(Shutterstock, Pairwise | Photo-illustration by Bradley R. Hughes)

CRISPR Crops Are Here

Foods genetically edited using CRISPR technology are beginning to hit store shelves. How are they different from GMOs?

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16 hours ago

By Paolo Pontoniere

Had it been coined intentionally for the purpose of marketing fresh produce, the acronym CRISPR would have been a stroke of advertising genius. After all, who wouldn’t want their salad to be crisper?

But the true genius of this gene-editing technology could be its ability to jump straight to consumer shelves, sidestepping all the controversies that have tripped up its cousin GMO, with which it shares its biotechnological roots.

Clustered Regularly Interspaced Palindromic Repeats (CRISPR) allow researchers to genetically control organisms on a molecular basis — from bacteria and viruses to plants, insects, and larger animals up to and including humans. First described in 1987 by Yoshizumi Ishino at Osaka University, the technology seems wondrously applicable as a tool to help solve many of modern life’s problems — from human diseases to global warming. It has fueled new approaches for treating rare genetic diseases and common ailments like cancer, mostly without controversy.

So far, CRISPR crops have also avoided the societal stigma and outright legal bans that genetically modified organism (GMO) crops have faced, especially in Europe. But the true test of how the public will react is yet to come, as more and more CRISPR crops become consumer-ready.

Could CRISPR feed the world?

Nowhere is the human promise of CRISPR more apparent than in its potential for alleviating the scourge of world hunger.

The scope of the problem is massive. Some 2.3 billion people and counting face moderate food insecurity or outright starvation — this amounts to about 29 percent of the world’s population. Climate change, increased urbanization, and refugee crises inflicted by natural disasters or wars exacerbate this huge humanitarian problem. And the loss of arable land and the overuse of pesticides and fertilizers is pushing farming into unknown territory and increasingly encroaches on wilderness and wildlife. How we resolve these puzzles and learn to adapt food systems to adequately feed the planet has become a matter of human survival.

Proponents of CRISPR foods think they have the answer: crops and animals genetically edited to be heartier, thrive in more places, require fewer pesticides and fertilizers and water, survive longer on shelves, or make tastier or more nutritious produce.

A case in point is a new sweet gene-edited mustard green produced by the Durham, North Carolina-based food and agricultural company Pairwise. The new plant will soon be marketed in selected locations like Performance Food Group Company restaurants in Minnesota and the Monterey County food bank in California.

Using a proprietary enzyme to knock down a gene responsible for their asperity, Pairwise’s mustard greens have been CRISPR edited to be no more bitter than simple lettuce. Chock-full of nutrients, wild-type, unedited mustard greens are a simple, easy-to-grow dark leafy vegetable — but with a bitterness that can overwhelm the palate. As a result, recipes for this classic Southern staple often call for drowning it in ham fat, sugar, and vinegar and cooking it to death. Even then, the bitterness shines through. Adding to its edited product line, Pairwise is also planning to launch within a couple of years pit-free cherries, seedless blackberries, and other types of greens that will be better tasting and more nutritious.

CRISPR is not used to add any foreign genes into the edited organism — but rather to eliminate or correct unwanted genetic traits.

Pairwise’s scientific success follows the U.S. Food and Drug Administration’s (FDA) go-to-market approval of gene-edited cattle from the Eagan, Minnesota, biotech company Recombinetics. The company designed a way to genetically edit cows for a short-haired, “slick” coat trait, rendering the animals more resilient in the unforgiving high-noon heat of hot summer days. In developing countries alone, heat-related cattle deaths cause yearly losses of $400 million.

The very first CRISPR-edited food appeared on the consumer market in 2021 when Sanatech Seed, a Tokyo-based startup, began selling the Sicilian Rouge High GABA tomato to Japanese consumers. This variety of tomatoes contains high amounts of gamma-aminobutyric acid (GABA), a neurotransmitter produced naturally in several brain areas through a reaction in which glutamate — the body’s most abundant amino acid — is bound to vitamin B6 by glutamate decarboxylase. Foods naturally rich in GABA include tomatoes, beans, peas, mushrooms, and cruciferous vegetables. So Sanatech aims to boost the nutritionally available levels of GABA in an already GABA-rich tomato.

