CRISPR Can Speed Up Nature—and Change How We Grow Food

- July 17, 2018 

LIKE ANY SELF-RESPECTING farmer, Zachary Lippman was grumbling about the weather. Stout, with close-cropped hair and beard, Lippman was standing in a greenhouse in the middle of Long Island, surrounded by a profusion of rambunctiously bushy plants. “Don’t get me started,” he said, referring to the late and inclement spring. It was a Tuesday in mid-April, but a chance of snow had been in the forecast, and a chilly wind blew across the island. Not the sort of weather that conjures thoughts of summer tomatoes. But Lippman was thinking ahead to sometime around Memorial Day, when thousands of carefully nurtured tomato plants would make the move from the greenhouse to Long Island loam. He hoped the weather would finally turn.

ALTHOUGH HE WORKED on a farm as a teenager and has a romantic attachment to the soil, ­Lippman isn’t a farmer. He’s a plant biologist at Cold Spring Harbor Laboratory in New York with an expertise in genetics and development. And these greenhouse plants aren’t ordinary tomatoes.

After introducing me to his constant companion, Charlie (a slobberingly gregarious Labrador-Rottweiler mix), Lippman walked me through hundreds of plants, coddled by 80-degree daytime temperatures and 40 to 60 percent humidity, and goaded into 14 hours of daily photosynthetic labor by high-pressure sodium lights overhead. Some were seedlings that had barely unfurled their first embryonic leaves; others had just begun to flash their telltale yellow flowers, harbingers of the fruit to come; still others were just about ripe, beginning to sag with the weight of maturing red fruit.

What makes this greenhouse different—what makes it arguably an epicenter of a revolution in plant biology that may forever change not just the future of the tomato but the future of many crops—is that 90 percent of the tomato plants in the building had been genetically altered using the wizardly new gene-editing tool known as Crispr/Cas-9. ­Lippman and Joyce Van Eck, his longtime collaborator at the Boyce Thompson Institute in Ithaca, New York, are part of a small army of researchers using gene editing to turn the tomato into the laboratory mouse of plant science. In this greenhouse, Crispr is a verb, every plant is an experiment, and mutant isn’t a dirty word.

Lippman walked to the rear of the building and pointed out a variety of tomato known as Large Fruited Fresh Market—one of the commercial varieties that turn up in supermarkets, not farmer’s markets. This particular plant, about two months old, bowed with big, nearly ripe fruit. It was, Lippman explained, a mutant called “jointless.” Most tomato varieties have a swollen knuckle of tissue (or joint) on the stem, just above where the fruit forms; when the tomato is ready, it tells itself, as Lippman put it, “OK, I’m ripe—time to fall,” and the cells in the joint receive a signal to die, letting go of the tomato. That is nature’s way of spreading tomato seeds, but the joint has been a thorny problem for agricultural production, because it leaves a residual stem that pokes holes in mechanically harvested fruit. Jointless tomatoes, whose stems can be plucked clean, have been bred and grown commercially, but often with unwanted side effects; these gene-edited versions avoid the unintended consequences of traditional breeding. “We can now use Crispr to go in and directly target that gene for the molecular scissors to cut, which leads to a mutation,” ­Lippman said. “Voilà: the jointless trait in any variety you want.”

We moved on to several examples of Physalis pruinosa, a relative of the tomatillo that produces a small, succulent fruit called a ground cherry. The plant has never been domesticated, and Lippman referred to the wild version as a “monstrosity”: tall, unkempt, and stingy, bestowing a single measly fruit per shoot. Next to it stood a Physalis plant after scientists had induced a mutation called “self-­pruning.” It was half as tall, much less bushy, and boasted half a dozen fruits per shoot. Lippman plucked a ground cherry off one of the mutated plants and offered it to me.

“Smell it first,” he entreated. “Enjoy the smell.” It was exotic and faintly tropical. I popped it in my mouth and bit into a complex burst of flavor. Like all its cousin tomatoes, the taste was a mystical, time-lapse blur of sugar and acidity, embellished by the whiff of volatile compounds that found my nose and rounded out the flavor.

