses.”

Discovery of the century

CRISPR has been called the biggest biotech discovery of the century, and the battle to control its commercial applications—such as gene-altered plants, modified mice, and new medical treatments—has raged for a decade.

The dispute primarily pits Charpentier and Doudna, who were honored with the Nobel Prize in 2020 for developing the method of genome editing, against Feng Zhang, a researcher at the Broad Institute of MIT and Harvard, who claimed to have invented the tool first on his own.

Back in 2014, the Broad Institute carried out a coup de main when it managed to win, and later defend, the controlling US patent on CRISPR’s main uses. But the Nobel pair could, and often did, point to their European patents as bright points in their fight. In 2017, the University of California, Berkeley, where Doudna works, touted its first European patent as exciting, “broad,” and “precedent” setting.

After all, a region representing more than 30 countries had not only recognized the pair’s pioneering discovery; it had set a standard for other patent offices around the world. It also made the US Patent Office look like an outlier whose decisions favoring the Broad Institute might not hold up long term. A further appeal challenging the US decisions is pending in federal court.

Long-running saga

But now the European Patent Office is also saying—for different reasons—that Doudna and Charpentier can’t claim their basic invention. And that’s a finding their attorneys think is so damaging, and reached in such an unjust way, that they have no choice but to sacrifice their own patents. “The Patentees cannot be expected to expose the Nobel-prize winning invention … to the repercussions of a decision handed down under such circumstances,” says the 76page letter sent by German attorneys on their behalf on September 20.

The chief intellectual-property attorney at the University of California, Randi Jenkins, confirmed the plan to revoke the two patents but downplayed their importance. 

“These two European patents are just another chapter in this long-running saga involving CRISPR-Cas9,” Jenkins said. “We will continue pursuing claims in Europe, and we expect those ongoing claims to have meaningful breadth and depth of coverage.”

The patents being voluntarily disavowed are EP2800811, granted in 2017, and EP3401400, granted in 2019. Jenkins added the Nobelists still share one issued CRISPR patent in Europe, EP3597749, and one that is pending. That tally doesn’t include a thicket of patent claims covering more recent research from Doudna’s Berkeley lab that were filed separately.

Freedom to operate

The cancellation of the European patents will affect a broad network of biotech companies that have bought and sold rights as they seek to achieve either commercial exclusivity to new medical treatments or what’s called “freedom to operate”—the right to pursue gene-slicing research unmolested by doubts over who really owns the technique. 

These companies include Editas Medicine, allied with the Broad Institute; Caribou Biosciences and Intellia Therapeutics in the US, both cofounded by Doudna; and Charpentier’s companies, CRISPR Therapeutics and ERS Genomics.

ERS Genomics, which is based in Dublin and calls itself “the CRISPR licensing company,” was set up in Europe specifically to collect fees from others using CRISPR. It claims to have sold nonexclusive access to its “foundational patents” to more than 150 companies, universities, and organizations who use CRISPR in their labs, manufacturing, or research products.

For example, earlier this year Laura Koivusalo, founder of a small Finnish biotech company, StemSight, agreed to a “standard fee” because her company is researching an eye treatment using stem cells that were previously edited using CRISPR.

Although not every biotech company thinks it’s necessary to pay for patent rights long before it even has a product to sell, Koivusalo decided it would be the right thing to do. “The reason we got the license was the Nordic mentality of being super honest. We asked them if we needed a license to do research, and they said yes, we did,” she says.

A slide deck from ERS available online lists the fee for small startups like hers at $15,000 a year. Koivusalo says she agreed to buy a license to the same two patents that are now being canceled. She adds: “I was not aware they were revoked. I would have expected them to give a heads-up.” 

A spokesperson for ERS Genomics said its customers still have coverage in Europe based on the Nobelists’ remaining CRISPR patent and pending application.

In the US, the Broad Institute has also been selling licenses to use CRISPR. And the fees can get big if there’s an actual product involved. That was the case last year, when Vertex Pharmaceuticals won approval to sell the first CRISPR-based treatment, for sickle-cell disease. To acquire rights under the Broad Institute’s CRISPR patents, Vertex agreed to pay $50 million on the barrelhead—and millions more in the future.

PAM problem

There’s no doubt that Charpentier and Doudna were first to publish, in a 2012 paper, how CRISPR can function as a “programmable” means of editing DNA. And their patents in Europe withstood an initial round of formal oppositions filed by lawyers.

But this August, in a separate analysis, a technical body decided that Berkeley had omitted a key detail from its earliest patent application, making it so that “the skilled person could not carry out the claimed method,” according to the finding. That is, it said, the invention wasn’t fully described or enabled.

The omission relates to a feature of DNA molecules called “protospacer adjacent motifs,” or PAMs. These features, a bit like runway landing lights, determine at what general locations in a genome the CRISPR gene scissors are able to land and make cuts, and where they can’t.

In the 76-page reply letter sent by lawyers for the Nobelists, they argue there wasn’t really any need to mention these sites, which they say were so obvious that “even undergraduate students” would have known they were needed. 

The lengthy letter leaves no doubt the Nobel team feels they’ve been wronged. In addition to disavowing the patents, the text runs on because it seeks to “make of public record the reasons for which we strongly disagree with [the] assessment on all points” and to “clearly show the incorrectness” of the decision, which, they say, “fails to recognize the nature and origin of the invention, misinterprets the common general knowledge, and additionally applies incorrect legal standards.”

A new smart mask analyzes your breath to monitor your health

Your breath can give away a lot about you. Each exhalation contains all sorts of compounds, including possible biomarkers for disease or lung conditions, that could give doctors a valuable insight into your health.

