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."
When David M. Kurtz was doing his clinical fellowship at Stanford University Medical Center in 2009, specializing in lymphoma treatments, he found himself grappling with a question no one could answer. A typical regimen for these blood cancers prescribed six cycles of chemotherapy, but no one knew why. "The number seemed to be drawn out of a hat," Kurtz says. Some patients felt much better after just two doses, but had to endure the toxic effects of the entire course. For some elderly patients, the side effects of chemo are so harsh, they alone can kill. Others appeared to be cancer-free on the CT scans after the requisite six but then succumbed to it months later.
"Anecdotally, one patient decided to stop therapy after one dose because he felt it was so toxic that he opted for hospice instead," says Kurtz, now an oncologist at the center. "Five years down the road, he was alive and well. For him, just one dose was enough." Others would return for their one-year check up and find that their tumors grew back. Kurtz felt that while CT scans and MRIs were powerful tools, they weren't perfect ones. They couldn't tell him if there were any cancer cells left, stealthily waiting to germinate again. The scans only showed the tumor once it was back.
Blood cancers claim about 68,000 people a year, with a new diagnosis made about every three minutes, according to the Leukemia Research Foundation. For patients with B-cell lymphoma, which Kurtz focuses on, the survival chances are better than for some others. About 60 percent are cured, but the remaining 40 percent will relapse—possibly because they will have a negative CT scan, but still harbor malignant cells. "You can't see this on imaging," says Michael Green, who also treats blood cancers at University of Texas MD Anderson Medical Center.
The new blood test is sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
Kurtz wanted a better diagnostic tool, so he started working on a blood test that could capture the circulating tumor DNA or ctDNA. For that, he needed to identify the specific mutations typical for B-cell lymphomas. Working together with another fellow PhD student Jake Chabon, Kurtz finally zeroed-in on the tumor's genetic "appearance" in 2017—a pair of specific mutations sitting in close proximity to each other—a rare and telling sign. The human genome contains about 3 billion base pairs of nucleotides—molecules that compose genes—and in case of the B-cell lymphoma cells these two mutations were only a few base pairs apart. "That was the moment when the light bulb went on," Kurtz says.
The duo formed a company named Foresight Diagnostics, focusing on taking the blood test to the clinic. But knowing the tumor's mutational signature was only half the process. The other was fishing the tumor's DNA out of patients' bloodstream that contains millions of other DNA molecules, explains Chabon, now Foresight's CEO. It would be like looking for an escaped criminal in a large crowd. Kurtz and Chabon solved the problem by taking the tumor's "mug shot" first. Doctors would take the biopsy pre-treatment and sequence the tumor, as if taking the criminal's photo. After treatments, they would match the "mug shot" to all DNA molecules derived from the patient's blood sample to see if any molecular criminals managed to escape the chemo.
Foresight isn't the only company working on blood-based tumor detection tests, which are dubbed liquid biopsies—other companies such as Natera or ArcherDx developed their own. But in a recent study, the Foresight team showed that their method is significantly more sensitive in "fishing out" the cancer molecules than existing tests. Chabon says that this test can detect circulating tumor DNA in concentrations that are nearly 100 times lower than other methods. Put another way, it's sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
"It increases the sensitivity of detection and really catches most patients who are going to progress," says Green, the University of Texas oncologist who wasn't involved in the study, but is familiar with the method. It would also allow monitoring patients during treatment and making better-informed decisions about which therapy regimens would be most effective. "It's a minimally invasive test," Green says, and "it gives you a very high confidence about what's going on."
Having shown that the test works well, Kurtz and Chabon are planning a new trial in which oncologists would rely on their method to decide when to stop or continue chemo. They also aim to extend their test to detect other malignancies such as lung, breast or colorectal cancers. The latest genome sequencing technologies have sequenced and catalogued over 2,500 different tumor types, says Chabon, which gives the team the opportunity to create more molecular "mug shots."
The team hopes that that their blood cancer test will become available to patients within about five years, making doctors' job easier, and not only at the biological level. "When I tell patients, "good news, your cancer is in remission', they ask me, 'does it mean I'm cured?'" Kurtz says. "Right now I can't answer this question because I don't know—but I would like to." His company's test, he hopes, will enable him to reply with certainty. He'd very much like to have the power of that foresight.
The white two-seater car that rolls down the street in the Sorrento Valley of San Diego looks like a futuristic batmobile, with its long aerodynamic tail and curved underbelly. Called 'Sol' (Spanish for "sun"), it runs solely on solar and could be the future of green cars. Its maker, the California startup Aptera, has announced the production of Sol, the world's first mass-produced solar vehicle, by the end of this year. Aptera co-founder Chris Anthony points to the sky as he says, "On this sunny California day, there is ample fuel. You never need to charge the car."
If you live in a sunny state like California or Florida, you might never need to plug in the streamlined Sol because the solar panels recharge while driving and parked. Its 60-mile range is more than the average commuter needs. For cloudy weather, battery packs can be recharged electronically for a range of up to 1,000 miles. The ultra-aerodynamic shape made of lightweight materials such as carbon, Kevlar, and hemp makes the Sol four times more energy-efficient than a Tesla, according to Aptera. "The material is seven times stronger than steel and even survives hail or an angry ex-girlfriend," Anthony promises.
Co-founder Steve Fambro opens the Sol's white doors that fly upwards like wings and I get inside for a test drive. Two dozen square solar panels, each the size of a large square coaster, on the roof, front, and tail power the car. The white interior is spartan; monitors have replaced mirrors and the dashboard. An engineer sits in the driver's seat, hits the pedal, and the low-drag two-seater zooms from 0 to 60 in 3.5 seconds.