“You just ate an edited plant,” Lippman said with a smile. “But don’t be too nervous.”

Like the majority of scientists, Lippman regards genetically modified plants as safe to eat. But his mischievous smile acknowledged that not everyone views the technology as innocuous. There is a lot of nervousness about genetic tinkering with food plants. Genetically modified (GM) “transgenic” crops such as corn and soybeans have infiltrated processed foods, animal feed, and biofuels for many years, and the battle over them has long divided the public in the US and overseas. The Crispr revolution is reinventing, if not reigniting, that debate. Most of the plants that have been gene-edited to date have been created by knocking out genes (that is, mutating them), not by introducing genes from unrelated species, as first-generation genetic modification generally did—rousing cries of “Frankenfoods” and fears of environmental contamination. Precisely because it’s subtraction rather than addition, scientists argue that this form of gene editing mimics the process of agriculturally induced mutations that characterizes traditional plant breeding. This distinction may not assuage critics, but it has apparently persuaded federal regulators; gene-edited soybean and potato crops are already in the ground, and last March the US Department of Agriculture declared that crops developed with gene-edited mutations are “indistinguishable” from those produced by traditional breeding and “do not require regulatory oversight.”

Huge questions vex the future of food—how to feed 9 billion mouths, how to farm in an era of unprecedented climate uncertainty, how to create more resilient and nutritious foods for a public wary of the new technology. Plant scientists are already using Crispr and related technologies to reshape food crops in dramatic ways—editing wheat to reduce gluten, editing soybeans to produce a healthier oil, editing corn to produce higher yields, editing potatoes to store better (and not throw off a carcinogen when cooked). In both industrial and academic labs, new editing tools are being developed that will have a profound impact on the foods all of us eat. Yet this newfound power to transform food traits coincides with a moment when the agriculture business has consolidated into essentially three mega-conglomerates. Those companies have the money to put this new technology to use. The question is: What use will they put it toward?

Soybeans, potatoes, and corn melt invisibly into the food chain, but tomatoes add a big red exclamation point to the current debate. Perhaps no food crop is more emblematic of what is at stake—agriculturally, biologically, culturally, and perhaps even in homegrown foodie ways—than the tomato: queen of the farmer’s market, jewel of the backyard garden, alpha vegetable of locavores everywhere. Lippman’s greenhouse reveals just some of the ways gene editing is already altering the tomato—he has plants that flower earlier, that are oblivious to daylight cues, that prune themselves into smaller footprints, that can be genetically programmed to space out the position of fruits on the stem like an accordion.

For people who love to eat or grow tomatoes (I do both), the arrival of Crispr provokes both cynicism and giddy hope about the future of our favorite vegetable. Cynicism because most of the practical scientific efforts would perpetuate the dreary taste of commercially produced tomatoes. In one sense, this is simply the latest in a century-­long conquest of the produce aisles by the desires of food growers, who prize greater yield at lesser cost, over the desires of consumers, who cherish taste and nutrition. (Harry Klee, a tomato expert at the University of Florida, says that the perfect tomato for industry is one that exactly matches the size of a McDonald’s hamburger.) Hope because there is something intriguing about using new technology to preserve the ravishing, sweet acidic burst of an heirloom tomato in a hardier, disease-­resistant plant—an heirloom-plus, if you will.

After Lippman walked me through his garden of man-made mutations, I couldn’t resist asking if the heirlooms I struggle to grow every year might also benefit from Crispr’s scissors.

“We’re not doing any editing of heirlooms,” Lippman said. “Not yet. But it’s in the works. They could benefit from a little bit of tweaking.”

THIS IS A story about tomatoes, of course. But it is also, like all agricultural stories, about mutations—“natural” mutations and man-made mutations, invisibly insidious mutations and overtly grotesque mutations, mutations that were created earlier this year at Cold Spring Harbor Laboratory and mutations that may have occurred 10,000 years ago, like the ones that transformed Solanum pimpinellifolium from a scraggly perennial weed producing pea-sized fruit along the Pacific coastal margins of Peru and Ecuador to those beautiful big-lobed heirlooms in your backyard. Our cultural thesaurus has reduced the word mutant to a term of derision, but if you think mutation is a dirty word, you should probably stop reading—and probably stop eating plant-based food too. The foundational principle of plant breeding is to take advantage of genetic modification, whether the mutation is caused by sunlight or x-rays or Crispr. As Klee puts it, “there isn’t a single crop that I know of in your produce aisle that is not drastically modified from what is out there in the wild.”

