What’s the Right Way to Regulate Gene-Edited Crops?
In the next few decades, humanity faces its biggest food crisis since the invention of the plow. The planet's population, currently 7.6 billion, is expected to reach 10 billion by 2050; to avoid mass famine, according to the World Resource Institute, we'll need to produce 70 percent more calories than we do today.
Imagine that a cheap, easy-to-use, and rapidly deployable technology could make crops more fertile and strengthen their resistance to threats.
Meanwhile, climate change will bring intensifying assaults by heat, drought, storms, pests, and weeds, depressing farm yields around the globe. Epidemics of plant disease—already laying waste to wheat, citrus, bananas, coffee, and cacao in many regions—will spread ever further through the vectors of modern trade and transportation.
So here's a thought experiment: Imagine that a cheap, easy-to-use, and rapidly deployable technology could make crops more fertile and strengthen their resistance to these looming threats. Imagine that it could also render them more nutritious and tastier, with longer shelf lives and less vulnerability to damage in shipping—adding enhancements to human health and enjoyment, as well as reduced food waste, to the possible benefits.
Finally, imagine that crops bred with the aid of this tool might carry dangers. Some could contain unsuspected allergens or toxins. Others might disrupt ecosystems, affecting the behavior or very survival of other species, or infecting wild relatives with their altered DNA.
Now ask yourself: If such a technology existed, should policymakers encourage its adoption, or ban it due to the risks? And if you chose the former alternative, how should crops developed by this method be regulated?
In fact, this technology does exist, though its use remains mostly experimental. It's called gene editing, and in the past five years it has emerged as a potentially revolutionary force in many areas—among them, treating cancer and genetic disorders; growing transplantable human organs in pigs; controlling malaria-spreading mosquitoes; and, yes, transforming agriculture. Several versions are currently available, the newest and nimblest of which goes by the acronym CRISPR.
Gene editing is far simpler and more efficient than older methods used to produce genetically modified organisms (GMOs). Unlike those methods, moreover, it can be used in ways that leave no foreign genes in the target organism—an advantage that proponents argue should comfort anyone leery of consuming so-called "Frankenfoods." But debate persists over what precautions must be taken before these crops come to market.
Recently, two of the world's most powerful regulatory bodies offered very different answers to that question. The United States Department of Agriculture (USDA) declared in March 2018 that it "does not currently regulate, or have any plans to regulate" plants that are developed through most existing methods of gene editing. The Court of Justice of the European Union (ECJ), by contrast, ruled in July that such crops should be governed by the same stringent regulations as conventional GMOs.
Some experts suggest that the broadly permissive American approach and the broadly restrictive EU policy are equally flawed.
Each announcement drew protests, for opposite reasons. Anti-GMO activists assailed the USDA's statement, arguing that all gene-edited crops should be tested and approved before marketing. "You don't know what those mutations or rearrangements might do in a plant," warned Michael Hansen, a senior scientist with the advocacy group Consumers Union. Biotech boosters griped that the ECJ's decision would stifle innovation and investment. "By any sensible standard, this judgment is illogical and absurd," wrote the British newspaper The Observer.
Yet some experts suggest that the broadly permissive American approach and the broadly restrictive EU policy are equally flawed. "What's behind these regulatory decisions is not science," says Jennifer Kuzma, co-director of the Genetic Engineering and Society Center at North Carolina State University, a former advisor to the World Economic Forum, who has researched and written extensively on governance issues in biotechnology. "It's politics, economics, and culture."
The U.S. Welcomes Gene-Edited Food
Humans have been modifying the genomes of plants and animals for 10,000 years, using selective breeding—a hit-or-miss method that can take decades or more to deliver rewards. In the mid-20th century, we learned to speed up the process by exposing organisms to radiation or mutagenic chemicals. But it wasn't until the 1980s that scientists began modifying plants by altering specific stretches of their DNA.
