by Antonio Regalado
A new wave of gene-edited crops are dodging regulators, and they’re about to reach stores.
When I visited Jason McHenry’s farm in South Dakota, the young farmer, dressed in worn jeans and sunglasses, led me up a slippery steel ladder on the side of a grain bin. We tumbled through the manhole into a shifting mountain of soybeans. You could sift them through your fingers and taste their sweet, cloudy flavor.
The U.S. soybean crop is four billion bushels a year, about 240 billion pounds. It generates the most cash receipts for American farms after cattle and corn. Of those beans, more than 90 percent are genetically modified organisms, or GMOs-that is, they’ve been genetically enhanced, most often through the addition of a gene from a soil bacterium that renders them immune to the weed killer glyphosate, commonly known as Roundup.
The 4,000 bushels McHenry and I were sitting in, however, represent a new type of plant that’s been modified using gene editing. A startup had employed the technology to introduce changes in two genes involved in fatty-acid synthesis, so that oil pressed from the beans is more like olive oil than typical soy oil.
McHenry first heard the pitch for the beans last December, at a hotel near the cooperative of South Dakota soybean processors. “We have something new and exciting,” a salesman told the farmers. “You’ve heard about the ban on trans fats?” Soybean oil has been losing market share since the U.S. government banned unhealthy fats created when soy oil is partially hydrogenated and turns to a solid (think Crisco). Those fats have been killing people. They’re bad food.
Oil from the gene-edited beans could solve that problem, because it doesn’t need to be processed in the same way. Any farmer who agreed to plant the beans, McHenry heard, would be part of the wave of innovation filling store shelves with Greek yogurts, green packaging, and healthy ingredients. What’s more, it would mean a few quarters more per bushel. “You make a little more money, you have a great experience, and you are part of a revolution,” said the pitchman, Thomas Stoddard, a lanky biologist turned seed seller who visited McHenry’s farm with me.
To McHenry, a farmer just starting out with his own acres, his own debts, and his own decisions, the pitch made sense. The Roundup-resisting beans his father still plants are expensive. What’s more, the tumbleweeds have evolved to survive spraying and grow as high as your waist. “Looking at the market as a whole, Europe and China are questioning GMOs,” McHenry says. “You have to keep your finger on what the consumer wants, and as a farmer, you have to differentiate yourself. If you are looking at a market that could be gone, you have to think about alternatives.”
The new beans are the creation of a startup called Calyxt, located 300 miles away, near Minneapolis, where Stoddard works, and nearly a straight shot east on Highway 90 from McHenry’s farm. At the company’s greenhouses, thousands of plants are being altered with gene editing every week. The virtue of the technology is that it lets scientists create designer plants that don’t have foreign DNA in them. The technique, which adds or deletes snippets of genetic information, is similar to what could be achieved through conventional breeding, only much faster. In essence, if there’s some quality about a soybean that you like, and if you know the genetic instructions responsible, gene editing can move them to another bean in a single molecular step.
To many scientists, the potential of gene editing seems nearly limitless, offering a new way to rapidly create plants that are drought-resistant, immune to disease, or improved in flavor. A supermarket tomato that tastes good? That could happen if scientists restore the flavor-making genes that make heirloom varieties delicious. What about a corn plant with twice as many kernels? If nature allows it, scientists believe, gene editing could let them build it.
There is another reason gene editing is causing excitement in industry. The U.S. Department of Agriculture has concluded that the new plants are not “regulated articles.” The reason is a legal loophole: its regulations apply only to GMOs constructed using plant pathogens like bacteria, or their DNA. That means Calyxt can commercialize its beans without going through the process of permits, inspections, and safety tests required for other genetically modified crops. It’s counting on that to cut at least half the 13 years and $130 million that companies have, on average, invested in order to create a new GMO and get it into farmers’ hands.
To GMO opponents, the new, unregulated plants are a source of alarm. For years, they have argued that GMOs should be opposed because they might be unsafe. What if they cause allergies or poison butterflies? Now the battle lines are shifting because companies like Calyxt can create plants without DNA from a different species in them. They can argue that gene editing is merely “accelerated breeding technology.”
