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."
What to Know about the Fast-Spreading Delta Variant
A highly contagious form of the coronavirus known as the Delta variant is spreading rapidly and becoming increasingly prevalent around the world. First identified in India in December, Delta has now been identified in 111 countries.
In the United States, the variant now accounts for 83% of sequenced COVID-19 cases, said Rochelle Walensky, director of the Centers for Disease Control and Prevention, at a July 20 Senate hearing. In May, Delta was responsible for just 3% of U.S. cases. The World Health Organization projects that Delta will become the dominant variant globally over the coming months.
So, how worried should you be about the Delta variant? We asked experts some common questions about Delta.
What is a variant?
To understand Delta, it's helpful to first understand what a variant is. When a virus infects a person, it gets into your cells and makes a copy of its genome so it can replicate and spread throughout your body.
In the process of making new copies of itself, the virus can make a mistake in its genetic code. Because viruses are replicating all the time, these mistakes — also called mutations — happen pretty often. A new variant emerges when a virus acquires one or more new mutations and starts spreading within a population.
There are thousands of SARS-CoV-2 variants, but most of them don't substantially change the way the virus behaves. The variants that scientists are most interested in are known as variants of concern. These are versions of the virus with mutations that allow the virus to spread more easily, evade vaccines, or cause more severe disease.
"The vast majority of the mutations that have accumulated in SARS-CoV-2 don't change the biology as far as we're concerned," said Jennifer Surtees, a biochemist at the University of Buffalo who's studying the coronavirus. "But there have been a handful of key mutations and combinations of mutations that have led to what we're now calling variants of concern."
One of those variants of concern is Delta, which is now driving many new COVID-19 infections.
Why is the Delta variant so concerning?
"The reason why the Delta variant is concerning is because it's causing an increase in transmission," said Alba Grifoni, an infectious disease researcher at the La Jolla Institute for Immunology. "The virus is spreading faster and people — particularly those who are not vaccinated yet — are more prone to exposure."
The Delta variant has a few key mutations that make it better at attaching to our cells and evading the neutralizing antibodies in our immune system. These mutations have changed the virus enough to make it more than twice as contagious as the original SARS-CoV-2 virus that emerged in Wuhan and about 50% more contagious than the Alpha variant, previously known as B.1.1.7, or the U.K. variant.
These mutations were previously seen in other variants on their own, but it's their combination that makes Delta so much more infectious.
Do vaccines work against the Delta variant?
The good news is, the COVID-19 vaccines made by AstraZeneca, Johnson & Johnson, Moderna, and Pfizer still work against the Delta variant. They remain more than 90% effective at preventing hospitalizations and death due to Delta. While they're slightly less protective against disease symptoms, they're still very effective at preventing severe illness caused by the Delta variant.
"They're not as good as they were against the prior strains, but they're holding up pretty well," said Eric Topol, a physician and director of the Scripps Translational Research Institute, during a July 19 briefing for journalists.
Because Delta is better at evading our immune systems, it's likely causing more breakthrough infections — COVID-19 cases in people who are vaccinated. However, breakthrough infections were expected before the Delta variant became widespread. No vaccine is 100% effective, so breakthrough infections can happen with other vaccines as well. Experts say the COVID-19 vaccines are still working as expected, even if breakthrough infections occur. The majority of these infections are asymptomatic or cause only mild symptoms.
Should vaccinated people worry about the Delta variant?
Vaccines train our immune systems to protect us against infection. They do this by spurring the production of antibodies, which stick around in our bodies to help fight off a particular pathogen in case we ever come into contact with it.
But even if the new Delta variant slips past our neutralizing antibodies, there's another component of our immune system that can help overtake the virus: T cells. Studies are showing that the COVID-19 vaccines also galvanize T cells, which help limit disease severity in people who have been vaccinated.
"While antibodies block the virus and prevent the virus from infecting cells, T cells are able to attack cells that have already been infected," Grifoni said. In other words, T cells can prevent the infection from spreading to more places in the body. A study published July 1 by Grifoni and her colleagues found that T cells were still able to recognize mutated forms of the virus — further evidence that our current vaccines are effective against Delta.
Can fully vaccinated people spread the Delta variant?
Previously, scientists believed it was unlikely for fully vaccinated individuals with asymptomatic infections to spread Covid-19. But the Delta variant causes the virus to make so many more copies of itself inside the body, and high viral loads have been found in the respiratory tracts of people who are fully vaccinated. This suggests that vaccinated people may be able to spread the Delta variant to some degree.
If you have COVID-19 symptoms, even if you're fully vaccinated, you should get tested and isolate from friends and family because you could spread the virus.
What risk does Delta pose to unvaccinated people?
The Delta variant is behind a surge in cases in communities with low vaccination rates, and unvaccinated Americans currently account for 97% of hospitalizations due to COVID-19, according to Walensky. The best thing you can do right now to prevent yourself from getting sick is to get vaccinated.
Gigi Gronvall, an immunologist and senior scholar at the Johns Hopkins Center for Health Security, said in this week's "Making Sense of Science" podcast that it's especially important to get all required doses of the vaccine in order to have the best protection against the Delta variant. "Even if it's been more than the allotted time that you were told to come back and get the second, there's no time like the present," she said.
With more than 3.6 billion COVID-19 doses administered globally, the vaccines have been shown to be incredibly safe. Serious adverse effects are rare, although scientists continue to monitor for them.
Being vaccinated also helps prevent the emergence of new and potentially more dangerous variants. Viruses need to infect people in order to replicate, and variants emerge because the virus continues to infect more people. More infections create more opportunities for the virus to acquire new mutations.
Surtees and others worry about a scenario in which a new variant emerges that's even more transmissible or resistant to vaccines. "This is our window of opportunity to try to get as many people vaccinated as possible and get people protected so that so that the virus doesn't evolve to be even better at infecting people," she said.
Does Delta cause more severe disease?
While hospitalizations and deaths from COVID-19 are increasing again, it's not yet clear whether Delta causes more severe illness than previous strains.
How can we protect unvaccinated children from the Delta variant?
With children 12 and under not yet eligible for the COVID-19 vaccine, kids are especially vulnerable to the Delta variant. One way to protect unvaccinated children is for parents and other close family members to get vaccinated.
It's also a good idea to keep masks handy when going out in public places. Due to risk Delta poses, the American Academy of Pediatrics issued new guidelines July 19 recommending that all staff and students over age 2 wear face masks in school this fall, even if they have been vaccinated.
Parents should also avoid taking their unvaccinated children to crowded, indoor locations and make sure their kids are practicing good hand-washing hygiene. For children younger than 2, limit visits with friends and family members who are unvaccinated or whose vaccination status is unknown and keep up social distancing practices while in public.
While there's no evidence yet that Delta increases disease severity in children, parents should be mindful that in some rare cases, kids can get a severe form of the disease.
"We're seeing more children getting sick and we're seeing some of them get very sick," Surtees said. "Those children can then pass on the virus to other individuals, including people who are immunocompromised or unvaccinated."
New Podcast: Dr. Gigi Gronvall Addresses the Risk of Delta and COVID-19’s Possible Origins
"Making Sense of Science" is a monthly podcast that features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This episode is hosted by science and biotech journalist Emily Mullin, summer editor of the award-winning science outlet Leaps.org.