Today, about 90 percent of the corn, cotton and soybeans planted in the U.S. are GMOs; such crops cover nearly 4 million square miles (10 million square kilometers) of land in 29 countries. Most of these plants are transgenic, meaning they contain genes from an unrelated species—often as biologically alien as a virus or a fish. Their modifications are designed primarily to boost profit margins for mechanized agribusiness: allowing crops to withstand herbicides so that weeds can be controlled by mass spraying, for example, or to produce their own pesticides to lessen the need for chemical inputs.
In the early days, the majority of GM crops were created by extracting the gene for a desired trait from a donor organism, multiplying it, and attaching it to other snippets of DNA—usually from a microbe called an agrobacterium—that could help it infiltrate the cells of the target plant. Biotechnologists injected these particles into the target, hoping at least one would land in a place where it would perform its intended function; if not, they kept trying. The process was quicker than conventional breeding, but still complex, scattershot, and costly.
Because agrobacteria can cause plant tumors, Kuzma explains, policymakers in the U.S. decided to regulate GMO crops under an existing law, the Plant Pest Act of 1957, which addressed dangers like imported trees infested with invasive bugs. Every GMO containing the DNA of agrobacterium or another plant pest had to be tested to see whether it behaved like a pest, and undergo a lengthy approval process. By 2010, however, new methods had been developed for creating GMOs without agrobacteria; such plants could typically be marketed without pre-approval.
Soon after that, the first gene-edited crops began appearing. If old-school genetic engineering was a shotgun, techniques like TALEN and CRISPR were a scalpel—or the search-and-replace function on a computer program. With CRISPR/Cas9, for example, an enzyme that bacteria use to recognize and chop up hostile viruses is reprogrammed to find and snip out a desired bit of a plant or other organism's DNA. The enzyme can also be used to insert a substitute gene. If a DNA sequence is simply removed, or the new gene comes from a similar species, the changes in the target plant's genotype and phenotype (its general characteristics) may be no different from those that could be produced through selective breeding. If a foreign gene is added, the plant becomes a transgenic GMO.
Companies are already teeing up gene-edited products for the U.S. market, like a cooking oil and waxy corn.
This development, along with the emergence of non-agrobacterium GMOs, eventually prompted the USDA to propose a tiered regulatory system for all genetically engineered crops, beginning with an initial screening for potentially hazardous metaboloids or ecological impacts. (The screening was intended, in part, to guard against the "off-target effects"—stray mutations—that occasionally appear in gene-edited organisms.) If no red flags appeared, the crop would be approved; otherwise, it would be subject to further review, and possible regulation.
The plan was unveiled in January 2017, during the last week of the Obama presidency. Then, under the Trump administration, it was shelved. Although the USDA continues to promise a new set of regulations, the only hint of what they might contain has been Secretary of Agriculture Sonny Perdue's statement last March that gene-edited plants would remain unregulated if they "could otherwise have been developed through traditional breeding techniques, as long as they are not plant pests or developed using plant pests."
Because transgenic plants could not be "developed through traditional breeding techniques," this statement could be taken to mean that gene editing in which foreign DNA is introduced might actually be regulated. But because the USDA regulates conventional transgenic GMOs only if they trigger the plant-pest stipulation, experts assume gene-edited crops will face similarly limited oversight.
Meanwhile, companies are already teeing up gene-edited products for the U.S. market. An herbicide-resistant oilseed rape, developed using a proprietary technique, has been available since 2016. A cooking oil made from TALEN-tweaked soybeans, designed to have a healthier fatty-acid profile, is slated for release within the next few months. A CRISPR-edited "waxy" corn, designed with a starch profile ideal for processed foods, should be ready by 2021.
In all likelihood, none of these products will have to be tested for safety.