GABA is both the premier excitatory neurotransmitter in the developing brain and the main calming one in the mature one. Working hand-in-hand with glutamate, it regulates the inhibitory-excitatory balance necessary for the brain to experience optimal homeostasis or to return to a balanced state following intense neurostimulation. Dietary GABA has been linked to reduced anxiety, stress relief, insomnia relief, lower blood pressure, and improved cognition.

“Sicilian Rouge is a popular tomato, and consumers are already used to buying other products with a high GABA content,” Shimpei Takeshita, the president of Sanatech Seed, said in an interview when the tomatoes were introduced. “We felt it was important to introduce them to the technology in a way already familiar to them,” he explained.

The researchers did not add any exogenous gene to the tomatoes’ genome but just edited the tomato’s own GABA synthase enzyme to cause an increased conversion of glutamate. Confident that the company’s claims were verified, Japanese regulators decided that the fruit should not be labeled as a “genetically modified” crop.

CRISPR edited Sicilian Rouge tomatoes. (Sanatech)

How CRISPR works

Classic genetically modified organisms are plants injected with DNA sequences that engineer desirable traits sought by growers, like resistance to pests, tolerance of chemical weed killers, increased yield, or longer shelf-life. Those DNA sequences could come either from a different strain of the same crop or another organism altogether, so anti-GMO activists often deride them as “Frankenfoods.”

On the contrary, CRISPR is not used to add any foreign genes into the edited organism — but rather to eliminate or correct unwanted genetic traits like mutation-driven diseases in humans or unsavory tastes in mustard greens. It does that by leveraging the immune response of bacteria when viruses attack them.

When a virus attacks a bacteria, it records that event in its immune system and then produces a section of the virus’ DNA in its own genome, capping it with a repeating amino acid sequence called a CRISPR. By doing so, the bacteria essentially vaccinates itself against the invading virus. The next time the bacteria encounters the same virus, it unleashes a specific CRISPR-Cas9 protein that cuts the invading DNA, destroying it. In the case of CRISPR crops, researchers can create a particular DNA sequence matching the location of the DNA they want to cut. Once the DNA is cut, scientists can delete or modify the sequence causing the problem they seek to correct.

“It is wrong to compare GMO to CRISPR,” says Leena Tripathi, Ph.D. and Director of the Biotechnology Program at Nigeria’s International Institute of Tropical Agriculture (IITA). “Rather than manipulating, CRISPR works like natural breeding, just much faster. In general, it silences a negative trait to allow the increased expression of a positive trait in the same organism.”

Banana Xanthomonas wilt is a banana disease caused by the fungus Xanthomonas campestris, and it is considered one of the most destructive banana diseases in East and Central Africa. It exacerbates malnutrition, since many people in these regions rely on that crop for sustenance. Tripathi and colleagues are increasing banana resistance to the disease by precisely editing the ortholog DMR6, a protein which allows for the overexpression of the fruit’s own resistance mechanisms, making it vulnerable to the fungus. Orthologs genes are genes that are similar but present in different species. They descend directly from an ancestor that species shared during their past evolution.

Education is crucial for preventing consumers from associating CRISPR-edited foods with GMOs.

The FDA has mandated that gene-edited animals undergo pre-market evaluation in the United States. However, the U.S. Department of Agriculture announced in 2018 that CRISPR plants and farm animals would not fall under the agency’s regulations for genetically modified organisms as they don’t contain any added viral or bacterial DNA fragments. Furthermore, because the FDA considers them as food variations that would have naturally occurred in nature, it has decided that they don’t need to be labeled as either genetically modified or edited. Nevertheless, the team at Pairwise understands the need to adopt a consumer-friendly and culturally soft strategy to introduce consumers to gene-edited foods.

“We have a broader mission,” says Pairwise CEO and co-founder Tom Adams. “We’d really like to see people eat fruits and vegetables. And we recognize that there are some varieties of greens that have really good nutrition.”

