What is stopping gene-edited food from saving our planet?

Last month, a Ph.D. student at the Hebrew University of Jerusalem bred a new strain of supercharged lettuce that expanded its vitamin C and beta carotene content by 800 percent and 70 percent, respectively.

Yarin Livneh, working under Professor Alexander Vainstein, developed the proof-of-concept lettuce, which demonstrated that the nutritional qualities of lettuce could be increased using gene-editing techniques.

"Lettuce is assumed to be very healthy, but it is poor in nutrients when compared with other leafy vegetables," Livneh tells Interesting Engineering.

Leveraging the technology of CRISPR-Cas9, a transformative tool for editing genomes that permits the rapid alteration of DNA sequences and modification of gene function, she altered the regulatory components of the vegetable, essentially "tricking" the lettuce into accumulating more nutrients, for the benefit of consumers. 

Livneh's experiment is just one recent example enamored with the technology whose developers received a Nobel Prize in Chemistry in 2020. 

Last September, Tokyo-based Sanatech Seed began selling Sicilian Rouge tomatoes, which had been developed using gene editing to contain large amounts of γ-aminobutyric acid (GABA) to consumers. According to the company, the oral intake of GABA can help support lower blood pressure. The genome-edited fruit was approved by Japan's regulators in December 2020, after which the company sent free seedling CRISPR-edited tomato plants to about 4,200 home gardeners in May 2021.

There's more.

Scientists in the US and UK are working on modifying wheat to produce strains with lower amounts of gluten proteins, gliadins, which are known to cause celiac disease. Researchers have also used CRISPR to increase the number of kernels in corn. CRISPR crops could also be developed to become resistant to extreme weather patterns, pests, plant diseases and possibly use fewer resources like land, water, and fertilizers. The potential applications for the technology are aplenty, including curing genetic diseases in humans and even resurrecting extinct species. Over the past few years, the tool has revolutionized genome manipulation and redefined research in agriculture and medicine. 

Zoom out, and the picture looks almost surreal. Rodolphe Barrangou, a professor in probiotics research at North Carolina State University and the editor-in-chief of The CRISPR Journal, tells IE he's happy to see the speed.

"The pace at which this has happened is very impressive, refreshing, and inspiring," Barrangou says.

Some might argue that this gene-editing tool could help alleviate some of the carbon emissions from agriculture and reduce some types of food insecurity, along with traditional breeding and other techniques. But the road to a CRISPR future is littered with concerns about the environmental, health, and commercial impacts of GMO (genetically-modified organisms), obscure and misleading labeling, mistrust of the large corporations who seek to enforce patents on new organisms, a lack of regulatory frameworks, and uncertainty about the technology. How can the future of technology-powered sustainable food be less blurred?

What is CRISPR, and how does it differ from first-generation genetic engineering?

CRISPR-Cas9 — short for clusters of regularly interspaced short palindromic repeats and CRISPR-associated protein 9 — enables rapid editing of the genome. Scientists can quickly alter, add, or remove sections of the DNA sequence.

In an accelerated version of natural breeding techniques, it permits geneticists and medical researchers to modify the genome with accuracy and precision to obtain desirable traits. 

The difference between organisms that have been developed using CRISPR and GMOs is complex, particularly in places that have legislated against the use of GMOs. For example, the EU GMO Directive defines a GMO as "the genetic material of the resulting organisms has been altered in a way that does not occur naturally."

CRISPR can also be used to make cht can also occur naturally. Those organisms would not be defined as GMO as per EU definition. And this is where CRISPR may prove to be of great value.

The first generation of genetically modified crops, or GMOs, were labeled 'Frankenfoods' by critics. When genetic modification of food began in the 1980s, it generally involved taking a gene from one species that had desirable properties and adding it into the genome of another species, the host plant. The hope was the hybrid would be helpful. One supposed example, frost-resistant fish tomatoes, failed in field trials and became a harbinger, according to critics, of everything wrong with genetically modified foods.

Using techniques like CRISPR, next-generation gene-editing promises to be far more precise, faster, and cheaper. Unlike traditional GMO crops, those created by CRISPR technology can be transgene-free; they do not contain DNA from a different species. 

Livneh also points out that mutations that one can change with CRISPR are transformations that could have spontaneously happened in nature at some point in time. 

"The difference is, instead of searching for this specific mutation in nature, we can pinpoint the exact place in the gene that we want to alter. Here, everything that I'm 'changing' in the lettuce already exists in the vegetable but in small amounts," she says. 

A clear solution

The WHO has reported that over 820 million people do not have enough to eat, while two billion suffer from severe food insecurity, and millions of children worldwide suffer from low birth weights and severe vitamin deficiencies. Climate change, undoubtedly, is another hovering issue. Unpredictable weather can broadly impact agriculture.

Here's where GMOs might present themselves as a viable solution.

They could be beneficial in various fields, such as increasing crop yields, producing nutritious foods with more robust tolerance to droughts and flooding, mitigating the catastrophic effects of global warming, and providing greater food yields for the populations that suffer from hunger. While this sounds like what we've been waiting for, others argue that food security is about much more than whether GM foods are safe for the environment. The issues around GMO use are as much about the role of politics, big business, and economics, as about the science.

Writing in response to criticism that Greenpeace cherry-picks data in its opposition to GM crops. "The huge variety of answers to these questions means anyone who thinks the only relevant issue is whether GM crops are safe to eat is by default viewing the existing way society deals with those questions as largely satisfactory," Greenpeace chief scientist Doug Parr wrote in New Scientist.

Others argue that it is the lack of public acceptance, coupled with bureaucratic red tape, which is the real villain and is impeding progress. The resulting controversy, they argue, is discouraging the process of genetically modified foods that could save lives.