In the E.U., Stricter Rules Apply
Now let's look at the European Union. Since the late 1990s, explains Gregory Jaffe, director of the Project on Biotechnology at the Center for Science in the Public Interest, the EU has had a "process-based trigger" for genetically engineered products: "If you use recombinant DNA, you are going to be regulated." All foods and animal feeds must be approved and labeled if they consist of or contain more than 0.9 percent GM ingredients. (In the U.S., "disclosure" of GM ingredients is mandatory, if someone asks, but labeling is not required.) The only GM crop that can be commercially grown in EU member nations is a type of insect-resistant corn, though some countries allow imports.
European scientists helped develop gene editing, and they—along with the continent's biotech entrepreneurs—have been busy developing applications for crops. But European farmers seem more divided over the technology than their American counterparts. The main French agricultural trades union, for example, supports research into non-transgenic gene editing and its exemption from GMO regulation. But it was the country's small-farmers' union, the Confédération Paysanne, along with several allied groups, that in 2015 submitted a complaint to the ECJ, asking that all plants produced via mutagenesis—including gene-editing—be regulated as GMOs.
At this point, it should be mentioned that in the past 30 years, large population studies have found no sign that consuming GM foods is harmful to human health. GMO critics can, however, point to evidence that herbicide-resistant crops have encouraged overuse of herbicides, giving rise to poison-proof "superweeds," polluting the environment with suspected carcinogens, and inadvertently killing beneficial plants. Those allegations were key to the French plaintiffs' argument that gene-edited crops might similarly do unexpected harm. (Disclosure: Leapsmag's parent company, Bayer, recently acquired Monsanto, a maker of herbicides and herbicide-resistant seeds. Also, Leaps by Bayer, an innovation initiative of Bayer and Leapsmag's direct founder, has funded a biotech startup called JoynBio that aims to reduce the amount of nitrogen fertilizer required to grow crops.)
The ruling was "scientifically nonsensical. It's because of things like this that I'll never go back to Europe."
In the end, the EU court found in the Confédération's favor on gene editing—though the court maintained the regulatory exemption for mutagenesis induced by chemicals or radiation, citing the 'long safety record' of those methods.
The ruling was "scientifically nonsensical," fumes Rodolphe Barrangou, a French food scientist who pioneered CRISPR while working for DuPont in Wisconsin and is now a professor at NC State. "It's because of things like this that I'll never go back to Europe."
Nonetheless, the decision was consistent with longstanding EU policy on crops made with recombinant DNA. Given the difficulty and expense of getting such products through the continent's regulatory system, many other European researchers may wind up following Barrangou to America.
Getting to the Root of the Cultural Divide
What explains the divergence between the American and European approaches to GMOs—and, by extension, gene-edited crops? In part, Jennifer Kuzma speculates, it's that Europeans have a different attitude toward eating. "They're generally more tied to where their food comes from, where it's produced," she notes. They may also share a mistrust of government assurances on food safety, borne of the region's Mad Cow scandals of the 1980s and '90s. In Catholic countries, consumers may have misgivings about tinkering with the machinery of life.
But the principal factor, Kuzma argues, is that European and American agriculture are structured differently. "GM's benefits have mostly been designed for large-scale industrial farming and commodity crops," she says. That kind of farming is dominant in the U.S., but not in Europe, leading to a different balance of political power. In the EU, there was less pressure on decisionmakers to approve GMOs or exempt gene-edited crops from regulation—and more pressure to adopt a GM-resistant stance.
Such dynamics may be operating in other regions as well. In China, for example, the government has long encouraged research in GMOs; a state-owned company recently acquired Syngenta, a Swiss-based multinational corporation that is a leading developer of GM and gene-edited crops. GM animal feed and cooking oil can be freely imported. Yet commercial cultivation of most GM plants remains forbidden, out of deference to popular suspicions of genetically altered food. "As a new item, society has debates and doubts on GMO techniques, which is normal," President Xi Jinping remarked in 2014. "We must be bold in studying it, [but] be cautious promoting it."