Now a new smart mask, developed by a team at the California Institute of Technology, could help doctors check your breath for these signals continuously and in a noninvasive way. A patient could wear the mask at home, measure their own levels, and then go to the doctor if a flare-up is likely. 

“They don’t have to come to the clinic to assess their inflammation level,” says Wei Gao, professor of Medical Engineering at Caltech and one of the smart mask’s creators. “This can be lifesaving.”

The smart mask, details of which were published in Science today, uses a two-part cooling system to chill the breath of its wearer. The cooling turns the breath into exhaled breath condensate (EBC). 

EBC, essentially a liquid version of someone’s breath, is easier to analyze, because biomarkers like nitrite and alcohol content are more concentrated in a liquid than in a gas. The mask design takes inspiration from plants’ capillary abilities, using a series of microfluidic modules that create pressure to push the EBC fluid around to sensors in the mask.

The sensors are connected via Bluetooth to a device like a phone, where the patient has access to real-time health readings.

“The biggest challenge has always been collecting real-time samples. This problem has been solved. That’s a paradigm shift,” says Rajan Chakrabarty, professor of Environmental and Chemical Engineering at Washington University in St. Louis and who was not involved in the research.

The Caltech team tested the smart mask with patients, including several who had chronic obstructive pulmonary disease (COPD) or asthma or had just gotten over a covid-19 infection. They were testing the masks for comfort and breathability, but they also wanted to see if the masks actually worked at tracking useful biomarkers throughout a patient’s daily activities, such as exercise and work. 

The mask picked up on higher levels of nitrite in patients who had asthma or other conditions that involved inflamed airways. It also picked up on higher alcohol content after a patient went out drinking, which demonstrates another potential application of the mask. Analyzing breath this way is more accurate than the typical breathalyzer test, which involves a patient blowing into a device. Blowing can produce imprecise results due to alcohol in saliva being spit out.

The researchers hope this is just the beginning. They plan to test the masks on a larger population, and if all goes well, commercialize the masks to get them out to a wider audience. They hope the mask will be a platform for broader application, where sensors for a range of biomarkers could be slotted in and out. 

“What I would like to be able to do is take off their sensors, put in my sensors, and this becomes the building block for doing all other types of development,” says Albert Titus, professor and chair of the Department of Biomedical Engineering at the University at Buffalo and who wasn’t part of the Caltech team. “That’s where I’d like to see it go.”

For example, there may be the possibility to measure ketones in the breath, a high level of which is a sign of diabetes, or glucose levels, to help people with diabetes monitor their condition.

“The mask can be reconfigured for many different applications,” says Gao.

This researcher wants to replace your brain, little by little

A US agency pursuing moonshot health breakthroughs has hired a researcher advocating an extremely radical plan for defeating death.

His idea? Replace your body parts. All of them. Even your brain. 

Jean Hébert, a new hire with the US Advanced Projects Agency for Health (ARPA-H), is expected to lead a major new initiative around “functional brain tissue replacement,” the idea of adding youthful tissue to people’s brains. 

President Joe Biden created ARPA-H in 2022, as an agency within the Department of Health and Human Services, to pursue what he called  “bold, urgent innovation” with transformative potential. 

The brain renewal concept could have applications such as treating stroke victims, who lose areas of brain function. But Hébert, a biologist at the Albert Einstein school of medicine, has most often proposed total brain replacement, along with replacing other parts of our anatomy, as the only plausible means of avoiding death from old age.

As he described in his 2020 book, Replacing Aging, Hébert thinks that to live indefinitely people must find a way to substitute all their body parts with young ones, much like a high-mileage car is kept going with new struts and spark plugs.

The idea has a halo of plausibility since there are already liver transplants and titanium hips, artificial corneas and substitute heart valves. The trickiest part is your brain. That ages, too, shrinking dramatically in old age. But you don’t want to swap it out for another—because it is you.

And that’s where Hébert’s research comes in. He’s been exploring ways to “progressively” replace a brain by adding bits of youthful tissue made in a lab. The process would have to be done slowly enough, in steps, that your brain could adapt, relocating memories and your self-identity.  

During a visit this spring to his lab at Albert Einstein, Hébert showed MIT Technology Review how he has been carrying out initial experiments with mice, removing small sections of their brains and injecting slurries of embryonic cells. It’s a step toward proving whether such youthful tissue can survive and take over important functions.

To be sure, the strategy is not widely accepted, even among researchers in the aging field. “On the surface it sounds completely insane, but I was surprised how good a case he could make for it,” says Matthew Scholz, CEO of aging research company Oisín Biotechnologies, who met with Hébert this year. 

Scholz is still skeptical though. “A new brain is not going to be a popular item,” he says. “The surgical element of it is going to be very severe, no matter how you slice it.”

Now, though, Hébert’s ideas appear to have gotten a huge endorsement from the US government. Hébert told MIT Technology Review that he had proposed a $110 million project to ARPA-H to prove his ideas in monkeys and other animals, and that the government “didn’t blink” at the figure. 

ARPA-H confirmed this week that it had hired Hébert as a program manager. 

The agency, modeled on DARPA, the Department of Defense organization that developed stealth fighters, gives managers unprecedented leeway in awarding contracts to develop novel technologies. Among its first programs are efforts to develop at-home cancer tests and cure blindness with eye transplants.

President Biden created ARPA-H in 2022 to pursue “bold, urgent innovation” with transformative potential.

