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Gene editing: what can it deliver for agriculture?

Gene editing can potentially offer plant and animal breeders endless opportunities to optimise food production, but whether its benefits can deliver on a global scale will depend on how regulators view the technology.

Gene editing is a powerful tool for global agriculture, offering breeders the potential to wipe out genetic disease, improve drought resistance, boost nutrient efficiency, and prolong shelf life.

The approach involves making a cut in the plant’s DNA using molecular scissors, then the changes to the sequence are made by the plant’s own repair process. It enables breeders to insert, delete or replace genetic traits within the organism’s genome.

There are several approaches, but the main method is called CRISPR-cas9, which has taken the scientific community by storm. However, questions have been raised over who will determine the technology’s future and how.

In the EU, the big question is how CRISPR-Cas9 will be regulated. If the products it produces are deemed genetically modified organisms (GMOs), and, therefore, banned from use, the EU’s agricultural sector could miss out on their benefits while other countries reap their rewards.

Potential in agriculture

To understand how the EU regulates genetic engineering, you first need to understand how CRISPR-Cas9 works. Simply, it enables scientists to quickly and easily edit the DNA of any living species and is based on a natural process where bacteria protect themselves from viruses.

EU flags outside the European Commission, Brussels, Belgium - 06 Jun 2017. Photo credit: Shutterstock

Gene editing will be discussed during a conference hosted by the European Commission. The conference, Modern Biotechnologies in Agriculture: Paving the way for responsible innovation, will take place in Brussels on 28 September. Photo credit: Shutterstock

By comparison, cisgenesis is a GM process whereby genes are artificially transferred between organisms that can be otherwise conventionally bred. Transgenesis, on the other hand, introduces genes from outside the plant or animal’s genome.

By far, gene editing is easier to use, and less expensive than both cisgenesis and transgenesis. More importantly, it’s more precise.

Regulation

All breeding technology is subject to regulation, which differs from country to country. In Europe, there is much discussion on whether or not gene editing and cisgenesis should fall under the same regulatory process as products produced by transgenesis.

The EU Commission defines a GMO as “an organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination.”

During a talk at the European Potato Trade Association (EuroPatat) conference, held in Antwerp earlier this year, René Custers of the Flemish Institute for Biotechnology (VIB) in Belgium spoke about the ambiguity of this definition.

Powdery mildew Erysiphe graminis pustules on a wheat leaf. Photo credit: Alamy Stock Photo

Scientists in China have used gene editing technique CRISPR to produce a wheat variety resistant to powdery mildew. Photo credit: Alamy

“My interpretation, then, is a number of these precision technologies will not lead to organisms that are covered by the legislation,” he said. “That’s merely a legal thing. Another question, of course, is whether or not certain organisms should be under regulatory oversight.”

In conventional breeding, products with small genetic alterations are produced all the time. Following that, they are tested and put on the market as new varieties.

“That process has, in general, led to the introduction of crops that are safe,” said Mr Custers. “In the old days, of course, that was a very blind approach. People were just breeding without actually really knowing what the cause of a certain characteristic was.”

“Today, we know much more about what is happening on the genetic level, and we have much more insight; if we select for a certain characteristic then we know what the actual cause of that characteristic is, and we can make an estimation on whether that will lead to something that is safe or not,” he said.

Guidance document

According to Mr Custers, the European Commission has been looking at gene editing for a number of years already. A working group was working on a report, he said, which they had promised to publish as a guidance document on how to integrate these new technologies into the current legislation.

After several postponements, the report has still not been delivered, and it is Mr Custers’ personal opinion that it will not be published. Even if the paper was published, there are no guarantees it would be accepted, said Mr Custers at the conference.

“It could be challenged by anybody who would like to, and then go to the European court,” he said, pointing out that France had already initiated the process. Meanwhile, the commission has been working with its scientific advisers to produce an explanatory note on agricultural breeding technologies.

The potential of gene editing isn't confined to crops, with the technology able to produce pigs immune to a damaging virus. Photo credit: Alamy

The potential of gene editing isn’t confined to crops, with the technology able to produce pigs immune to a damaging virus. Photo credit: Alamy

The document will also form the basis of an important conference organised by the commission at the end of September on modern breeding technologies in agriculture.

“If you look at the precision breeding technologies and the way we deal with small alterations in traditional breeding, then I would say that there is not very good argumentation to state that we need very strict oversight for these new products,” Mr Custers said.

US situation on gene editing

Meanwhile, in the US, regulatory bodies maintain a product-focused, science-based regulatory policy.