The proper balance between boldness and caution is still being worked out all over the world. Europe's process-based approach may prevent researchers from developing crops that, with a single DNA snip, could rescue millions from starvation. EU regulations will also make it harder for small entrepreneurs to challenge Big Ag with a technology that, as Barrangou puts it, "can be used affordably, quickly, scalably, by anyone, without even a graduate degree in genetics." America's product-based approach, conversely, may let crops with hidden genetic dangers escape detection. And by refusing to investigate such risks, regulators may wind up exacerbating consumers' doubts about GM and gene-edited products, rather than allaying them.
"Science...can't tell you what to regulate. That's a values-based decision."
Perhaps the solution lies in combining both approaches, and adding some flexibility and nuance to the mix. "I don't believe in regulation by the product or the process," says CSPI's Jaffe. "I think you need both." Deleting a DNA base pair to silence a gene, for example, might be less risky than inserting a foreign gene into a plant—unless the deletion enables the production of an allergen, and the transgene comes from spinach.
Kuzma calls for the creation of "cooperative governance networks" to oversee crop genome editing, similar to bodies that already help develop and enforce industry standards in fisheries, electronics, industrial cleaning products, and (not incidentally) organic agriculture. Such a network could include farmers, scientists, advocacy groups, private companies, and governmental agencies. "Safety isn't an all-or-nothing concept," Kuzma says. "Science can tell you what some of the issues are in terms of risk and benefit, but it can't tell you what to regulate. That's a values-based decision."
By drawing together a wide range of stakeholders to make such decisions, she adds, "we're more likely to anticipate future consequences, and to develop a robust approach—one that not only seems more legitimate to people, but is actually just plain old better."
The glass-encased cabinet looks like a display meant to hold reasonably priced watches, or drugstore beauty creams shipped from France. But instead of this stagnant merchandise, each of its five shelves is overgrown with leaves — moss-soft pea sprouts, spikes of Lolla rosa lettuces, pale bok choy, dark kale, purple basil or red-veined sorrel or green wisps of dill. The glass structure isn’t a cabinet, but rather a “micro farm.”
The gadget is on display at the Richmond, Virginia headquarters of Babylon Micro-Farms, a company that aims to make indoor farming in the U.S. more accessible and sustainable. Babylon’s soilless hydroponic growing system, which feeds plants via nutrient-enriched water, allows chefs on cruise ships, cafeterias and elsewhere to provide home-grown produce to patrons, just seconds after it’s harvested. Currently, there are over 200 functioning systems, either sold or leased to customers, and more of them are on the way.
The chef-farmers choose from among 45 types of herb and leafy-greens seeds, plop them into grow trays, and a few weeks later they pick and serve. While success is predicated on at least a small amount of these humans’ care, the systems are autonomously surveilled round-the-clock from Babylon’s base of operations. And artificial intelligence is helping to run the show.
Babylon piloted the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off.
Imagine consistently perfect greens and tomatoes and strawberries, grown hyper-locally, using less water, without chemicals or environmental contaminants. This is the hefty promise of controlled environment agriculture (CEA) — basically, indoor farms that can be hydroponic, aeroponic (plant roots are suspended and fed through misting), or aquaponic (where fish play a role in fertilizing vegetables). But whether they grow 4,160 leafy-green servings per year, like one Babylon farm, or millions of servings, like some of the large, centralized facilities starting to supply supermarkets across the U.S., they seek to minimize failure as much as possible.
Babylon’s soilless hydroponic growing system
Courtesy Babylon Micro-Farms
Here, AI is starting to play a pivotal role. CEA growers use it to help “make sense of what’s happening” to the plants in their care, says Scott Lowman, vice president of applied research at the Institute for Advanced Learning and Research (IALR) in Virginia, a state that’s investing heavily in CEA companies. And although these companies say they’re not aiming for a future with zero human employees, AI is certainly poised to take a lot of human farming intervention out of the equation — for better and worse.