It may be several months before details of the new project are announced, and it’s possible that ARPA-H will establish more conventional goals like treating stroke victims and Alzheimer’s patients, whose brains are damaged, rather than the more radical idea of extreme life extension. 

If it can work, forget aging; it would be useful for all kinds of neurodegenerative disease,” says Justin Rebo, a longevity scientist and entrepreneur.

But defeating death is Hébert’s stated aim. “I was a weird kid and when I found out that we all fall apart and die, I was like, ‘Why is everybody okay with this?’ And that has pretty much guided everything I do,” he says. “I just prefer life over this slow degradation into nonexistence that biology has planned for all of us.”

Hébert, now 58, also recalls when he began thinking that the human form might not be set in stone. It was upon seeing the 1973 movie Westworld, in which the gun-slinging villain, played by Yul Brynner, turns out to be an android. “That really stuck with me,” Hébert said.

Lately, Hébert has become something of a star figure among immortalists, a fringe community devoted to never dying. That’s because he’s an established scientist who is willing to propose extreme steps to avoid death. “A lot of people want radical life extension without a radical approach. People want to take a pill, and that’s not going to happen,” says Kai Micah Mills, who runs a company, Cryopets, developing ways to deep-freeze cats and dogs for future reanimation.

The reason pharmaceuticals won’t ever stop aging, Hébert says, is that time affects all of our organs and cells and even degrades substances such as elastin, one of the molecular glues that holds our bodies together. So even if, say, gene therapy could rejuvenate the DNA inside cells, a concept some companies are exploring, Hébert believes we’re still doomed as the scaffolding around them comes undone.

One organization promoting Hébert’s ideas is the Longevity Biotech Fellowship (LBF), a self-described group of “hardcore” life extension enthusiasts, which this year published a technical roadmap for defeating aging altogether. In it, they used data from Hébert’s ARPA-H proposal to argue in favor of extending life with gradual brain replacement for elderly subjects, as well as transplant of their heads onto the bodies of “non-sentient” human clones, raised to lack a functioning brain of their own, a procedure they referred to as “body transplant.”

Such a startling feat would involve several technologies that don’t yet exist, including a means to attach a transplanted head to a spinal cord. Even so, the group rates “replacement” as the most likely way to conquer death, claiming it would take only 10 years and $3.6 billion to demonstrate.

“It doesn’t require you to understand aging,” says Mark Hamalainen, co-founder of the research and education group. “That is why Jean’s work is interesting.”

Hébert’s connections to such far-out concepts (he serves as a mentor in LBF’s training sessions) could make him an edgy choice for ARPA-H, a young agency whose budget is $1.5 billion a year.

For instance, Hebert recently said on a podcast with Hamalainen that human fetuses might be used as a potential source of life-extending parts for elderly people. That would be ethical to do, Hébert said during the program, if the fetus is young enough that there “are no neurons, no sentience, and no person.” And according to a meeting agenda viewed by MIT Technology Review, Hébert was also a featured speaker at an online pitch session held last year on full “body replacement,” which included biohackers and an expert in primate cloning.

Hébert declined to describe the session, which he said was not recorded “out of respect for those who preferred discretion.” But he’s in favor of growing non-sentient human bodies. “I am in conversation with all these groups because, you know, not only is my brain slowly deteriorating, but so is the rest of my body,” says Hébert. “I’m going to need other body parts as well.”

The focus of Hébert’s own scientific work is the neocortex, the outer part of the brain that looks like a pile of extra-thick noodles and which houses most of our senses, reasoning, and memory. The neocortex is “arguably the most important part of who we are as individuals,” says Hébert, as well as “maybe the most complex structure in the world.”

There are two reasons he believes the neocortex could be replaced, albeit only slowly. The first is evidence from rare cases of benign brain tumors, like a man described in the medical literature who developed a growth the size of an orange. Yet because it grew very slowly, the man’s brain was able to adjust, shifting memories elsewhere, and his behavior and speech never seemed to change—even when the tumor was removed. 

That’s proof, Hébert thinks, that replacing the neocortex little by little could be achieved “without losing the information encoded in it” such as a person’s self-identity.

The second source of hope, he says, is experiments showing that fetal-stage cells can survive, and even function, when transplanted into the brains of adults. For instance, medical tests underway are showing that young neurons can integrate into the brains of people who have epilepsy  and stop their seizures.  

“It was these two things together—the plastic nature of brains and the ability to add new tissue—that, to me, were like, ‘Ah, now there has got to be a way,’” says Hébert.

“I just prefer life over this slow degradation into nonexistence that biology has planned for all of us.”

One challenge ahead is how to manufacture the replacement brain bits, or what Hebert has called “facsimiles” of neocortical tissue. During a visit to his lab at Albert Einstein, Hébert described plans to manually assemble chunks of youthful brain tissue using stem cells. These parts, he says, would not be fully developed, but instead be similar to what’s found in a still-developing fetal brain. That way, upon transplant, they’d be able to finish maturing, integrate into your brain, and be “ready to absorb and learn your information.”

To design the youthful bits of neocortex, Hébert has been studying brains of aborted human fetuses 5 to 8 weeks of age. He’s been measuring what cells are present, and in what numbers and locations, to try to guide the manufacture of similar structures in the lab.

“What we’re engineering is a fetal-like neocortical tissue that has all the cell types and structure needed to develop into normal tissue on its own,” says Hébert. 

Part of the work has been carried out by a startup company, BE Therapeutics (it stands for Brain Engineering), located in a suite on Einstein’s campus and which is funded by Apollo Health Ventures, VitaDAO, and with contributions from a New York State development fund. The company had only two employees when MIT Technology Review visited this spring, and the its future is uncertain, says Hébert, now that he’s joining ARPA-H and closing his lab at Einstein.