It feels like sitting in a race car because the two-seater is so low to the ground but the car is built to go no faster than 100 or 110 mph. The finished car will weigh less than 1,800 pounds, about half of the smallest Tesla. The average car, by comparison, weighs more than double that. "We've built it primarily for energy efficiency," Steve Fambro says, explaining why the Sol has only three wheels. It's technically an "auto-cycle," a hybrid between a motorcycle and a car, but Aptera's designers are also working to design a four-seater.
There has never been a lack of grand visions for the future of the automobile, but until these solar cars actually hit the streets, nobody knows how the promises will hold up.
Transportation is currently the biggest source of greenhouse gases. Developing an efficient solar car that does not burden the grid has been the dream of innovators for decades. Every other year, dozens of innovators race their self-built solar cars 2,000 miles through the Australian desert.
More effective solar panels are finally making the dream mass-compatible, but just like other innovative car ideas, Aptera's vision has been plagued with money problems. Anthony and Fambro were part of the original crew that founded Aptera in 2006 and worked on the first prototype around the same time Tesla built its first roadster, but Aptera went bankrupt in 2011. Anthony and Fambro left a year before the bankruptcy and went on to start other companies. Among other projects, Fambro developed the first USDA organic vertical farm in the United Arab Emirates, and Anthony built a lithium battery company, before the two decided to buy Aptera back. Without a billionaire such as Elon Musk bankrolling the risky process of establishing a whole new car production system from scratch, the huge production costs are almost insurmountable.
But Aptera's founders believe they have found solutions for the entire production process as well as the car design. Most parts of the Sol's body can be made by 3D printers and assembled like a Lego kit. If this makes you think of a toy car, Anthony assures potential buyers that the car aced stress tests and claims it's safer than any vehicle on the market, "because the interior is shaped like an egg and if there is an impact, the pressure gets distributed equally." However, Aptera has yet to release crash test safety data so outside experts cannot evaluate their claims.
Instead of building a huge production facility, Anthony and Fambro envision "micro-factories," each less than 10,000 square feet, where a small crew can assemble cars on demand wherever the orders are highest, be it in California, Canada, or China.
If a part of the Sol breaks, Aptera promises to send replacement parts to any corner of the world within 24 hours, with instructions. So a mechanic in a rural corner in Arkansas or China who never worked on a solar car before simply needs to download the instructions and replace the broken part. At least that's the idea. "The material does not rust nor fatigue," Fambro promises. "You can pass the car onto your grandchildren. When more efficient solar panels hit the market, we simply replace them."
More than 11,000 potential buyers have already signed up; the cheapest model costs around $26,000 USD and Aptera expects the first cars to ship by the end of the year.
Two other solar carmakers are vying for the pole position in the race to be the first to market: The German startup Sono has also announced it will also produce its first solar car by the end of this year. The price tag for the basic model is also around $26,000, but its concept is very different. From the outside, the Sion looks like a conservative minivan for a family; only a closer look reveals that the dark exterior is made of solar panels. Sono, too, nearly went bankrupt a few years ago and was saved through a crowdfunding campaign by enthusiastic fans.
Meanwhile, Norwegian company Lightyear wants to produce a sleek solar-powered luxury sedan by the end of the year, but its price of around $180,000 makes it unaffordable for most buyers.
There has never been a lack of grand visions for the future of the automobile, but until these solar cars actually hit the streets, nobody knows how the promises will hold up. How often will the cars need to be repaired? What happens when snow and ice cover the solar panels? Also, you can't park the car in a garage if you need the sun to charge it.
Critics, including students at the Solar Car team at the University of Michigan, say that mounting solar panels on a moving vehicle will never yield the most efficient results compared to static panels. Also, they are quick to point out that no company has managed to overcome the production hurdles yet. Others in the field also wonder how well the solar panels will actually work.
"It's important to realize that the solar mileage claims by these companies are likely the theoretical best case scenario but in the real world, solar range will be significantly less when you factor in shading, parking in garages, and geographies with lower solar irradiance," says Evan Stumpges, the team coordinator for the American Solar Challenge, a competition in which enthusiasts build and race solar-powered cars. "The encouraging thing is that I have seen videos of real working prototypes for each of these vehicles which is a key accomplishment. That said, I believe the biggest hurdle these companies have yet to face is successfully ramping up to volume production and understanding what their profitability point will be for selling the vehicles once production has stabilized."
Professor Daniel M. Kammen, the founding director of the Renewable and Appropriate Energy Laboratory at the University of California, Berkeley, and one of the world's foremost experts on renewable energy, believes that the technical challenges have been solved, and that solar cars have real advantages over electric vehicles.
"This is the right time to be bullish. Cutting out the charging is a natural solution for long rides," he says. "These vehicles are essentially solar panels and batteries on wheels. These are now record low-cost and can be built from sustainable materials." Apart from Aptera's no-charge technology, he appreciates the move toward no-conflict materials. "Not only is the time ripe but the youth movement is pushing toward conflict-free material and reducing resource waste....A low-cost solar fleet could be really interesting in relieving burden on the grid, or you could easily imagine a city buying a bunch of them and connecting them with mass transit." While he has followed all three new solar companies with interest, he has already ordered an Aptera car for himself, "because it's American and it looks the most different."
After taking a spin in the Sol, it is startling to switch back into a regular four-seater. Rolling out of Aptera's parking lot onto the freeway next to all the oversized gas guzzlers that need to stop every couple of hundreds of miles to fill up, one can't help but think: We've just taken a trip into the future.