Every backyard gardener is a connoisseur, witting or otherwise, of mutation. The intense, thin-skinned freshness of Brandywines, the apricot glow of Jaune Flamme, the green standoffish shoulders of Black Krims, and my personal favorite, Rose de Berne, with its blush of color and amazing taste—all those heirlooms are the product of long-ago, hand-me-down mutations.

Every spring, almost inevitably during March Madness (this year, during Villanova-Michigan), I get down on the floor with a bunch of peat pots and starter soil and clumsily press seeds of all of the above varieties into virgin dirt. My wife wonders why I can’t buy seedlings at the market like everyone else, but I’ve never outgrown the childlike thrill of watching an itty-bitty snippet of plant DNA, encased in the stiff callus of a seed coat, unfurl into a 5-foot-tall plant that yields its sublime bounty. Gardeners—the original DIY biologists—all know this thrill. And so does Lippman. That’s how he got into gene-editing tomatoes in the first place.

Lippman grew up in Milford, Connecticut; his father was an English teacher and his mother worked in health care. Among his earliest memories is visiting a nearby farm with his father when he was 6 or 7 years old and picking up leftover Halloween pumpkins and gourds—with their mind-blowing shapes and colors—that littered the field.

That pumpkin field was part of Robert Treat Farm, and when he was 13, Lippman began working summers there, cultivating his fascination with plants. By the time he graduated from high school in 1996, he had decided to pursue plant breeding and genetics, first at Cornell University and then at Cold Spring Harbor, where he got his PhD and is now a Howard Hughes Medical Institute investigator.

Lippman’s office is a shrine to the tomato: On his walls are old tomato-­can labels and antique postcards of implausibly gigantic tomatoes, and thousands of little brown envelopes containing seeds, each marked by year and variety, are stacked on his desk, in old seed boxes, in wooden trays and plastic cabinets against the wall. The most telling relic is just behind the door: a large framed reproduction from a 16th-century book by Pietro Andrea Mattioli, believed to be the earliest color depiction of the tomato following the Spanish conquest of the Americas. To a geneticist like Lipp­man, the Mattioli print is especially significant because it is early evidence that pre-Columbian cultures knew a beneficial tomato mutation when they saw one—they had already converted the nubbin of wild fruit into a large, multiple-lobed golden beefsteak.

Up until the 1930s, agricultural scientists essentially relied on the same techniques as the original tomato farmers in Central America: Be patient enough to wait for nature to produce a useful mutation, be smart enough to recognize that desirable trait (bigger fruit, for example), and be clever enough to create a new variety with that trait by selecting the mutant strains and propagating them. Put another way, agriculture has always been about unnaturalselection—human choice privileging certain mutations while discarding others. Biologists sped up this process around the time of World War II by deliberately inducing random mutations in seeds with the use of chemicals, x-rays, and other forms of radiation. But even so, the process was slow. Selective breeding of a desirable trait could easily take a decade.

This all began to change in 2012, an annus mirabilis for the tomato. In May of that year, plant geneticists completed the Tomato Genome Project—the entire DNA sequence of the tomato plant, all 900 million base pairs on 12 chromosomes. Then, in June, a group led by Jennifer Doudna at UC Berkeley published the first report on the new gene-editing technique known as Crispr, followed soon after by a group at the Broad Institute of MIT and Harvard. The fruit of those two converging streams of research—and, yes, botanically speaking, tomato is a fruit—was a race among scientists to see if the new technique worked in plants.