Because it’s often challenging to manufacture even a single cell type from stem cells, making a facsimile of the neocortex involving a dozen cell types isn’t an easy project. In fact, it’s just one of several scientific problems standing between you and a younger brain, some of which might never have practical solutions. “There is a saying in engineering. You are allowed one miracle, but if you need more than one, find another plan,” says Scholz.

Maybe the crucial unknown is whether young bits of neocortex will ever correctly function inside an elderly person’s brain, for example by establishing connections or storing and sending electro-chemical information. Despite evidence the brain can incorporate individual transplanted cells, that’s never been robustly proven for larger bits of tissue, says Rusty Gage, a biologist at the Salk Institute in La Jolla, Calif., and who is considered a pioneer of neural transplants. He says researchers for years have tried to transplant larger parts of fetal animal brains into adult animals, but with inconclusive results. “If it worked, we’d all be doing more of it,” he says.

The problem, says Gage, isn’t whether the tissue can survive, but whether it can participate in the workings of an existing brain. “I am not dissing his hypothesis. But that’s all it is,” says Gage. “Yes, fetal or embryonic tissue can mature in the adult brain. But whether it replaces the function of the dysfunctional area is an experiment he needs to do, if he wants to convince the world he has actually replaced an aged section with a new section.”

In his new role at ARPA-H, it’s expected that Hébert will have a large budget to fund scientists to try and prove his ideas can work. He agrees it won’t be easy. “We’re, you know, a couple steps away from reversing brain aging,” says Hébert. “A couple of big steps away, I should say.”

What’s next for MDMA

MIT Technology Review’s What’s Next series looks across industries, trends, and technologies to give you a first look at the future. You can read the rest of them here.

MDMA, sometimes called Molly or ecstasy, has been banned in the United States for more than three decades. Now this potent mind-altering drug is poised to become a badly needed therapy for PTSD.

On June 4, the Food and Drug Administration’s advisory committee will meet to discuss the risks and benefits of MDMA therapy. If the committee votes in favor of the drug, it could be approved to treat PTSD this summer. The approval would represent a momentous achievement for proponents of mind-altering drugs, who have been working toward this goal for decades. And it could help pave the way for FDA approval of other illicit drugs like psilocybin. But the details surrounding how these compounds will make the transition from illicit substances to legitimate therapies are still foggy. 

Here’s what to know ahead of the upcoming hearing. 

What’s the argument for legitimizing MDMA? 

Studies suggest the compound can help treat mental-health disorders like PTSD and depression. Lykos, the company that has been developing MDMA as a therapy, looked at efficacy in two clinical trials that included about 200 people with PTSD. Researchers randomly assigned participants to receive psychotherapy with or without MDMA. The group that received MDMA-assisted therapy had a greater reduction in PTSD symptoms. They were also more likely to respond to treatment, to meet the criteria for PTSD remission, and to lose their diagnosis of PTSD.

But some experts question the validity of the results. With substances like MDMA, study participants almost always know whether they’ve received the drug or a placebo. That can skew the results, especially when the participants and therapists strongly believe a drug is going to help. The Institute for Clinical and Economic Review (ICER), a nonprofit research organization that evaluates the clinical and economic value of drugs, recently rated the evidence for MDMA-assisted therapy as “insufficient.

In briefing documents published ahead of the June 4 meeting, FDA officials write that the question of approving MDMA “presents a number of complex review issues.”

The ICER report also referenced allegations of misconduct and ethical violations. Lykos (formerly the Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation) acknowledges that ethical violations occurred in one particularly high-profile case. But in a rebuttal to the ICER report, more than 70 researchers involved in the trials wrote that “a number of assertions in the ICER report represent hearsay, and should be weighted accordingly.” Lykos did not respond to an interview request.

At the meeting on the 4th, the FDA has asked experts to discuss whether Lykos has demonstrated that MDMA is effective, whether the drug’s effect lasts, and what role psychotherapy plays. The committee will also discuss safety, including the drug’s potential for abuse and the risk posed by the impairment MDMA causes. 

What’s stopping people from using this therapy?

MDMA is illegal. In 1985, the Drug Enforcement Agency grew concerned about growing street use of the drug and added it to its list of Schedule 1 substances—those with a high abuse potential and no accepted medical use. 

MDMA boosts the brain’s production of feel-good neurotransmitters, causing a burst of euphoria and good will toward others. But the drug can also cause high blood pressure, memory problems, anxiety, irritability, and confusion. And repeated use can cause lasting changes in the brain

If the FDA approves MDMA therapy, when will people be able to access it?

That has yet to be determined. It could take months for the DEA to reclassify the drug. After that, it’s up to individual states. 

Lykos applied for approval of MDMA-assisted therapy, not just the compound itself. In the clinical trials, MDMA administration happened in the presence of licensed therapists, who then helped patients process their emotions during therapy sessions that lasted for hours.

But regulating therapy isn’t part of the FDA’s purview. The FDA approves drugs; it doesn’t oversee how they’re administered. “The agency has been clear with us,” says Kabir Nath, CEO of Compass Pathways, the company working to bring psilocybin to market. “They don’t want to regulate psychotherapy, because they see that as the practice of medicine, and that’s not their job.” 

However, for drugs that carry a risk of serious side effects, the FDA can add a risk evaluation and mitigation strategy to its approval. For MDMA that might include mandating that the health-care professionals who administer the medication have certain certifications or specialized training, or requiring that the drug be dispensed only in licensed facilities. 