To the critics, any attempt to reclassify engineered plants as natural is a dangerous fiction. “If they don’t have to go through the regulatory requirements, then it is game on again for genetic modification in agriculture,” says Jim Thomas, head of a nonprofit called the ETC Group that lobbies on environmental issues. “That is the prize. They are constructing a definition of a GMO so that gene editing falls outside it.”
Comment: Just one example of the push to ‘construct’ a new definition of GMO’s excluding gene editing technology: Gene editing: European Union folds under US pressure to exempt ‘New GMOs’
‘Gene editing is genetic engineering!’
The Commission’s decision transparently violates the EU’s own laws on GM crops and foods that require case-by-case risk assessment, detectability and labelling. GMOs are defined as any organism, with the exception of humans, “in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating or natural recombination”. Gene-edited plants and animals should therefore be covered by the law.
But in the US, GMOs are not systematically tested and can even be placed on the market without any form of testing. Labelling is not required although it soon will be in the state of Vermont. Gene-edited plants and animals are mostly unregulated. For example, US regulators ruled that Cibus’ SU Canola is exempt from regulation.
Already, the effort to persuade governments and food groups is reaching a planetary scale. New Zealand decided that the new plants are GMOs after all, and so did the USDA’s own organic council. The Netherlands and Sweden don’t think they are. China hasn’t said. The European Union still has to make up its mind. Billions in global grain exports could ultimately hang in the balance.
Opponents say they’re ready to fight for rules, regulations, and labels. “Our position has never changed. This is just a form of genetic engineering, so the same things should happen-there should be required safety assessments,” says Michael Hansen, a staff scientist at the Consumers Union, a lobby group attached to Consumer Reports magazine. “I can’t see this being resolved anytime soon.”
But McHenry has already accepted the argument. Pointing to his rows of grain bins, he ticked off whether the beans inside were GMOs or not. The one full of Calyxt beans he called “non-GMO.” “To me a GMO is [adding] an outside organism into a plant. The way I understand it there’s no foreign DNA put into the seed,” said McHenry. “It’s like we found a switch to make people’s lives easier. If it’s that easy, it makes sense to me.”
Drug companies see gene-editing technology as a versatile molecular scissors that could offer a radical new means to cure genetic diseases such as muscular dystrophy (see “Can CRISPR Save Ben Dupree?“). What’s not so widely appreciated is how close the technology is to large-scale implementation in agriculture and in our food. By the end of 2018, Calyxt says, it will be crushing beans and selling oil, potentially becoming the first company to enter the market with a gene-edited crop. At least one other crop is nearing commercialization from DuPont, which used gene editing to create a starchier corn plant.
To be sure, neither product is expected to take over farmland the way herbicide-resisting GMOs did. Instead, these initial examples are niche products with prosaic objectives. DuPont’s “waxy” corn is going to end up in glue sticks and as an emulsifier in salad dressing. Calyxt’s oil will fry doughnuts and chips. Even so, the mountain of beans at McHenry’s farm shows how quickly these crops could arrive. McHenry, making some fast calculations, estimated that we were sitting on 600 million of them. By then Stoddard, the salesman, had climbed into the story-tall grain bin too. “Gene editing is the future, and the first place it’s growing at scale is here in South Dakota,” he said reverently, letting beans drift through his hands.
Flipping a switch
The beans at McHenry’s farm are all descendants of a single soybean cell modified in 2012 by Dan Voytas, the cofounder of Calyxt and a professor of genetics at the University of Minnesota. Voytas told me he inherited a scientific interest in plants from his father, a government forest manager. “It was ‘Okay, son, what tree is that? Latin name, please,” he recalls.