As soon as word of Crispr broke, Lippman wondered, “Can we do it in tomato? And if we can, let’s move.” Moving fast meant doing an experiment on a tomato gene that would prove the efficacy of Crispr without too much delay. Which gene did Lippman and Van Eck target? Not one that would improve the size or shape of the fruit—that would take too long, and Van Eck was impatient. “I don’t want to have to put it in the greenhouse and wait for it to grow,” she told Lippman. “I want to be able to see something in the petri plate.” So they picked a gene that was of zero economic significance and less-than-zero consumer appeal. It was a weird gene that, when mutated, produced disfigured tomato leaves that looked like needles. The mutant version was called “wiry.”

THE WIRY MUTATION was so obscure that Van Eck had to dig up a paper from 1928 that described it for the first time to know what she’d be looking for. Each Crispr-directed mutation requires a customized, genetically engineered tool called a “construct”—a so-called guide RNA to target the right tomato gene and an enzyme riding shotgun to cut the plant DNA at precisely that spot. In this case, Lippman designed the construct to target the wiry gene and cut it; the mutation is not created by Crispr per se but by the plant when it attempts to repair the wound. Van Eck used a bacterium that is very good at infecting plants to carry the Crispr mutation tool inside tomato cells. Once mutated, these cells were spread onto petri plates where they began to develop into plants. Van Eck still had to wait about two months before the tomato cells developed into seedlings and sprouted leaves, but it was worth the wait.

“I still remember when I saw the first leaves coming up,” she recalls. The leaves were “radialized”—curled up into needlelike shapes. “Omigod, it worked!” she cried, and raced down the hallways of the institute to tell anyone who would listen. “I was thrilled because, you know, when does something work the first time?”

Not only had they demonstrated that Crispr could produce a heritable trait change in a fruit crop, they also had their answer in two months rather than a year. They knew that the same basic process could theoretically be used to edit, with exquisite precision and unprecedented speed, any gene in any food crop.

As soon as they knew it worked, Lippman and Van Eck began Crispring every trait they’d wanted to study for the past 15 years. One of them was jointless. For 60 years, researchers had been trying to solve the problem of the joint on the tomato plant’s stem. Large-scale farming of tomatoes—California alone produces more than 10 million tons each year—requires mechanical harvesting, and those stabbing stems of jointed tomatoes make the task harder and more wasteful. Lippman, who studies plant architecture, knew that many jointless tomato plants produce excessive branching and lower yields. He discovered that this unintended consequence was the result of traditional breeding: When breeders favored the jointless mutation, they unwittingly produced unwanted branching as well because of a complex interaction between jointless and another ancient mutation. Traditional breeding produced another side effect—abnormally shaped tomatoes—because the process of selecting the jointless trait dragged along a chunk of DNA with an unwanted mutation. (This phenomenon is known as linkage drag.)

If Lippman could Crispr his way to the jointless mutation without dragging along the deleterious effects related to traditional breeding, it would offer a significant advance for growers. He and Van Eck had to wait longer than they had for the needle-nosed leaves of wiry, but by March 2016, Lippman had jointless tomatoes growing in his greenhouse. They published the work in the journal Cell in the spring of 2017, and Lippman shared the gene-editing tool with Klee at the University of Florida. Last March, Klee and his team planted a plot of gene-edited jointless mutants, in a commercial variety called Florida 8059, in a test field north of Gainesville.

QUICK REALITY CHECK: Despite the hype about the gene-editing revolution, the past couple of years have revealed limitations as well as successes. Scientists will tell you Crispr is great at “knocking out” a gene. But using it to insert a new gene and, as many popular accounts suggest, “rewrite” the germline of man, beast, or plant? Not so easy. “Crispr is not the be-all and end-all,” says Dan Voytas of the University of Minnesota, one of the pioneers of agricultural gene editing. Moreover, genomes are complex, even in plants. Just as a dozen knobs on a stereo console can shape the overall sound of a single song, multiple genetic elements can control the effect of a single gene.

That daunting complexity inspired Lippman’s lab to pursue a clever riff on gene editing. “I remember having a sticky note here,” Lippman says, pointing to his keyboard. The note simply read: “Promoter CRISPR.”

