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Rape/Canola flower and DNA strand

Cibus now claims product of “precision” gene editing was a chance occurrence. Report by Claire Robinson

In a shock turnaround, the pioneer gene editing company Cibus is claiming that its flagship product, sulfonylurea herbicide-tolerant canola (SU Canola), isn’t gene-edited after all but is the result of an accident in a laboratory petri dish.

However, a scientist who helped develop a new testing method for the crop has dismissed the likelihood that the canola was developed through random chance rather than gene editing as being "vanishingly small”.

What’s surprising about Cibus's claim is that the company has been saying for years that its herbicide-tolerant canola (oilseed rape) was made with “precision gene editing”. In fact, the gene editing technique that Cibus used, known as oligo-directed mutagenesis (ODM), constitutes the very foundation of its business model.

What caused Cibus’s U-turn? The answer may lie in the timing: the company only made a public statement about the claimed absence of gene editing immediately after the SU Canola became detectable. Earlier this month a scientific paper was published, reporting the development of the first-ever publicly available detection method for the gene-edited herbicide-tolerant SU Canola, which is marketed under the brand name Falco.[1]

Gene-edited plants are GMOs and fall within the scope of EU GMO law, according to a European Court of Justice ruling of 2018. Environmental and consumer groups based in the EU have long been concerned that Cibus’s herbicide-tolerant canola, which is grown in the US and Canada but is not authorised in the EU, was being illegally imported. When EU officials discussed the European Court of Justice ruling with the Commission, some government officials said they were “not able to fulfil all their obligations to carry out controls” due to the lack of a detection test.

Research is “game-changer"

The new research, funded by a coalition of NGOs and organic, natural, and non-GMO food-related associations, showed that provided information is available about the genetic changes made, a gene-edited crop can be uniquely identified using standard GMO detection technology, even if the intended DNA change is no more than a point mutation (i.e. a change of a single base pair/nucleotide).

What the test cannot do is detect the technique by which a mutation was brought about – but under EU law it doesn’t need to.[2] The way that the law deals with proof of origin for all GMOs – products of gene editing included – is to require the developer to declare that their product is a GMO and provide a test method and reference material. The crucial value of the new detection test is that it means that EU countries can now test canola imports to see if Cibus’s unauthorized GMO is present.

According to Greenpeace, which helped fund the research, the new detection method is a “game changer” in at least two ways: “Firstly, it achieves what many have said is impossible – being able to distinguish a gene-edited crop from similar crops that are conventionally bred or engineered using established GM techniques. Secondly, it enables regulators and companies to test for Cibus’ gene-edited canola, which they were previously unable to.”

Random mutation?

Now that such a test is available, Cibus faces a situation in which ships carrying cargoes of canola contaminated with its gene-edited canola could be turned back at Europe’s ports, disrupting all Canadian canola exports to the region and destroying the European market for Canadian canola growers.

Perhaps this explains why Tony Moran, Cibus's vice president of international development, responded to reports of the new test by telling Politico that the company’s canola varieties sold in the US and Canada are “not gene-edited”. Moran added that the mutation in the crops that confers herbicide tolerance “occurred spontaneously in cell culture and that's not unusual”.[3]

Cibus made the same claim to the seed industry association Euroseeds, which said, “the varieties were in fact developed from spontaneous somaclonal variation”. Euroseeds concluded on the new study, “The publication provides a method to detect a single point mutation originating from a non-GM mutagenesis method” (our emphasis).

Oddly enough, Cibus has not gone public with any statement on its website or social media, apparently preferring to give out its message via a defensive quote to the media and an industry association. Such behaviour could imply that, far from being confident in the safety and legality of its product, it has something to hide. It’s also possible that Cibus doesn’t want people to know that their proprietary “precision” gene-editing technology has (according to Cibus’s narrative that the crop is not gene-edited) failed to deliver the intended outcome.

Misleading investors?

Let’s assume for a moment, for the sake of argument, that Cibus’s claims about the canola being a product of random mutation are true. This would raise serious questions about whether it has misled investors. Cibus has long promoted its herbicide-tolerant canola to the business press as a triumph of gene-editing. For example, in 2018 the biotech economy news outlet Xconomy reported that “Cibus’s first commercial product is SU Canola, a variety of canola that is tolerant to sulfonylurea, a type of herbicide. The company achieved this herbicide tolerance with its proprietary Rapid Trait Development System (RTDS) technology, which edits genes without introducing foreign DNA.”

Xconomy also reported that “Sales of Cibus’ first product, a gene-edited canola, have gone so well that the San Diego company has raised $70 million in new financing to boost its commercialization efforts.”

How do the investors feel about giving millions of dollars towards developing a “precision” gene-editing technology that, according to Cibus’s new claims, has failed to deliver even one genetically simple trait: that of herbicide tolerance? And how do they feel about being misled over a period of years?

There’s little chance, by the way, that Xconomy misreported the story, since Cibus prominently links to it in the “In the news” section of its website.

Regulatory documents confirm ODM gene editing was used

What did Cibus really know and believe about the origins of its herbicide-tolerant canola? The most reliable source should be the documents that Cibus has submitted to regulators. Based on Cibus’s submissions, Health Canada stated that Cibus used ODM  (gene-editing) to develop SU Canola derived from the GM transformation "event" number 5715, and the Canadian Food Inspection Agency said the same thing.

Both agencies noted that Cibus thought (Health Canada used the word “hypothesized”) that the intended genetic change could be the result of “spontaneous somaclonal variation”. But neither the company nor the agencies made any firm determination that it was.