I met Voytas at the startup’s greenhouse outside of Minneapolis, where he showed me fluid-mixing robots and a tall gene gun that fires the DNA into a plant cell. Green blobs growing on clear jelly in petri dishes were canola plants “regenerating” from a single cell after receiving new genetic instructions. The company has a staff of 35, two-thirds of whom are scientists. “We have a long list of ideas,” says Voytas. “But you can get a great oil and a sick plant. A lot of it is experimental.”
The startup uses a gene-editing technology called TALEN that Voytas helped develop-and patented. By the late 1990s, he had been part of a small group of biologists trying to move past the first round of GM plants not by adding entire genes, but instead by using cutting enzymes, called nucleases, to precisely sever the DNA chain-the life instructions found inside every living cell. To make Calyxt’s beans, Voytas used his technology to disable two genes.
Today, a different gene-editing technology, CRISPR, dominates the headlines, because it is easy to employ and inexpensive. However, because TALEN was developed two years earlier than CRISPR, the technique has advanced further toward commercial crops. Moreover, other plant biotech companies have been slowed by an ongoing patent fight over CRISPR, which left it unclear which of them would be able to use that technique.
In the meantime, Calyxt says, it has already used TALEN to design 19 plants and is banking on gene editing to make it one of the first small companies to introduce a successful genetically engineered crop. It says the USDA has already confirmed that six of its plants won’t be regulated, including, in September, an alfalfa plant modified to have less lignin, making it easier for cows and horses to digest. The company, which went public in July, has spent only $47 million so far.
Until now, every successful GMO on the market has had as its objective increasing the yield from each acre of farmland. Marketing “healthier” food made from GMOs has been a taller order. But if gene-edited plants can avoid the stigma of GMOs, that could change. In Calyxt’s view, that would open up valuable new uses of genetic engineering. In addition to its soybean oil, Calyxt claims it has changed wheat plants so they can be ground into white flour with three times as much fiber as usual. A bread company might even be able to claim that hamburger rolls help prevent cancer.
Some of the more radical changes gene editing may bring were apparent the day I visited Voytas at his university laboratory. He was meeting with his students, who diagrammed their plans on a whiteboard. (By now, all the students are using CRISPR.) A woman from Ethiopia wanted to change a local grain plant, teff, so that it stands up straight instead of drooping and losing seeds. Another student was investigating how to inject DNA into the stem cells found in the roots and shoots of growing plants. “We’re almost getting to the point where if you ask ‘What’s the best oil crop?’ we could create the genome to make that plant,” Voytas says.
Some significant obstacles remain. Drug companies working on gene therapy have learned it is easier to design and make DNA strands than to get them inside a person’s cells. That is also true of many plants, where delivery of the gene-editing ingredients is still difficult. Understanding which genes should be edited is yet another roadblock. Scientists know a lot about how oils are synthesized and why fruit turns brown. But the list of valuable plant traits whose genetic causes are both well understood and easy to alter drops off quickly after that. “Right now it’s a grab bag of traits,” says Rebecca Bart, a plant scientist at the Danforth Center, in St. Louis. “We still need to have pretty significant investment in discovery before you can manipulate them with gene editing. It has to go in that order.”
What’s more, for traits that are well understood, gene editing isn’t the only way to create such plants-just the newest. For instance, Calyxt’s soybeans will face competition from beans with similar oil content that are already on the market, including one, called Vistive Gold and sold by Monsanto, that was created via old-fashioned GMO technology. Voytas acknowledges that his beans aren’t entirely novel but says they will be a useful test of Calyxt’s fast-to-market business model and a way to prove to investors that the company can make money. “Calyxt is the first plant gene-editing company out there and needs to show it can commercialize products,” he says. “The advantage is getting to revenue in the short term.”
Some entrepreneurs think gene editing will have a big impact only when it can change the amount of food an acre can produce. “In real estate, the saying is ‘Location, location, location.’ Well, in agriculture, it’s ‘Yield, yield, yield,'” says Oliver Peoples, CEO of Yield10, a plant-engineering company in Cambridge, Massachusetts.