For example, Spravato, a nasal spray approved in 2019 for depression that works much like ketamine, is available only at a limited number of health-care facilities and must be taken under the observation of a health-care provider. Having safeguards in place for MDMA makes sense, at least at the outset, says Matt Lamkin, an associate professor at the University of Tulsa College of Law who has been following the field closely.: “Given the history, I think it would only take a couple of high-profile bad incidents to potentially set things back.”

What mind-altering drug is next in line for FDA approval?

Psilocybin, a.k.a. the active ingredient in magic mushrooms. This summer Compass Pathways will release the first results from one of its phase 3 trials of psilocybin to treat depression. Results from the other trial will come in the middle of 2025, which—if all goes well—puts the company on track to file for approval in the fall or winter of next year. With the FDA review and the DEA rescheduling, “it’s still kind of two to three years out,” Nath says.

Some states are moving ahead without formal approval. Oregon voters made psilocybin legal in 2020, and the drug is now accessible there at about 20 licensed centers for supervised use. “It’s an adult use program that has a therapeutic element,” says Ismail Ali, director of policy and advocacy at the Multidisciplinary Association for Psychedelic Studies (MAPS).

Colorado voted to legalize psilocybin and some other plant-based psychedelics in 2022, and the state is now working to develop a framework to guide the licensing of facilitators to administer these drugs for therapeutic purposes. More states could follow. 

So would FDA approval of these compounds open the door to legal recreational use of psychedelics?

Maybe. The DEA can still prosecute physicians if they’re prescribing drugs outside of their medically accepted uses. But Lamkin does see the lines between recreational use and medical use getting blurry. “What we’re seeing is that the therapeutic uses have recreational side effects and the recreation has therapeutic side effects,” he says. “I’m interested to see how long they can keep the genie in the bottle.”

What’s the status of MDMA therapies elsewhere in the world? 

Last summer, Australia became the first country to approve MDMA and psilocybin as medicines to treat psychiatric disorders, but the therapies are not yet widely available. The first clinic opened just a few months ago. The US is poised to become the second country if the FDA greenlights Lykos’s application. Health Canada told the CBC it is watching the FDA’s review of MDMA “with interest.” Europe is lagging a bit behind, but there are some signs of movement. In April, the European Medicines Agency convened a workshop to bring together a variety of stakeholders to discuss a regulatory framework for psychedelics.

Splashy breakthroughs are exciting, but people with spinal cord injuries need more

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 an external stimulator that delivers electrical pulses to the spine to help improve hand and arm function in people who are paralyzed. This isn’t a cure. In many cases the gains were relatively modest. One participant said it increased his typing speed from 23 words a minute to 35. Another participant was newly able to use scissors with his right hand. A third used her left hand to release a seatbelt.

The study didn’t garner as much media attention as previous, much smaller studies that focused on helping people with paralysis walk. Tech that allows people to type slightly faster or put their hair in a ponytail unaided just doesn’t have the same allure. “The image of a paralyzed person getting up and walking is almost biblical,” Charles Liu, director of the Neurorestoration Center at the University of Southern California, once told a reporter. 

For the people who have spinal cord injuries, however, incremental gains can have a huge impact on quality of life. 

So today in The Checkup, let’s talk about this tech and who it serves.

In 2004, Kim Anderson-Erisman, a researcher at Case Western Reserve University, who also happens to be paralyzed, surveyed more than 600 people with spinal cord injuries. Wanting to better understand their priorities, she asked them to consider seven different functions—everything from hand and arm mobility to bowel and bladder function to sexual function. She asked respondents to rank these functions according to how big an impact recovery would have on their quality of life. 

Walking was one of the functions, but it wasn’t the top priority for most people. Most quadriplegics put hand and arm function at the top of the list. For paraplegics, meanwhile, the top priority was sexual function. I interviewed Anderson-Erisman for a story I wrote in 2019 about research on implantable stimulators as a way to help people with spinal cord injuries walk. For many people, “not being able to walk is the easy part of spinal cord injury,” she told me. “[If] you don’t have enough upper-extremity strength or ability to take care of yourself independently, that’s a bigger problem than not being able to walk.” 

One of the research groups I focused on was at the University of Louisville. When I visited in 2019, the team had recently made the news because two people with spinal cord injuries in one of their studies had regained the ability to walk, thanks to an implanted stimulator. “Experimental device helps paralyzed man walk the length of four football fields,” one headline had trumpeted.

But when I visited one of those participants, Jeff Marquis, in his condo in Louisville, I learned that walking was something he could only do in the lab. To walk he needed to hold onto parallel bars supported by other people and wear a harness to catch him if he fell. Even if he had extra help at home, there wasn’t enough room for the apparatus. Instead, he gets around his condo the same way he gets around outside his condo: in a wheelchair. Marquis does stand at home, but even that requires a bulky frame. And the standing he does is only for therapy. “I mostly just watch TV while I’m doing that,” he said.  

That’s not to say the tech has been useless. The implant helped Marquis gain some balance, stamina, and trunk stability. “Trunk stability is kind of underrated in how much easier that makes every other activity I do,” he told me. “That’s the biggest thing that stays with me when I have [the stimulator] turned off.”  

What’s exciting to me about this latest study is that the tech gave the participants skills they could use beyond the lab. And because the stimulator is external, it is likely to be more accessible and vastly cheaper. Yes, the newly enabled movements are small, but if you listen to the palpable excitement of one study participant as he demonstrates how he can move a small ball into a cup, you’ll appreciate that incremental gains are far from insignificant. That’s according to Melanie Reid, one of the participants in the latest trial, who spoke at a press conference last week. “There [are] no miracles in spinal injury, but tiny gains can be life-changing.”