Genetically engineered crops and the food derived from them, says Jason Dietz, policy analyst in the Center for Food Safety and Nutrition, are regulated by the Food and Drug Administration (FDA) in cooperation with the US Department of Agriculture (USDA) and the Environmental Protection Agency (EPA).

“Food growers, manufacturers, and distributors are responsible for taking the steps necessary to ensure that their food products marketed in the US are safe and lawful, regardless of the process used to produce the food,” he says.

Legislation around animals and foods derived from genetically engineered animals is a little different, though.

Laura Epstein, senior policy adviser in the Center for Veterinary Medicine, explains: “The draft guidance clarifies that intentionally altered genomic DNA meets the definition of a new animal drug, unless otherwise excluded, because it is intended to affect the structure or function of the animal,” she says.

Gene editing

  • Gene editing uses “molecular scissors” to insert, delete or replace DNA in an organism’s genome in a very targeted way.
  • There are a number of gene editing techniques, but the latest pair of scissors available to gene-editing scientists is CRISPR (pronounced “crisper”) and was awarded the Science Magazine 2015 Breakthrough of the Year.
  • A specifically designed mechanism recognises the piece of DNA to be cut and guides the molecular scissors to its location on the organism’s DNA sequence. Once snipped, the DNA tries to repair itself and inserts a genetic “stop signal”, knocking out the function of an undesirable trait.
  • Examples of gene-edited crops already on the market in the US include a browning-resistant button mushroom, an improved storage potato and a waxy maize variety that produces a higher starch content for processors.

Earlier this year, the FDA initiated a public dialogue on specific questions related to genome editing applications in animals and in plant-derived foods. The FDA is considering the input it received. “The FDA is committed to fulfilling its mission to safeguard public health, while encouraging innovation and competitiveness,” says USDA media spokesperson Anne Norris.

“The agency maintains a product-focused, science-based regulatory policy, in accordance with specific legal standards applicable to each type of product.” “The FDA also supports regulatory science activities that help develop scientific tools, standards, or other information that can inform regulatory decision making,” she adds. “The FDA’s focus is on ensuring safe and responsible development and use of genome editing applications.

CRISPR’s potential is seemingly endless

For Geert de Jaeger, leader of the functional interactomics group at the Department of Plant Systems Biology at Ghent University, CRISPR technology is highly important to plant biologists.

“The main advantage of CRISPR, as compared with former genetic engineering tools, is that it allows researchers to change the sequence of specific genes in a targeted way,” he says. “This has been so far quite difficult in plants.” Prof De Jaeger and his colleagues are using the technology to knock out genes in thale cress and corn.

“But in the near future we are optimistic that we will use CRISPR to boost the activity of a group of genes simultaneously, to insert new genes in a site-specific manner, or even to replace genes in plants,” he said. “These are applications that have been so far impossible or very tedious and difficult in plants.”

Already, CRISPR technology has been used in China to create a strain of wheat resistant to powdery mildew. In collaboration with DuPont, California-based Caribou Biosciences, is working to create drought-resistant corn and wheat strains.

And it isn’t just plants. Using gene-editing technology, UK-based scientists have produced pigs that are protected from porcine reproductive and respiratory syndrome, a virus that costs the pork industry billions every year. In the US, a company called Recombinetics is producing hornless dairy cattle using genes from smooth-headed beef cattle.

Better beef

In addition, using a naturally occurring gene variant in beef cattle results in a 7-10% increase in muscle mass. The company says the genetics produce more tender meat for consumers and increased carcass yield for producers.

Other firms are developing chickens that only produce female offspring, and beef cattle that only produce males. A San Diego-based company has produced herbicide-resistant oilseed rape. In potatoes, Calyx, a company in the US, is developing late blight resistant potatoes using CRISPR technology. At the moment, work is in its early stages but the research shows great potential.

The potential applications are seemingly endless, which makes the regulation of these products crucial to EU farmers. Will they be able to use these advanced tools? Or will the regulatory bodies ban them altogether? Mr Custers thinks it’s especially important that precision-breeding technologies remain available to all breeders.

“If you were to regulate them in a very strict way, as you do with GM, then you push those technologies into the hands of the happy few, namely the very big companies,” he says. “And the smaller ones will not be able to make use of the benefits that these new technologies offer.”

These questions and more will be discussed during a conference hosted by the European Commission. The conference, Modern Biotechnologies in Agriculture: Paving the way for responsible innovation, will take place in Brussels on 28 September.