So Calyxt is also working on plants that could increase the amount of food farmers can reap, like a wheat plant resistant to powdery mildew. To date, no GMO wheat has ever been commercialized, partly because, as happens with many plants, wheat’s genome accumulates extra DNA like a closet that never gets cleared out. In fact, wheat is hexaploid-its cells harbor six mostly identical copies of every chromosome. That has made it massively complicated to genetically engineer, but Voytas says that with gene editing it is fairly easy. In a single reaction, the TALEN tools can search out and cut all six copies of any wheat gene they want to remove.
GMO or not?
Outside of Penn Station, in Manhattan, a 10-story-tall advertisement for Ketel One, a brand of vodka, declares that it is “made with 100% NON GMO grain.” At any supermarket, it is easy to find a profusion of similar claims, even for products like salt, which don’t contain plant material. About 40 percent of U.S. adults think foods made from GMOs are less healthy to eat.
Such beliefs are the result of warring messages from scientists, agriculture lobbies, and nonprofits like Greenpeace that stir doubts about the safety of GM organisms. The result for the first generation of GMOs has been a global split decision. While GMOs cover millions of acres of cropland in the U.S., Brazil, Argentina, and India, governments have banned the cultivation of such plants through much of the rest of the world, including France, Germany, China, and Russia.
Now the question is whether gene-edited crops can dodge the GMO label. Broadly speaking, companies argue that these plants should be unregulated because they could have been created by conventional breeding. The proof? In many cases, there would be no way to tell a gene-edited plant from a natural one.
GMO critics now fear a tidal wave of “frankenfood” if such plants slip through regulations, something that is already occurring in the U.S. The reason gene-edited plants can be exempt from USDA rules is that the agency employs an outdated 30-year-old definition of a GMO that is triggered only if a plant was modified using plant bacteria, as early products were. The agency, in January 2017, acknowledged that plants with even profound genetic alterations “may entirely escape regulation” depending on how they are made. Since then, four more gene-edited plants have been waved forward, including a salt- and drought-tolerant soybean developed by the USDA itself, Calyxt’s alfalfa plant, a type of camelina grass created by Yield10, and a species of millet with a delayed flowering time. “They’re trying to fit a square peg in a round hole of old laws not meant to address these new technologies,” says Gregory Jaffe, who follows biotechnology at the Center for Science in the Public Interest, in Washington, D.C.
What’s missing, then, is enough scrutiny of whether the plants could harm insects, spread their genetic enhancements to wild cousins, or create superweeds like the ones resistant to Roundup. Companies do typically consult with the U.S. Food and Drug Administration to confirm that their plants are safe to eat. But that process is voluntary. Jaydee Hanson, senior policy analyst at the Center for Food Safety, which promotes organic farming, thinks companies have been astute in starting with simple, even obscure, products. “The public has not had a chance to say ‘Wait a second,'” he says. “As we move into more complicated gene editing, there are going to be more questions. And we could see the same kind of kickback we saw before.”
The “GMO or not” question is going to be a global one. Food regulators will have to decide if store packaging needs to disclose the presence of gene-edited plants. Some organic associations have already said such plants cannot carry that label, reasoning that they really are GMOs. The European Court of Justice, meanwhile, is set to weigh in on the issue in Europe, where scientists have argued that gene editing is simply an advanced form of breeding. Opponents are counting on Europe to classify the plants as GMOs, a decision that would frustrate the technology’s spread.
“It would be sad if opponents won,” Voytas told me. We were in his office and students were passing outside his window, waiting to for a chance to review their gene-editing plans with him. Even undergraduates, he noted, are now able to edit plants. “In some sense,” he said, “I think the genie is out of the bottle.”
About the author
Antonio Regalado: I am the senior editor for biomedicine for MIT Technology Review. I look for stories about how technology is changing medicine and biomedical research. Before joining MIT Technology Review in July 2011, I lived in São Paulo, Brazil, where I wrote about science, technology, and politics in Latin America for Science and other publications. From 2000 to 2009, I was the science reporter at the Wall Street Journal and later a foreign correspondent.