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive

In 2017, we hailed as a breakthrough technology electronic interfaces designed to reverse paralysis by reconnecting the brain and body. Antonio Regalado has the story

An implanted stimulator changed John Mumford’s life, allowing him to once again grasp objects after a spinal cord injury left him paralyzed. But when the company that made the device folded, Mumford was left with few options for keeping the device running. “Limp limbs can be reanimated by technology, but they can be quieted again by basic market economics,” wrote Brian Bergstein in 2015. 

In 2014, Courtney Humphries covered some of the rat research that laid the foundation for the technological developments that have allowed paralyzed people to walk. 

From around the web

Lots of bird flu news this week. A second person in the US has tested positive for the illness after working with infected livestock. (NBC)

The livestock industry, which depends on shipping tens of millions of live animals, provides some ideal conditions for the spread of pathogens, including bird flu. (NYT)

Long read: How the death of a nine-year-old boy in Cambodia triggered a global H5N1 alert. (NYT)

You’ve heard about tracking viruses via wastewater. H5N1 is the first one we’re tracking via store-bought milk. (STAT

The first organ transplants from pigs to humans have not ended well, but scientists are learning valuable lessons about what they need to do better. (Nature

Another long read that’s worth your time: an inside look at just how long 3M knew about the pervasiveness of “forever chemicals.” (New Yorker

That viral video showing a head transplant is a fake. But it might be real someday. 

An animated video posted this week has a voice-over that sounds like a late-night TV ad, but the pitch is straight out of the far future. The arms of an octopus-like robotic surgeon swirl, swiftly removing the head of a dying man and placing it onto a young, healthy body. 

This is BrainBridge, the animated video claims—“the world’s first revolutionary concept for a head transplant machine, which uses state-of-the-art robotics and artificial intelligence to conduct complete head and face transplantation.”

First posted on Tuesday, the video has millions of views, more than 24,000 comments on Facebook, and a content warning on TikTok for its grisly depictions of severed heads. A slick BrainBridge website has several job postings, including one for a “neuroscience team leader” and another for a “government relations adviser.” It is all convincing enough for the New York Post to announce that BrainBridge is “a biomedical engineering startup” and that “the company” plans a surgery within eight years. 

We can report that BrainBridge is not a real company—it’s not incorporated anywhere. The video was made by Hashem Al-Ghaili, a Yemeni science communicator and film director who in 2022 made a viral video called “EctoLife,” about artificial wombs, that also left journalists scrambling to determine if it was real or not.

Yet BrainBridge is not merely a provocative work of art. This video is better understood as the first public billboard for a hugely controversial scheme to defeat death that’s recently been gaining attention among some life-extension proponents and entrepreneurs. 

“It’s about recruiting newcomers to join the project,” says Al-Ghaili.

This morning, Al-Ghaili, who lives in Dubai, was up at 5 a.m., tracking the video as its viewership ballooned around social media. “I am monitoring its progress,” he says, but he insists he didn’t make the film for clicks: “Being viral is not the goal. I can be viral anytime. It’s pushing boundaries and testing feasibility.”

The video project was bankrolled in part by Alex Zhavoronkov, the founder of Insilico Medicine, a large AI drug discovery company, who is also a prominent figure in anti-aging research. After Zhavoronkov posted the video on his LinkedIn account, commenters noticed that it is his face on the two bodies shown in the video.

“I can confirm I helped design and fund a few things,” Zhavoronkov told MIT Technology Review in a WhatsApp message, in which he also claimed that “some important and famous people are supporting [it] financially.”

Zhavoronkov declined to name these individuals. He also didn’t respond when asked if the job ads—whose cookie-cutter descriptions of qualifications and responsibilities appear to have been written by an AI—are real roles or make-believe positions.

Aging bypass

What is certain is that head transplantation—or body transplant, as some prefer to call it—is a subject of growing, if speculative, interest in longevity circles, the kind inhabited by biohackers, techno-anarchists, and others on the fringes of biotechnology and the startup scene and who form the most dedicated cadre of extreme life-extensionists.

Many proponents of longer life spans will admit things don’t look good. Anti-aging medicine so far hasn’t achieved any breakthroughs. In fact, as research advances into the molecular details, the problem of death only looks more and more complicated. As we age, our billions of cells gradually succumb to the irreversible effects of entropy. Fixing that may never be possible.

By comparison, putting your head on a young body looks comparatively easy—a way to bypass aging in a single stroke, at least as long as your brain holds out. The idea was strongly endorsed in a technical road map put forward this year by the Longevity Biotech Fellowship, a group espousing radical life extension, which rated “body replacement” as the cheapest, fastest pathway to “solve aging.”  

Will head transplants work? In a crude way, they already have. In the early 1970s, the American neurosurgeon Robert White performed a “cephalic exchange,” cutting off the head of a monkey, placing it on the body of another, and sewing together their circulatory systems. Reports suggest the head remained conscious, and able to see, for a few days before it died.

Most likely, a human head transplant would also be fatal. But even if you lived, you’d be a mind atop a paralyzed body, since exchanging heads means severing the spinal cord. 

Yet head-swapping proponents can point to plausible solutions for that, too—a number of which appear in the BrainBridge video. In Europe, for instance, some paralyzed people have walked again after doctors bridged their spinal injuries with electronics. Other scientists in China are studying growth factors to regrow nerves.