In plants as well as animals (and humans), there is part of the DNA that lies outside the protein-encoding segment of the gene and essentially regulates its output. This upstream patch of regulatory DNA is called the promoter, and it sets different levels of output—volume, if you will—for specific genes, from a little to a lot. What if, Lippman’s group asked, you could use Crispr to, in effect, adjust the volume of a particular gene, turning it up or down like a stereo knob, by mutating the promoter in different places?

The Long Island greenhouse is now full of examples of what happens. As they reported in Cell last October, Daniel Rodríguez-­Leal and colleagues in Lippman’s lab showed that, by mutating the promoter of the self-pruning gene in different places, they could adjust its output like a dimmer switch, producing subtle but important changes. By using Crispr to create varying doses of a gene, Lippman says, scientists can now find “better” versions of plants than nature ever provided.

But better for whom? One of Lippman’s pet phrases is “sweet spot”—that point of genetic balance where desirable traits for agriculture can be improved without sacrificing essential features like flavor or shape. “Now we can start to think about taking some of our best tomato varieties, and if they can flower faster, you can start to grow them in more northern latitudes, where the summers are shorter,” he says. “We can begin to imagine new crops, or new versions of existing crops, for urban agriculture, like tiered cropping that they have in these abandoned warehouses ... Adapt the plant so that it’s more compact, flowers faster, gives you a nice-sized fruit with a decent yield, in a very compressed growth setting, with the equivalent of protective agriculture—greenhouse conditions—but with LED lights.” Because every plant gene comes with its own promoter, this genetic “tuning,” as Lippman puts it, could apply to virtually any vegetable crop.

Tuning is just one of many ways biologists are remaking the tomato. Last year, researchers at the Sainsbury Laboratory in England gene-edited a tomato variety called Moneymaker to be resistant to powdery mildew, and a Japanese research group recently created tomatoes without seeds. On the day in May that I set my first heirloom seedlings into the ground, I happened to have a Skype conversation with two plant biologists in Brazil who have taken the gene editing of tomatoes to a whole new level. In collaboration with the Voytas lab at the University of Minnesota, Agustin Zsögön of the University of Viçosa and Lázaro Peres of the University of São Paulo claim to have, in essence, reverse-­engineered the weedlike wild tomato believed to be the fore­runner of all cultivated varieties. (They haven’t published this work to date, but have discussed it at meetings.) Rather than tweak a domesticated variety of tomato, they went back to square one—the wild plant—and used Crispr to knock out a handful of genes all at once. The result? Where the wild plant was sprawling and weedy, the gene-edited tomato was compact and bushy; where the ancestral plant had pea-sized fruit, the gene-­edited version had reasonably plump, cherry-sized tomatoes. The edited fruit also contained more lycopene, an important antioxidant, than any other known variety of tomato. The process is called “de novo domestication.”

“We didn’t go from pea-sized to beefsteak, but we went from pea-sized to cherry-sized,” said Zsögön of this first attempt. And how did the tomatoes taste? “They taste great!” Peres insisted. In a similar vein, Lippman and Van Eck are domesticating the wild ground cherry in the hope that it can join blueberries and strawberries as one of the basic berry crops.

What makes the de novo approach so intriguing is that it takes advantage of all the accumulated botanical “wisdom” of a wild plant. Over tens of thousands of years of evolution, a wild species acquires traits of hardiness and resilience, such as resistance to disease and stress. Domestication eliminated some of those traits. Since those resistance traits typically involve a suite of genes, Peres says, they would be extremely difficult to introduce into domesticated tomatoes, via Crispr or any other technology. And the approach can exploit other extreme traits. Peres wants to “domesticate” a wild species from the Galapagos, which can tolerate extreme environmental conditions such as high salinity and drought—traits that might enhance food security in a future with enormous climate fluctuations.

Rising temperatures. Changing growing seasons. A rising global population. The environmental toll of herbicide overuse. What if gene editing, for example, could favor disease-­resistance genes that would reduce pesticide use?  Lippman asks. “That’s not just feeding the world, that’s protecting the planet.”

