Gene editing

GENE-EDITING TECHNOLOGY has the potential to revolutionize crop and animal development globally. For Canadian researchers, however, the federal government’s ambiguous and slow-moving regulatory system is preventing new agricultural products from reaching farmers and consumers alike.

This problem was expressed by speakers and attendees at a meeting hosted by Ontario Agri-Food Technologies and CropLife Canada in Toronto earlier this spring. The meeting provided a forum where biotechnology experts discussed how Canada’s regulatory system could change to allow more efficient commercialization of gene-edited plant products.

Emerging from those discussions was one central theme — the government still needs to clearly define what is required to develop and market a gene-edited organism.

WHAT IT TAKES TO MARKET A NEW PLANT VARIETY

Ian Affleck, vice-president of plant biotechnology with CropLife Canada and one of the meeting’s speakers, says Canada’s current regulatory system was developed in the early 1990s when the government was trying to figure out how to regulate GMOs.

At that time, the decision was made to regulate based on a product’s novelty rather than the process used to develop it (the term “plant with novel trait,” or PNT, is often used). To ensure regulatory consistency, though, all methods of plant breeding had to be included in scope. This continues to raise debate on what is considered a novel trait, and what is not.

While rigorous, Affleck and many other meeting attendees reiterated the significant expense such a system imposes on companies developing what might be considered PNTs. For CropLife’s members, Affleck says it can take up to $150 million and 13 years for a PNT to go from development to commercialization.

WHAT IS GENE-EDITING & WHERE DOES IT FIT?

Gene-edited plants and animals have had DNA added, removed, or somehow altered to achieve a specific outcome (e.g. disease resistance, higher yield, etc.). This is done using only the organism’s existing DNA and without the addition of genetic material from unrelated species — as is the case with more traditional transgenic (aka GMO) crops such as Bt Corn. CRISPR is perhaps the most widely recognized example of a gene editing technology.

According to Stuart Smyth, genomics expert and associate professor with the University of Saskatchewan’s Department of Agricultural and Resource Economics, Canada has yet to conclusively decide whether or not the term gene-editing automatically means the plant has a novel trait. This means plant breeders have no idea how long it will take to commercialize new varieties, nor how expensive it will be.

For example, a gene-edited herbicide-tolerant canola variety, called SU Canola, was successfully commercialized in 2018. Despite its herbicide tolerance — something considered a novel trait in transgenic crops — the government did not push back against it being marketed as a non-GMO variety. This, says Smyth, seems to indicate the government does not consider gene-edited crops to be PNTs.

Conversely, Affleck says the case of waxy corn is less solid.

Waxy corn is a maize type with a different starch profile. This trait, he says, has been around since the 1930s and is thus not novel. Therefore waxy-corn developed via gene-editing does not appear to require pre-commercialization safety assessments in Brazil, Argentina, Colombia, Chile, Israel, and likely Japan. Despite this, the Canadian Food Inspection Agency (CFIA) and Health Canada have yet to specify whether gene-edited waxy corn is or is not novel — despite being directly asked over 18 months previously (as of March 2019).

COSTS A MAJOR BARRIER TO SMALL COMPANIES

Speaking after the event, Trevor Charles, professor of microbiology at the University of Waterloo and director of the Waterloo Centre for Microbial Research, says forcing developers to play this commercialization guessing-game really limits the chance for small companies and start-ups to succeed — at least domestically. Even bringing non-gene-edited strains to market takes a very long time in Canada.

Charles is also the chief strategy officer as well as co-founder of Metagenom Bio — a small Waterloo-based company developing genomics and microbiome products for use in agriculture and wider environmental applications. This includes bacteria and fungi that can help legume crops fix nitrogen, influence plant stress responses, or stave-off pathogens with specific antimicrobial properties.

In the United States, for example, his company has to fill out a form, pay a $50 or $100 fee, and can begin marketing the product in question almost immediately — and in some states even this isn’t necessary.

But Canada is a completely different story.

Regarding a recent product developed by his company, Charles says it took nearly one year and $100,000 to gather all the required information just to apply to the CFIA — the body which reviews new crops alongside Health Canada. CFIA will then hold it for two years. During this time, he and his colleagues have no idea whether the product will even be accepted. This, he says, is no incentive to invest in market development.

“As a Canadian company I think it’s a big problem that we have to rely on other jurisdictions to get ourselves off the ground […] A lot of companies are under the assumption there are huge problems,” he says.

He adds agricultural products like those previously mentioned already exist to a degree, but nearly all have been developed by isolating useful wild strains of bacteria and fungi. Indeed, he says there are virtually no gene-edited versions of such agricultural products available, despite the fact that researchers like himself have had the technology at their fingertips for some considerable time.

INDUSTRY MAKES RECOMMENDATIONS

Efforts to determine how the regulatory system can be clarified are ongoing. As part of a joint industry-government working group — operating under Agriculture and Agri-Food Canada’s current Grains Roundtable – Affleck says four recommendations have been proposed:
• Create one overarching regulations document that is readily accessible (currently no such document exists, and searchers must consult multiple, often not mutually-supportive sources).
• Modernize information requirements, such as rationales for exemptions and tiered assessments.
• Improve support (on the government side) for innovators.
• Communicate the new approach to other jurisdictions (in an effort to once again position Canada as a proactive global leader in biotechnology regulation).

For Charles’ part, identifying specific criteria — and reducing the amount of time developers must wait to market a product that meets that criteria — are the most significant opportunities.

“It’s not waiting two years to find out whether you can sell or not,” he says.

WORLD-WIDE REGULATIONS

According to Stuart Smyth, genomics expert and associate professor with the University of Saskatchewan’s Department of Agricultural and Resource Economics, countries like Argentina, Brazil, and the U.S consider gene-edited plants to be separate from GMOs as long as no foreign DNA is present. By consequence, this also means commercialization takes less time and does not incur the same high regulatory cost as PNTs, though nuances between these and other countries — many of which are key Canadian commodity competitors — do exist.

The European Union, by contrast, took another course. In July 2018, the EU Court of Justice ruled mutagenic genome-editing technologies must be regulated as equivalent to GMOs, regardless of whether foreign genes is or is not present in a plant. This happened despite some EU countries, specifically Sweden, pushing for policies more reflective of the U.S.

Notably, says Smyth, the decision to regulate any genetically edited crops as GMOs has led to a mass exodus of innovation dollars from Europe. Over the past 20 years, the EU has gone from receiving one-third of global agricultural research and development investments to just under 10 per cent.

Where those research dollars will go, he adds, depends in part on how efficient and effective a country’s regulatory system is. •