Joined at the neck

As shocking as the video is, BrainBridge is in some ways overly conventional in its thinking. If you want to keep your brain going, why must it be on a human body? You might instead keep the head alive on a heart-lung machine—with an Elon Musk neural implant to let it surf the internet, for as long as it lives. Or consider how doctors hoping to solve the organ shortage have started putting hearts and kidneys from genetically engineered pigs into patients. If you don’t mind having a tail and four legs, maybe your head could be placed onto a pig’s body.

Let’s take it a step further. Why does the body “donor” have to be dead at all? Anatomically, it’s possible to have two heads. There are conjoined twins who share one body. If your spouse were diagnosed with a fatal cancer, you would surely welcome his or her head next to yours, if it allowed their mind to live on. After all, the concept of a “living donor” is widely accepted in transplant medicine already, and married couples are often said to be joined at the hip. Why not at the neck, too?

If the video is an attempt to take the public’s temperature and gauge reactions, it’s been successful. Since it was posted, thousands of commenters have explored the moral dilemmas posed by the procedure. For instance, if someone is left brain dead—say, in a motorcycle accident—surgeons can use their heart, liver, and kidneys to save multiple other people. Would it be ethical to use a body to help only one person?

“The most common question is ‘Where do you get the bodies from?’” says Al-Ghaili. The BrainBridge website answers this question by stating it will source “ethically grown” unconscious bodies from EctoLife, the artificial womb company that is Al-Ghaili’s previous fiction. He also suggests that people undergoing euthanasia because of chronic pain, or even psychiatric problems, could provide an additional supply. 

For the most part, the public seems to hate the idea. On Facebook, a pastor, Matthew. W. Tucker, called the concept “disgusting, immoral, unnecessary, pagan, demonic and outright idiotic,” adding that “they have no idea what they are doing.” A poster from the Middle East apologized for the video, joking that its creator “is one of our psychiatric patients who escaped last night.” “We urge the public to go about [their] business as everything is under control,” this person said.

Al-Ghaili is monitoring the feedback with interest and some concern. “The negativity is huge, to be honest,” he says. “But behind that are the ones who are sending emails. These are people who want to invest, or who are expressing their personal health challenges. These are the ones who matter.”

He says if suitable job applicants appear, the backers of BrainBridge are prepared to fund a small technical feasibility study to see if their idea has legs.

A device that zaps the spinal cord gave paralyzed people better control of their hands

Fourteen years ago, a journalist named Melanie Reid attempted a jump on horseback and fell. The accident left her mostly paralyzed from the chest down. Eventually she regained control of her right hand, but her left remained “useless,” she told reporters at a press conference last week. 

Now, thanks to a new noninvasive device that delivers electrical stimulation to the spinal cord, she has regained some control of her left hand. She can use it to sweep her hair into a ponytail, scroll on a tablet, and even squeeze hard enough to release a seatbelt latch. These may seem like small wins, but they’re crucial, Reid says.

“Everyone thinks that [after] spinal injury, all you want to do is be able to walk again. But if you’re a tetraplegic or a quadriplegic, what matters most is working hands,” she said.

Reid received the device, called ARCex, as part of a 60-person clinical trial. She and the other participants completed two months of physical therapy, followed by two months of physical therapy combined with stimulation. The results, published today in Nature Medicine, show that the vast majority of participants benefited. By the end of the four-month trial, 72% experienced some improvement in both strength and function of their hands or arms when the stimulator was turned off. Ninety percent had improvement in at least one of those measures. And 87% reported an improvement in their quality of life.

This isn’t the first study to test whether noninvasive stimulation of the spine can help people who are paralyzed regain function in their upper body, but it’s important because a trial has never been done before in this number of rehabilitation centers or in this number of subjects, says Igor Lavrov, a neuroscientist at the Mayo Clinic in Minnesota, who was not involved in the study. He points out, however, that the therapy seems to work best in people who have some ability to move below the site of their injury. 

The trial was the last hurdle before the researchers behind the device could request regulatory approval, and they hope it might be approved in the US by the end of the year.

ARCex consists of a small stimulator connected by wires to electrodes placed on the spine—in this case, in the area responsible for hand and arm control, just below the neck. It was developed by Onward Medical, a company cofounded by Grégoire Courtine, a neuroscientist at the Swiss Federal Institute of Technology in Lausanne and now chief scientific officer at the company.

The stimulation won’t work in the small percentage of people who have no remaining connection between the brain and spine below their injury. But for people who still have a connection, the stimulation appears to make  voluntary movements easier by making the nerves more likely to transmit a signal. Studies over the past couple of decades in animals suggest that the stimulation activates remaining nerve fibers and, over time, helps new nerves grow. That’s why the benefits persist even when the stimulator is turned off.

The big advantage of an external stimulation system over an implant is that it doesn’t require surgery, which makes using the device less of a commitment. “There are many, many people who are not interested in invasive technologies,” said Edelle Field-Fote, director of research on spinal cord injury at the Shepherd Center, at the press conference. An external device is also likely to be cheaper than any surgical options, although the company hasn’t yet set a price on ARCex. 

“What we’re looking at here is a device that integrates really seamlessly with the physical therapy and occupational therapy that’s already offered in the clinic,” said Chet Moritz, an engineer and neuroscientist at the University of Washington in Seattle, at the press conference. The rehab that happens soon after the injury is crucial, because that’s when the opportunity for recovery is greatest. “Being able to bring that function back without requiring a surgery could be life-changing for the majority of people with spinal cord injury,” he adds.