That’s what led them to mustard greens. “They have a texture like lettuce, but they didn’t taste good,” Adams says. So they used CRISPR editing to remove the off-putting flavor of the green. Adams believes people tend to like the product first before understanding the technology, which is more critical for their success. Like laws and sausages, how foods are engineered may be much less palatable than how they taste.

Full seed ahead

Genetically modified foods are an everyday staple in the United States — almost the entire U.S. rapeseed crop (for canola oil), sugar beets, corn, soybeans, and cotton are grown from GMO strains. In Canada, 100 percent of the alfalfa is already genetically modified, and around the world, other GMO crops like potato, papaya, alfalfa, and squash are gaining ground. However, despite their growing global market penetration, GMO foods still remain unpopular with consumers. Many manufacturers of gene-edited food staples, like Pairwise’s Adams, believe that education is crucial for preventing consumers from associating CRISPR-edited foods with GMOs.

“I see CRISPR as a valuable tool that opens new areas of research,” says Saharah Moon Chapotin, the executive director of the Foundation for Food & Agriculture Research. “This tool can be used to develop crops and animals that farmers need to address pests and diseases and adapt to a changing climate while improving productivity and sustainability.”

However, the distinction between CRISPR and GMOs is more than just a mere matter of public opinion. Regulatory bodies are also still determining the safety of the technology in foods. For example, a U.S. Government Accountability Office document about the safety of CRISPR technology recently warned the public that unintended consequences exist, as with all technologies, hinting that even if the technology is reputed safe, it cannot be excluded that accidents may still happen.

Despite the debate, new CRISPR-edited foods will soon arrive on the global market. Using CRISPR, Chinese and German researchers increased the number of kernels per ear of corn from 14 to 16, which increased the yield by 10 percent. In rice, the same technique produced an 8 percent yield increase.

Argentinian researchers at the National Agricultural Technology Institute in Buenos Aires revealed that they’ve used CRISPR to silence a gene that resulted in potatoes with reduced browning. In California, the San Leandro-based SCiFi Foods has developed a line of cow cells that can grow into protein for burger patties that can be sold for less than $10. And recent advances in synthetic biology suggest that consistently growing these cells both for food and medicine is about to get a lot easier. Not surprisingly, investors are paying attention to the potential of CRISPR in agriculture and farming.

A hamburger made with cultured beef from SCiFi Foods. (SCiFi Foods)

“CRISPR can clearly have a positive impact on food productivity, quality, and environmental sustainability,” says Seth Yakatan, a partner at the Los Angeles-based Consulting and Merchant Banking firm Katan Associates. “As the global population continues to grow, and less land and water resources will be available to grow crops, CRISPR might be able to help.”

As the technology gains notoriety, however, other new worries are emerging. One specific concern is that CRISPR may interfere with natural evolution. This was highlighted as far back as 2017 in a Time magazine interview with Marcy Darnovsky, the executive director of the Center for Genetics and Society, a nonprofit social justice organization concerned with the future of humanity and reproduction in the face of emerging genetic engineering technologies. Darnovsky is quoted denouncing what she called the rise of “market-based eugenics,” by which she means that the sheer number of individual choices made to “improve” biological organisms could lead to weeding out unwanted traits from the gene pool.

And knowing that orthologs also mark the location where the related genomes begin the evolutionary divergence that will lead to the emergence of different species, she may be partially correct. Because even though CRISPR might be akin to Gregor Mandel’s early genetics work based on seed hybridization, as Tripathi at Nigeria’s International Institute of Tropical Agriculture explains, one must recognize that the elimination of some alleles, when well-placed, leads to the emergence of a new species. That is the case of the ortholog DMR6 edited banana which now will survive against the invading agent while its progenitor will not.

Editor’s note: This article was updated on 7/30/23 to correct Saharah Moon Chapotin’s affiliation and to describe, in the 13th paragraph, GABA’s action in the brain. It was updated on 8/4/23 to remove reference to the Arctic Apple, which was erroneously reported to be the first genetically edited produce using CRISPR.

Originally published at https://proto.life.