In 2014 Cibus corresponded with the BVL – German Federal Office of Consumer Protection and Food Safety – in an effort to determine whether its SU Canola, and specifically canola line BnALS-57, the parent of 5715, fell under the EU’s GMO laws or not. Cibus wrote, “The majority of the mutations in the collection [of canola lines with mutations in a specific gene that can influence tolerance to herbicides] are the direct result of RTDS GRON targeted mutagenesis [ODM gene editing] experiments.”

In short, Cibus seems to imply that the herbicide-tolerant trait was highly likely to have resulted from the ODM gene editing.

Little wonder that Greenpeace concluded from the company’s various statements that Cibus appears to be deliberately engaging in a “confusion game”.

Greenpeace’s Franziska Achterberg said of Cibus’s turnaround, “Cibus cannot have it both ways – telling North American regulators, growers and investors that its products are made using gene editing, and telling EU regulators that they’re not. They need to own up to the fact that they have used ODM in the process of making their canola. ODM is a technique that falls under EU GMO law, therefore their canola is subject to EU GMO law.”

Indeed, the relevant entries in the Euginius database of GMOs and the Convention on Biological Diversity’s Biosafety Clearinghouse confirm 5715’s status as a GMO.

Regulatory agency chicanery

At least two regulatory agencies appear to be assisting Cibus in its “confusion game”.

The first is the Canadian Food Inspection Agency. Up until July 2020, all versions of Cibus’s registration document for 5715 canola stated of its parent line BnALS-57, “Although BnALS-57 was isolated following treatment of cells with the RTDS, the mutation in BnALS-57 is thought to have been created as a result of a spontaneous somaclonal variation that occurred during the tissue culture process, rather than due to the oligonucleotide used in the RTDS.”

This is the link to the version of April 2015. This is the link to the version of September 2017. 

However, the reference to RTDS was removed in July 2020. This is the link to the current version. The fact that the registration document was modified in July is stated at the bottom of the page: “Date modified: 2020-07-10”.

It seems extraordinary that a regulator would change an official document without explanation or scientific justification. One possible reason could be to protect Cibus from the consequences of any discovery of illegal 5715 canola in EU imports. Another could be new knowledge on the part of the agency that the “precision” gene-editing technology of ODM didn’t actually work and that the herbicide tolerance is a product of a random mutation.

The second agency that has weighed in with support for Cibus is the German Federal Office of Consumer Protection and Food Safety, BVL. BVL has issued a statement (Google translation is here) saying the mutation in the Cibus canola lines that confers herbicide tolerance “was not created by genome editing methods”. It reports the updated Canadian Food Inspection Agency document as saying, “it was the result of a spontaneous mutation (somaclonal variation) that occurred during the tissue culture process and not a result of the ODM technique”.

What’s fascinating about BVL’s statement is that what was said by Cibus to the Canadian authorities only in terms of a hypothesis (the mutation could have been the result of spontaneous mutation) has been converted into a flat statement of fact by the German agency (it was the result of spontaneous mutation). Yet BVL provides no evidence or scientific argument to back up its views.

While BVL’s name suggests it is in the business of protection of the consumer, its actions suggest its priority is the protection of the GMO industry.

Scientists comment

According to Dr John Fagan, senior author of the paper reporting the development of the detection method, the likelihood that the mutation conferring herbicide tolerance “was generated by random mutation due to somaclonal variation and not due to ODM is vanishingly small”.

Dr Fagan added, “In light of this probability, it is highly preposterous that a company that has invested tens of millions in developing a particular method of gene editing would turn around and claim that its first commercial product made using this gene-editing method was not actually the result of that method but happened accidentally via random mutagenesis.”

Dr Michael Antoniou, a London-based molecular geneticist who was not involved in the research, said, “Ultimately, whether the single DNA base change that resulted in the generation of SU Canola was a product of RTDS or tissue culture-induced, random somaclonal variation is irrelevant with respect to the detection method developed by Dr Fagan and colleagues. This is because the method they have developed reliably detects a single DNA base unit change, regardless of how it came about. Thus the method described is above reproach and should be adopted by Europe's detection laboratories to screen for the presence of unapproved GM or gene-edited crops in the human and animal food chain.” 

Quibbling won’t save Cibus

According to GMWatch’s interpretation, it is also irrelevant under the EU’s GMO laws if a specific mutation was generated spontaneously by tissue culture or via the gene editing genetic modification process. Under this interpretation, if genetic modification techniques have been used to develop a crop, it is a GMO, even if the specific trait that the genetic engineers are aiming to achieve occurs via spontaneous mutation.

In this regard it’s noteworthy that the BVL has not removed SU Canola from the Euginius GMO database, which it runs in collaboration with Wageningen University and Research.

So as far as we are concerned, Cibus’s SU Canola is a GMO. The inevitable conclusion is that the presence of this canola in EU imports is illegal and must be screened for using the new test.


Notes

1. The varieties offered in the US are called 68K, 32K and 40K. A different set of varieties offered in Canada. 5715 is the name of the transformation event registered in Canada and in the EUGinius and UN CBD Clearinghouse databases. Some of the varieties are based on this event and others on a retransformation event called 5720, also registered in Canada. At least two of the lines sold in the US and Canada, 40K and 68K, are derived from GM transformation event 5715. A third line, 79K, is derived from a retransformation of that event called 5720, which Health Canada cleared in April 2019
2. GMO advocates in Europe (e.g. Euroseeds) have wrongly implied that a GMO testing method must be able to prove how the GMO was made. However, there is no such requirement in the EU’s GMO laws. 
3. Arthur Neslen, EU countries may have a way to find gene-edited crops in imports. Politico, 7 Sept 2020 (paywalled).