Most of these companies are compiling their own data sets to identify anything that might block the success of their systems. Babylon had already integrated sensor data into its farms to measure heat and humidity, the nutrient content of water, and the amount of light plants receive. Last year, they got a National Science Foundation grant that allowed them to pilot the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off. “Will this plant be healthy tomorrow? Are there things…that the human eye can't see that the plant starts expressing?” says Amandeep Ratte, the company’s head of data science. “If our system can say, Hey, this plant is unhealthy, we can reach out to [users] preemptively about what they’re doing wrong, or is there a disease at the farm?” Ratte says. The earlier the better, to avoid crop failures.
Natural light accounts for 70 percent of Greenswell Growers’ energy use on a sunny day.
Courtesy Greenswell Growers
IALR’s Lowman says that other CEA companies are developing their AI systems to account for the different crops they grow — lettuces come in all shapes and sizes, after all, and each has different growing needs than, for example, tomatoes. The ways they run their operations differs also. Babylon is unusual in its decentralized structure. But centralized growing systems with one main location have variabilities, too. AeroFarms, which recently declared bankruptcy but will continue to run its 140,000-square foot vertical operation in Danville, Virginia, is entirely enclosed and reliant on the intense violet glow of grow lights to produce microgreens.
Different companies have different data needs. What data is essential to AeroFarms isn’t quite the same as for Greenswell Growers located in Goochland County, Virginia. Raising four kinds of lettuce in a 77,000-square-foot automated hydroponic greenhouse, the vagaries of naturally available light, which accounts for 70 percent of Greenswell’s energy use on a sunny day, affect operations. Their tech needs to account for “outside weather impacts,” says president Carl Gupton. “What adjustments do we have to make inside of the greenhouse to offset what's going on outside environmentally, to give that plant optimal conditions? When it's 85 percent humidity outside, the system needs to do X, Y and Z to get the conditions that we want inside.”
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen.
Nevertheless, every CEA system has the same core needs — consistent yield of high quality crops to keep up year-round supply to customers. Additionally, “Everybody’s got the same set of problems,” Gupton says. Pests may come into a facility with seeds. A disease called pythium, one of the most common in CEA, can damage plant roots. “Then you have root disease pressures that can also come internally — a change in [growing] substrate can change the way the plant performs,” Gupton says.
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen. So, while companies amass their own hyper-specific data sets, Lowman foresees a time within the next decade “when there will be some type of [open-source] database that has the most common types of plant stress identified” that growers will be able to tap into. Such databases will “create a community and move the science forward,” says Lowman.
In fact, IALR is working on assembling images for just such a database now. On so-called “smart tables” inside an Institute lab, a team is growing greens and subjects them to various stressors. Then, they’re administering treatments while taking images of every plant every 15 minutes, says Lowman. Some experiments generate 80,000 images; the challenge lies in analyzing and annotating the vast trove of them, marking each one to reflect outcome—for example increasing the phosphate delivery and the plant’s response to it. Eventually, they’ll be fed into AI systems to help them learn.
For all the enthusiasm surrounding this technology, it’s not without downsides. Training just one AI system can emit over 250,000 pounds of carbon dioxide, according to MIT Technology Review. AI could also be used “to enhance environmental benefit for CEA and optimize [its] energy consumption,” says Rozita Dara, a computer science professor at the University of Guelph in Canada, specializing in AI and data governance, “but we first need to collect data to measure [it].”
The chef-farmers can choose from 45 types of herb and leafy-greens seeds.
Courtesy Babylon Micro-Farms
Any system connected to the Internet of Things is also vulnerable to hacking; if CEA grows to the point where “there are many of these similar farms, and you're depending on feeding a population based on those, it would be quite scary,” Dara says. And there are privacy concerns, too, in systems where imaging is happening constantly. It’s partly for this reason, says Babylon’s Ratte, that the company’s in-farm cameras all “face down into the trays, so the only thing [visible] is pictures of plants.”
