The precision problem in genome editing

August 2021

In 2018, the European Court of Justice gave its opinion on EU law with regard to gene editing. It concluded that techniques which use lab-made nucleic acids (such as DNA or the related RNA) to alter genetic material in a way that does not occur naturally are GM and are, therefore, subject to GMO regulation [1].

The most popular and most studied gene editing technique due to its versatility, simplicity, speed and low cost is 'CRISPR' [2]. CRISPR is intended to make precise changes by cutting the DNA at precise locations in the genome; after this, natural cell repair mechanisms take over and stick the DNA back together again. The re-assembled DNA may incorporate either random or directed changes.

This Court Opinion did not, of course, suit the biotech industry nor all the research institutions and scientists whose work is focused on GM, and who maintain that "the benefits are so clear that furnishing reliable scientific evidence is unnecessary" (see Gelinsky and Hillbeck). Nor did it suit the European Commission, heavily lobbied as it is by the agricultural, agrichemical and biotech industries.

Meanwhile, in the UK, questions put to the Department of Environment Food and Rural Affairs (DEFRA) in preparation for Brexit revealed some very vocal Lords and Baronesses with declared interests in farming and in Rothamsted Research (a major centre for GM crop development in the UK).

The Parliamentary Under-Secretary of State for DEFRA informed the Lords that "we did not agree with the 2018 European Court of Justice ruling that all GE (gene edited) crops must be regulated as GMOs". The basis of this disagreement seems to be that gene editing "merely escalates a natural process". He assured them that "we rely on the best science and have a science-based approach."

One Viscount claimed "there is not even a theoretical possibility that a genome-edited plant is less safe than a conventionally bred variety with the same trait".

There seems to be a suggestion that the European Court of Justice didn't use science to reach its conclusion (indeed, elsewhere, the Court was even accused of using 'pseudo science'). So, what does a 'science-based approach' actually tell us about the safety of gene editing?

A review of genome editing safety published in 2019 found that the current level of knowledge and experience to address the issue is "insufficient".

The source of this insufficiency seems to lie in the pro-GM mindset: to biotech scientists 'safety' is an inherent attribute of the 'precision' in gene editing. This is a questionable assumption because science is finding that gene editing is peppered with surprises. Science has reported, for example:

1. Widespread secondary mutations in areas of the genome not targeted by the gene editor [3]
2. Mutations within non-target DNA whose sequence approximates the gene editor's homing mechanism [4]
3. 'Eliminating' a gene by disrupting it with a gene editor actually just creates a new gene [5,6]
4. A 'surprising' diversity of edits arising at the target DNA site itself [7]
5. Multiple head-to-tail insertions of the desired new section of DNA (Skryabin)
6. In plants, successive waves of small unpredictable mutations arise at each stage of the creation of a gene-edited plant [8]
7. In animals, DNA (possibly from other species) can be captured from the cell's environment and incorporated during the editing procedure (Ono).
8. And then there was the gene editing 'therapy' trial in which two out of the eleven children developed leukaemia, and the gene edited hornless cattle with multiple extra marker genes [9], and the gene edited cassava which recreated mutant versions of the virus that was supposed to have been edited out [10].

These unexpected outcomes of gene editing are only belatedly popping up because biotech scientists are so convinced that their gene editors are 'precise' that they test for the change they intended to make and fail to look for anything else. And, without that 'precision', the risks attaching to gene editing are infinite.

OUR COMMENT

This looks like there's not even a theoretical possibility that the foods produced by gene editing could possibly be safe. If they haven't acquired a novel ability to generate a toxin or an allergen or anti-nutritional qualities, they're likely to damage health by altering the healthy complement of microbes in our digestive system, or by providing a novel substrate for a novel microbial pathogen to flourish in. Or all five.

We suspect that Brexit has bred a gung-ho attitude to gene editing in our regulators. TELL THEM that they need to actually take a science-based approach, not just claim they're doing it. The safety of gene-edited foods has to be ascertained by toxicologists and appropriate biological and medical specialists using state-of-the-art techniques and valid animal models, not assumed on the basis of science-free claims made by plant genetic engineers or on the whims of the biotech industry. You can contact your MP and MSP using www.writetothem.com.

If you want more information, check out Gene Editing Myths and Reality - A guide through the smokescreen, prepared by Clair Robinson (GM Watch editor), 2021.

Background

[1] COURT RULES: GENE EDITING IS GENETIC MODIFICATION - September 2018

[2] CRISPR/Cas9 GENE EDITING - March 2016

[3] ERRORS IN CRISPR - November 2017

[4] CRISPR HAS IN-BUILT IMPRECISION - April 2018

[5] 'KNOCKING-OUT' A GENE CREATES A NEW ONE - July 2019

[6] CRISPR KNOCK-OUT OR KNOCK-ON? - March 2020

[7] NEW GENE EDITING, MORE OF THE SAME OLD THING - July 2019

[8] THE CRISPR WRECKING BALL REVEALED? - April 2019

[9] HORNLESS GENE-EDITED CATTLE WITH EXTRAS - November 2019

[10] THE GM CASSAVA MUTAGENIC MACHINE - July 2019

SOURCES:

• Question asked by Viscount Ridley, https://hansard.parliament.uk/Lords/2020-03-04/debates/935F12FF-1D8A-4449-8971-7B3B9E80B464/details, 4.03.20, Volume 802
• Eva Gelinsky and Angelika Hilbeck, 2018, European Court of Justice ruling regarding new genetic engineering methods scientifically justified: a commentary on the biased reporting about the recent ruling, Environmental Sciences Europe, 30:52 
• Michael F. Eckerstorfer, et al., March 2019, An EU Perspective on Biosafety Considerations for Plants Developed by Genome Editing and Other New Genetic Modification Techniques (nGMs), Frontiers in Bioengineering and Biotechnology 
• Scientist warns scrapping the EU's strict GMO rules threatens health, GM Watch 28.01.20

 Image Creative Commons