RNA interference disrupts cellular signals and is highly species specific, allowing for insecticide sprays or built-in defence traits to protect against only the target insects or diseases. Flea beetle sprays, for example, would not do anything to non-target beneficials.
Gene-editing tools such as CRISPR and Cibus’s GRON system are highly targeted and can be used to tweak already high-performing hybrids, adding new traits for specific end-use qualities, protection from new disease pathotypes or better weather tolerance. “And instead of taking 10 years to develop a commercial-ready line with a brand new trait, with gene editing it might only take two years,” says Krista Thomas, director of plant innovation with the Canada Grains Council (CGC).
“Because gene editing can bring a lot of new traits to market and so much faster than current technology, it can put canola in an extremely competitive situation and help Canada’s canola industry achieve its goals.”
David Sippell, Cibus vice president and North America general manager for canola, agrees that the speed of development is a key factor. “Because gene editing can bring a lot of new traits to market and so much faster than current technology, it can put canola in an extremely competitive situation and help Canada’s canola industry achieve its goals,” he says.
Gene editing and RNA interference can improve agriculture’s ability to protect bees from off-target sprays, enhance productivity in the face of challenging pests and keep pace with consumer demand for protein, to give just a few examples.
Given all this potential benefit, where are we with regulations?
Gene editing: The tool and the regulations
CRISPR, probably the best-known of the gene-editing tools, was adapted from a genome-editing system that bacteria naturally use to attack viruses. CRISPR uses an enzyme (Cas9 is the most common) to cut DNA at a target location. The enzyme can also bring with it genetic instructions to change, add or remove genetic material, allowing researchers to customize a new trait, relying on a cell’s natural DNA-repair system to complete the job. With these tools, seed companies can quickly add a new trait to their existing top-performing varieties without the need to work the trait up to commercial lines through years of crossing and back-crossing.
Cibus uses another gene-editing technique that employs a gene-repair oligonucleotide (GRON) to work with the plant DNA’s natural repair system to make very targeted improvements to genetic code.
Sippell hopes that this summer the company can field-test a new shatter-tolerant canola, developed using its gene-editing techniques. These trials will produce data needed for the registration process. Also well underway from Cibus are a new disease-resistance and high-oleic specialty oil traits. “It will be a little different from other high oleic oils on the market, but we’ll be sharing those details later,” he says.
Gene editing has brought other new companies into plant genetics. Saturn AgriSciences, based in Guelph, Ontario, is a new subsidiary of U.S. company Benson Hill Biosystems. In partnership with scientists at the University of Guelph, Saturn is looking at gene editing to “turn off genes that are anti-yield,” says Mohammed Oufattole, vice president of research and development at Benson Hill. Additionally, the Guelph team has developed the know-how to improve photosynthesis efficiency in crops and is gearing up to deploy its technology in canola using gene editing.
Oufattole says the relatively low-cost of getting commercial results using gene-editing tools can bring smaller companies into the innovation space, as long as regulations are science-based and not too burdensome on innovation. “If regulations are too expensive, innovation will keep consolidating among the big corporations,” he says.
Regulatory steps to bring gene-edited varieties to market have not been tested so no one is clear yet on how it will go.
“What we need now is a more predictable system, based on risk, where all the steps are clear. Some of Canada’s trading partners are providing a much better regulatory climate for crop innovation.”
“The regulatory system we have now is the same one we had 20 years ago. It’s case-by-case,” says Thomas with the CGC. “What we need now is a more predictable system, based on risk, where all the steps are clear. Some of Canada’s trading partners are providing a much better regulatory climate for crop innovation.”
The United States Department of Agriculture (USDA) provided some clarity in March 2018 when it announced it has no plans to regulate plants that could otherwise have been developed through traditional breeding techniques – as long as they are not plant pests. In addition, the USDA has a process called ‘Am I Regulated?’ where developers can query the agency as to whether their latest genome edited product is a regulated article. While this is a step forward for innovation, Thomas says the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) – who also have authority in this space – continue to evaluate their regulatory approaches.
Japan is also pulling further ahead, she says, with public consultations this spring on its gene-editing regulations. China is doing a lot of research and development on CRISPR in crops, but the domestic seed industry wants to see clear rules, Thomas says, adding, “We are eager to see what China’s approach will be because it could have a major impact on trade.”
In Canada, gene-edited plants can fall under ‘novel products’ regulations, which are the domain of the Canadian Food Inspection Agency (CFIA) and Health Canada. The CFIA looks at the environmental and feed safety of the plant, and approves it for sale as seed or animal feed. Health Canada covers food safety.
“We believe,” Sippell says, “that given the precise nature of the changes that these tools allow, they will be perceived favourably by the regulators.”