Tweaks to improve AI for CEA are happening all the time. Greenswell made its first harvest in 2022 and now has annual data points they can use to start making more intelligent choices about how to feed, water, and supply light to plants, says Gupton. Ratte says he’s confident Babylon’s system can already “get our customers reliable harvests. But in terms of how far we have to go, it's a different problem,” he says. For example, if AI could detect whether the farm is mostly empty—meaning the farm’s user hasn’t planted a new crop of greens—it can alert Babylon to check “what's going on with engagement with this user?” Ratte says. “Do they need more training? Did the main person responsible for the farm quit?”
Lowman says more automation is coming, offering greater ability for systems to identify problems and mitigate them on the spot. “We still have to develop datasets that are specific, so you can have a very clear control plan, [because] artificial intelligence is only as smart as what we tell it, and in plant science, there's so much variation,” he says. He believes AI’s next level will be “looking at those first early days of plant growth: when the seed germinates, how fast it germinates, what it looks like when it germinates.” Imaging all that and pairing it with AI, “can be a really powerful tool, for sure.”
Story by Big Think
For over a century, scientists have dreamed of growing human organs sans humans. This technology could put an end to the scarcity of organs for transplants. But that’s just the tip of the iceberg. The capability to grow fully functional organs would revolutionize research. For example, scientists could observe mysterious biological processes, such as how human cells and organs develop a disease and respond (or fail to respond) to medication without involving human subjects.
Recently, a team of researchers from the University of Cambridge has laid the foundations not just for growing functional organs but functional synthetic embryos capable of developing a beating heart, gut, and brain. Their report was published in Nature.
The organoid revolution
In 1981, scientists discovered how to keep stem cells alive. This was a significant breakthrough, as stem cells have notoriously rigorous demands. Nevertheless, stem cells remained a relatively niche research area, mainly because scientists didn’t know how to convince the cells to turn into other cells.
Then, in 1987, scientists embedded isolated stem cells in a gelatinous protein mixture called Matrigel, which simulated the three-dimensional environment of animal tissue. The cells thrived, but they also did something remarkable: they created breast tissue capable of producing milk proteins. This was the first organoid — a clump of cells that behave and function like a real organ. The organoid revolution had begun, and it all started with a boob in Jello.
For the next 20 years, it was rare to find a scientist who identified as an “organoid researcher,” but there were many “stem cell researchers” who wanted to figure out how to turn stem cells into other cells. Eventually, they discovered the signals (called growth factors) that stem cells require to differentiate into other types of cells.
For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells.
By the end of the 2000s, researchers began combining stem cells, Matrigel, and the newly characterized growth factors to create dozens of organoids, from liver organoids capable of producing the bile salts necessary for digesting fat to brain organoids with components that resemble eyes, the spinal cord, and arguably, the beginnings of sentience.
Organoids possess an intrinsic flaw: they are organ-like. They share some characteristics with real organs, making them powerful tools for research. However, no one has found a way to create an organoid with all the characteristics and functions of a real organ. But Magdalena Żernicka-Goetz, a developmental biologist, might have set the foundation for that discovery.
Żernicka-Goetz hypothesized that organoids fail to develop into fully functional organs because organs develop as a collective. Organoid research often uses embryonic stem cells, which are the cells from which the developing organism is created. However, there are two other types of stem cells in an early embryo: stem cells that become the placenta and those that become the yolk sac (where the embryo grows and gets its nutrients in early development). For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells. In other words, Żernicka-Goetz suspected the best way to grow a functional organoid was to produce a synthetic embryoid.
As described in the aforementioned Nature paper, Żernicka-Goetz and her team mimicked the embryonic environment by mixing these three types of stem cells from mice. Amazingly, the stem cells self-organized into structures and progressed through the successive developmental stages until they had beating hearts and the foundations of the brain.
“Our mouse embryo model not only develops a brain, but also a beating heart [and] all the components that go on to make up the body,” said Żernicka-Goetz. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years and major focus of our work for a decade and finally we’ve done it.”
If the methods developed by Żernicka-Goetz’s team are successful with human stem cells, scientists someday could use them to guide the development of synthetic organs for patients awaiting transplants. It also opens the door to studying how embryos develop during pregnancy.