ALL THIS NEW plant science—knocking out genes, fiddling with the volume knob of promoters, de novo domestication—is wonderfully creative and happening very fast. But sooner or later, the other shoe drops in the conversation. Will consumers want to eat these tomatoes? Are Crispr vegetables and grains simply “new GMOs,” as a number of environmental groups maintain, or are gene-edited plants intrinsically different? “This is the beginning of the new conversation,” Lippman says.

The old conversation was acrimonious and emotional. The initial GM foods that Monsanto introduced in the 1990s were “transgenic,” meaning that biologists used genetic engineering to introduce foreign DNA, from an unrelated species, into the plant. Gene editing is much more analogous to older forms of mutagenesis such as irradiation and chemicals, though much less scattershot. Rather than creating random mutations, Crispr targets specific genes. (Editing that misses its mark is possible, though Lippman hasn’t detected any in his work.) That is why plant scientists have been so eager to use it, and why the USDA regards gene-­edited knockouts as similar to earlier mutagens and thus not requiring special regulation. (In the case of “knocking in,” or adding, a gene to crop plants, the USDA has indicated it will assess on a case-by-case basis.) Some European countries have banned GMOs, and the European Union has yet to issue a final judgment on gene-edited plants.

Although multiple studies have failed to show that GMOs pose a threat to human health, public doubts persist—a Pew Research Center survey in 2016 indicated that 39 percent of Americans believe that genetically modified foods are less healthy than non-GMOs, and in his household, Lippman admits, his wife initially preferred not to eat his gene-edited tomatoes.

There are other reasons that genetically altered foods continue to arouse suspicion. Monsanto’s early GMO effort used a revolutionary technology not to make healthier or more environmentally sustainable foods but to confer resistance in soybean and corn to the company’s proprietary herbicide, Roundup. The company’s aggressive promotion of such a self-­serving first product was considered a public relations disaster.

Big agribusinesses are now positioning themselves to take advantage of gene editing. A recent rash of mergers has created three giant multinationals in global agriculture: Bayer (which completed its acquisition of Monsanto this year), DowDuPont (following Dupont’s earlier merger with Dow Chemical), and Syngenta (which was acquired last year by the huge Chinese gene-­editing company ChemChina). The intellectual property issues are possibly more complex than plant genetics. Both the Broad Institute and DuPont Pioneer hold basic Crispr patents that apply to agriculture, and the two entities teamed up last fall to jointly negotiate licenses for farming applications (all three giant agribusinesses have licensed the technology). According to agricultural sources, the right to use Crispr for commercial agriculture requires an upfront fee, annual royalty payments on sales, and other conditions. (The Broad Institute did not discuss licensing terms, except to say that it is not involved in product development.)

This is where gene editing bumps up against the harsh economics of agriculture. Academic scientists can conduct basic research with Crispr without paying a licensing fee. But that’s as far as it goes. “I can’t develop products and start to sell them,” Lippman says. Commercial development requires payment of a licensing fee—a cost more easily borne by deep-pocketed agricultural companies.

There are some smaller biotechs seeking to maneuver around the giant companies and the intellectual property obstacles. Calyxt, a Minnesota-­based firm cofounded by Voytas, has already received USDA approval to grow several crops using an earlier and more-difficult-to-use gene-editing technology known as TALENs. Lippman consults for a Massachusetts startup called Inari. Benson Hill Biosystems, based in St. Louis, has been working on improving plant productivity using a patented set of new gene-editing scissors the company calls Crispr 3.0. But CEO Matthew Crisp (yes, that’s his name) claims innovation is being stifled by an intellectual property landscape that is “very murky.” Benson Hill’s partners and prospective licensees, he says, have complained that commercial rights to Crispr gene-editing technology are “too expensive, too cumbersome, or too uncertain.” The discovery of new gene-editing enzymes and other innovations may complicate the patent landscape even more. As one source put it, “It’s a mess. And it’s only going to get worse.”