Reid wishes she could have used the device soon after her injury, but she is astonished by the amount of function she was able to regain after all this time. “After 14 years, you think, well, I am where I am and nothing’s going change,” she says. So to suddenly find she had strength and power in her left hand—“It was extraordinary,” she says.

Onward is also developing implantable devices, which can deliver stronger, more targeted stimulation and thus could be effective even in people with complete paralysis. The company hopes to launch a trial of those next year.

The burgeoning field of brain mapping

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 human brain is an engineering marvel: 86 billion neurons form some 100 trillion connections to create a network so complex that it is, ironically, mind boggling.

This week scientists published the highest-resolution map yet of one small piece of the brain, a tissue sample one cubic millimeter in size. The resulting data set comprised 1,400 terabytes. (If they were to reconstruct the entire human brain, the data set would be a full zettabyte. That’s a billion terabytes. That’s roughly a year’s worth of all the digital content in the world.)

This map is just one of many that have been in the news in recent years. (I wrote about another brain map last year.) So this week I thought we could walk through some of the ways researchers make these maps and how they hope to use them.  

Scientists have been trying to map the brain for as long as they’ve been studying it. One of the most well-known brain maps came from German anatomist Korbinian Brodmann. In the early 1900s, he took sections of the brain that had been stained to highlight their structure and drew maps by hand, with 52 different areas divided according to how the neurons were organized. “He conjectured that they must do different things because the structure of their staining patterns are different,” says Michael Hawrylycz, a computational neuroscientist at the Allen Institute for Brain Science. Updated versions of his maps are still used today.

“With modern technology, we’ve been able to bring a lot more power to the construction,” he says. And over the past couple of decades we’ve seen an explosion of large, richly funded mapping efforts.

BigBrain, which was released in 2013, is a 3D rendering of the brain of a single donor, a 65-year-old woman. To create the atlas, researchers sliced the brain into more than 7,000 sections, took detailed images of each one, and stitched the sections into a three-dimensional reconstruction.

In the Human Connectome Project, researchers scanned 1,200 volunteers in MRI machines to map structural and functional connections in the brain. “They were able to map out what regions were activated in the brain at different times under different activities,” Hawrylycz says.

This kind of noninvasive imaging can provide valuable data, but “Its resolution is extremely coarse,” he adds. “Voxels [think: a 3D pixel] are of the size of a millimeter to three millimeters.”

And there are other projects too. The Synchrotron for Neuroscience—an Asia Pacific Strategic Enterprise,  a.k.a. “SYNAPSE,” aims to map the connections of an entire human brain at a very fine-grain resolution using synchrotron x-ray microscopy. The EBRAINS human brain atlas contains information on anatomy, connectivity, and function.

The work I wrote about last year is part of the $3 billion federally funded Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which launched in 2013. In this project, led by the Allen Institute for Brain Science, which has developed a number of brain atlases, researchers are working to develop a parts list detailing the vast array of cells in the human brain by sequencing single cells to look at gene expression. So far they’ve identified more than 3,000 types of brain cells, and they expect to find many more as they map more of the brain.

The draft map was based on brain tissue from just two donors. In the coming years, the team will add samples from hundreds more.

Mapping the cell types present in the brain seems like a straightforward task, but it’s not. The first stumbling block is deciding how to define a cell type. Seth Ament, a neuroscientist at the University of Maryland, likes to give his neuroscience graduate students a rundown of all the different ways brain cells can be defined: by their morphology, or by the way the cells fire, or by their activity during certain behaviors. But gene expression may be the Rosetta stone brain researchers have been looking for, he says: “If you look at cells from the perspective of just what genes are turned on in them, it corresponds almost one to one to all of those other kinds of properties of cells.” That’s the most remarkable discovery from all the cell atlases, he adds.

I have always assumed the point of all these atlases is to gain a better understanding of the brain. But Jeff Lichtman, a neuroscientist at Harvard University, doesn’t think “understanding” is the right word. He likens trying to understand the human brain to trying to understand New York City. It’s impossible. “There’s millions of things going on simultaneously, and everything is working, interacting, in different ways,” he says. “It’s too complicated.”

But as this latest paper shows, it is possible to describe the human brain in excruciating detail. “Having a satisfactory description means simply that if I look at a brain, I’m no longer surprised,” Lichtman says. That day is a long way off, though. The data Lichtman and his colleagues published this week was full of surprises—and many more are waiting to be uncovered.


Now read the rest of The Checkup

Another thing

The revolutionary AI tool AlphaFold, which predicts proteins’ structures on the basis of their genetic sequence, just got an upgrade, James O’Donnell reports. Now the tool can predict interactions between molecules. 

Read more from Tech Review’s archive

In 2013, Courtney Humphries reported on the development of BigBrain, a human brain atlas based on MRI images of more than 7,000 brain slices. 

And in 2017, we flagged the Human Cell Atlas project, which aims to categorize all the cells of the human body, as a breakthrough technology. That project is still underway

All these big, costly efforts to map the brain haven’t exactly led to a breakthrough in our understanding of its function, writes Emily Mullin in this story from 2021.  

From around the web

The Apple Watch’s atrial fibrillation (AFib) feature received FDA approval to track heart arrhythmias in clinical trials, making it the first digital health product to be qualified under the agency’s Medical Device Development Tools program. (Stat)

A CRISPR gene therapy improved vision in several people with an inherited form of blindness, according to an interim analysis of a small clinical trial to test the therapy. (CNN)

Long read: The covid vaccine, like all vaccines, can cause side effects. But many people who say they have been harmed by the vaccine feel that their injuries are being ignored.  (NYT)