RNA interference: The tool and the regulations
An explanation of RNA interference starts with deoxyribonucleic acid (DNA), the long double-helix molecules repeated in all cells. DNA contains the genetic codes for growth and function of an organism. Ribonucleic acid (RNA) picks up those codes and sends code-containing messages throughout the organism to grow, defend, set seed, senesce, and everything else a plant does. DNA is the instruction book, RNA is the foreman carrying out the instructions. RNA interference (RNAi) is as it sounds: Researchers have found out how to use strands of RNA code to interfere with these critical messages. To give a Canadian canola example, Mark Belmonte and his colleagues at the University of Manitoba have found an RNAi-targeted gene within the sclerotinia pathogen that controls a function necessary for its survival. With that discovery, they then made an RNAi molecular fungicide that stops that function and kills the fungus.
There are two choices to deploy such an RNAi discovery. One, the RNAi molecule can be made into a foliar spray. Two, a plant could be given a gene to produce the defence molecule itself.
No RNAi pesticide sprays have been approved in Canada or any of our major markets. Bayer has a product in development to treat for varroa mites in honeybee hives. Honeybees actually carry the product into brood cells within their hives where the mites initially infest bees, with the product having no effect on the bees. Kristin Huizinga, who leads RNAi regulatory efforts for Bayer in St. Louis, Missouri, expects the company to make a submission to the U.S. EPA sometime this year and then to the Pest Management Regulatory Agency (PMRA) in Canada in the following years.
“We see this as a biological pesticide, but there hasn’t been another RNAi pesticide of this type to advance through the regulatory process,” Huizinga says. “In general, the first product in a category receives lots of scrutiny just by nature of being the first – and that means the approval process may take longer.”
Even before making an official submission for approval, a new product needs to go through a series of tests, including mammalian toxicity and ecological toxicity on non-target organisms. Companies must also provide details on how a product is made and how it will be used.
“We are in close communication with the EPA throughout the process,” Huizinga says.
Close communication with regulators is important, says André Gagnon, media relations officer for Health Canada. PMRA requires a similar set of studies, and Gagnon says the first step in bringing a pesticide to market in Canada is to request a pre-submission consultation with PMRA. “In general, a pre-submission consultation will provide guidance on how to submit a complete, high-quality application package to register a pest control product or to amend the registration of a registered pest control product,” Gagnon says. It also sets application timelines and outlines the required forms and data requirements.
“Currently, there are no open applications to register RNAi pesticides in Canada,” Gagnon says, but adds: “In 2017 and 2018, PMRA received several research applications for RNAi pesticides for use under specific conditions (including a restriction on the size of the area treated and the requirement that the crop be destroyed at the end of the trial), most of which were approved.”
The potential for RNAi has brought some new names into the space. GreenLight Biosciences, for one, developed a new way of scaling up RNAi products for commercial use and, seeing the potential in agriculture, has hired some agricultural expertise. Mick Messman, GreenLight’s chief commercial officer, says they’re furthest along with a Colorado potato beetle protection product. The company also has a potential RNAi flea beetle product in the discovery phase.
Farther along the flea beetle pathway is Syngenta, which is actively researching the use of RNA-based biocontrols as a foliar spray for flea beetle control. “We have demonstrated that this platform is effective as a control agent and we are focused on field trials to understand this activity in production agriculture settings,” says Chris Davison with Syngenta Canada.
“It is difficult to anticipate exactly when a new RNA-based biocontrol product will come to market, especially when they are in active research mode, but we expect it will be several years yet,” Davison says. “We continue to work with regulators around the world regarding the regulatory pathway and what is required as part of the development process.”
Market acceptance key
No matter what we approve in Canada, whether a gene-edited variety or an RNAi pesticide, the Canola Council of Canada will not support the use of seed innovation or pesticides that would cause concerns in our major markets.
“We have a strong record of partnership in the canola industry. Our value chain, which brings growers, life science companies, processors and exporters together, continues to have a strong commitment to encouraging innovation while ensuring stable access to export markets.”
“We have a strong record of partnership in the canola industry,” says Brian Innes, vice president of public affairs with the Canola Council. “Our value chain, which brings growers, life science companies, processors and exporters together, continues to have a strong commitment to encouraging innovation while ensuring stable access to export markets.”
Sometimes this means that beneficial seeds or pesticides can’t be commercialized in Canada because they are not accepted in export markets, Innes says.
With significant uncertainty around how large canola markets will regulate new plant breeding tools, how these policies are finalized is of significant interest to the canola industry. That’s why the Canola Council is a member and significant funder of the Canada Grains Council’s work to advance trade promoting plant breeding policies internationally. With policy issues affecting grains being similar across commodities, the Grains Council takes the lead on national and international advocacy related to plant breeding for all grains.
When it comes to innovation in canola, the Canola Council is responsible for ensuring coordination among the canola value chain and advocating for canola innovation. By promoting transparency and bringing the weight of the full value chain to advocacy efforts, the Canola Council works for the long-term success of all members of the canola value chain.
While agriculture works through these regulations and eventually brings these new tools to the fields, Sippell anticipates a positive outcome. “This is a good news story around innovation for canola in Canada.”