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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. 

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.

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 76–page 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.”