To demonstrate, a survey by the Pew Research Center revealed that 57 percent of Americans believe that GM food is unsafe. While half of the adults in the U.S report that they always (25 percent) or sometimes (25 percent) look to see if products are genetically modified when they are food shopping, 31 percent say they never look for such labels, and 17 percent say they do not often look. In addition, several countries have laws banning the use of GM foods.

But, riddled with challenges

According to Barrangou, access to the tool and technology is not limited.

"The ability to use CRISPR to change DNA in plants is very accessible and has been deployed in over 100 countries across the world. The tool is available, the technology is de-risked and well-documented, and the protocols and recipes are out there. But how efficiently can it be deployed? That is a challenge. One must have the right germplasm, the genetic information to know what to edit, the genetic understanding of that crop species, and predictably getting the editing outcome required in commercially relevant elite germplasm -- these are not trivial," he says.

Adding to Barrangou's sentiment, Jennifer Kuzma, the co-director of the Genetic Engineering and Society Center at NC State, tells IE that a gene-edited crop that works in the lab or greenhouse needn't work in the field. "Another challenge is that farmers may not want to buy that particular gene-edited seed if it may not deliver enough benefits directly to them. Crops to mitigate climate change may not fit into their economic models," she says.

A potential risk in biodiversity?

On the dark side, there is the concern that genome-edited crops will create monocultures, which can disrupt ecosystems and pose a risk to biodiversity.

"Industrial farming with a few commodity crops poses a risk to biodiversity. Some of the first generations of traits with genetic engineering exacerbated that risk by making only particular varieties attractive to farmers," says Kuzma. CRISPR too can be used to make only gene-edited crops attractive to industrial farming systems. "However, what we see with CRISPR is that there seems to be a greater diversity of crops that are being worked on. We're not sure if it is a greater risk than first-generation genetic engineering or conventional breeding. But we may have a more diverse portfolio of crops with CRISPR," she explains. 

There is also the potential for off-target edits that may increase certain chemical compounds that might affect non-target species, human health, or nutrition. "Those things are generally monitored for in the regulatory system, but there are a few gaps in that regard. We hope that we set up government systems in place to anticipate them," says Kuzma.

Public transparency and red tape

The regulatory framework, public acceptance, ethical deployment, equity, the commercialization of intellectual properties are major limiting factors that must be addressed, says Barrangaou, and adds, "It is a political, geopolitical, and socio-economic problem."

Regulators, storytellers, narrators, politicians, and PR experts have to responsibly and transparently catch up with science to deploy the technology at scale to benefit customers. "We may be tragically and ironically at a point in time where science is the easy part, which sounds ridiculous. That is the challenge we have before us, and I'm hopeful that the science solutions and the great products that we're able to make today will be embraced the way they should be, by consumers and regulators promptly," Barrangaou says.

Kuzma states that public transparency is imperative. 

"We are at risk of repeating the risk of first-generation GM foods, which was not all that transparent to customers. Many gene-edited crops won't require labeling in the US, only in Europe, unless there is foreign DNA," she says. However, this could mean that there will be less transparency, not more.

Specific segments of the population will always be opposed to genetic engineering depending on value-based positions and concerns around what is natural or not. Though transparency does not always lead to acceptance, it is the goal of developing trust, Kuzma adds.

Where do countries stand on gene-edited food?

Genome-edited plants aren't subject to GMO safety protocols and labeling requirements in the USA and Canada if the genetic alteration 'could' have happened naturally. In 2016, a CRISPR-edited mushroom was allowed to bypass US regulation as it was determined to fall outside the GM legislation by not containing foreign DNA. According to the National Bioengineered Food Disclosure Standard (NBFDS), some products containing GMOs will have to be labeled as bioengineered by 2022. However, it has categorical exemptions that prevent the law from delivering meaningful protections.

In September 2021, the UK government said it would review its approach to GMO regulation "more broadly" so that gene-edited plants are treated differently from GMOs. Countries like Brazil and Argentina also treat genome editing as conventional plants unless they contain foreign DNA.

In December 2020, Japan permitted the sale of a genome-edited tomato. Genome-edited crops must be registered in the country, but they don't need to undergo safety or environmental testing. China recently announced new regulations to pay the way for the approval of genetically modified crops. 

Russia, too has indicated that genome-edited plants that don't involve foreign DNA could be exempt from a 2016 law prohibiting the cultivation of GMOs. 

Since 2001, the EU has placed genome-edited organisms under the GMO Directive. However, the European Commission took a positive stance towards some types of genome editing in a study that suggested legislation could be adapted to make it on par with scientific and technological progress.

The future is CRISPR and more

"CRISPR has the potential for the greater good; however, we should start seeing government regulations not so much as a barrier but as a way to assure the public that they are on the right track to address some of the health and environmental issues that people are going to care about. We need to treat the frameworks and regulations as an asset and not a threat," explains Kuzma. 

Genetic engineers can often engineer around the regulations too. That is an example of how our government systems can keep up with technology, she says. 

The process is ongoing, and revisiting regulatory systems periodically to keep up with the pace of technology is essential. 

But CRISPR is not a one-stop solution.

"Just one technology won't solve the problem. It's an important part of the solution, but it is a pretty complex context. We need more people, resources, and investments to focus on sustainable agriculture and forestry," says Barrangou.

CRISPR is part of the concoction that includes traditional breeding methods, agroecology, and other technologies to deliver greater global food security. With climate change already affecting agriculture and a planet to feed, countries must focus on boosting food security and make regulatory changes that pave the way for more approvals of genetically modified crops. All while creating accountability and transparency.