That’s why there’s a lot of attention focused on a new startup called Pairwise Plants, in which Monsanto has teamed up with several Crispr pioneers from the Broad Institute. Recent statements to Bloomberg by company CEO Tom Adams, a former vice president of Monsanto, stressing new crops that are “really beneficial to people,” raised some eyebrows. “You know, it’s not Monsanto language,” Voytas noted. And the Monsanto pedigree has some plant biologists concerned. “The question will be: They have enormous baggage in terms of consumer acceptance,” Lippman says. “And if they botch it, they’re going to ruin it for everybody else. Everyone is sort of holding their breath.”

HERE’S A SIMPLER question: What about flavor? When I asked Harry Klee if he had tasted any of the jointless 8059 tomatoes he’s growing, he laughed and said he hadn’t bothered. “We know that Florida 8059 by itself doesn’t really have too much taste to begin with.” A better-tasting tomato always plays second fiddle to market economics. The majority of tomatoes grown in Florida, for example, go to the food service industry—“to the McDonald’s and Subways,” Klee says. “The sad reality,” Klee says, “is that industry is not really committed to making a better-tasting tomato.” Klee loves to talk about taste—he heads a group that identified about two dozen genetic regions related to exceptional tomato flavor. “We know exactly how to give you a sweeter tomato that will taste better,” he says. But those tomatoes are not as economically attractive to producers. “The growers won’t accept it.”

What about consumers? Would they accept a gene-­edited tomato if it tasted better? Or, to put it in a slightly more idiosyncratic way, would it be botanical blasphemy to gene-edit an heirloom?

In his tour of the greenhouse, Lippman paused at one point to express good-natured scorn for heirlooms. They are terrific tomatoes, he admits, but “pretty crappy producers.” From personal experience, I can confirm that heirlooms are finicky plants and stingy producers, with lousy immune systems—most of all, they’re heartbreakers, at least in the backyard. They start out like Usain Bolt in the 100 meters and end up looking spent, shriveled, hobbled by all manner of wilts and fungi and pests, leaves drooping like brown funereal crepe. It was tempting to think of using the new genetic tools to improve them. Klee is “very anxious to introduce gene editing into the home garden.” He thinks gardeners like me might be the place to make the argument that gene-edited tomatoes are not GMOs.

“What if I could give you a Brandywine that had high lycopene, longer shelf life, and was a more compact plant?” Klee asked me. “I could do all of those today, with knocking out genes and genome editing. And I could give you something that was virtually identical to Brandywine that was half as tall and had fruit that didn’t soften in less than a day, and were deep, deep red with high lycopene. I mean, would you grow that?”

“Absolutely!” I told him.

“I think most people would grow that,” he replied. “I think this could be a huge opportunity to educate home gardeners in what plant breeding is all about.”

Not everyone would agree with Klee (or me). Voytas, a pioneer of gene editing in plants, chuckled when I asked him about a gene-edited heirloom. “You know, part of it is, they’re heirloom,” he said. “The name inherently suggests this is something of value from the past. Not something new and techy.” More to the point, he reminded me of the “sort of outrageous” licensing fees for the gene-editing technology. “So your heirloom tomato idea would never be financially lucrative enough to pay the requisite licensing fees.”

The bottom line: Gene-edited tomatoes are probably on their way to the market. But tomatoes with better flavor? Probably not going to happen anytime soon.

IN EARLY JUNE, Zach Lippman went back to being a farmer. On what initially seemed like a sunny day, he and a dozen coworkers got their hands dirty transplanting some 8,000 gene-edited tomato plants into an outdoor field on the grounds of Cold Spring Harbor Laboratory. There were lots of the familiar mutants—jointless, self-pruning, daylight insensitivity. (The outdoor planting required prior approval from the USDA.) “Plant ’em deep!” he cried, as the crew raced to get the tomato seedlings in the ground under suddenly darkening skies.

The ultimate fate of the gene-edited tomato is as unpredictable as the weather, but the fate of these particular tomatoes is less of a mystery. Lippman often takes them home. “I’ve eaten many gene-edited tomatoes, yeah,” he laughs. (Not surprisingly, he finds “absolutely nothing” different about them.) “They’re not GMO,” he insists. “It’s just that you’re left with what would be equivalent to a natural mutation. So why not eat it? It’s one of just thousands or millions of mutations that may or may not affect the health of the plant … and we’re still eating them!”



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