Gene Editing: Scientifically indefensible, anti-democratic, and harmful to trade

2 July 2020 — GMWatch

The amendment to the Agriculture Bill seeking to de-regulate gene-edited foods and crops should be discarded

An amendment has been tabled[1] in the UK House of Lords to the Agriculture Bill, seeking to change the definition of a genetically modified organism (GMO) in the UK’s Environmental Protection Act (1990) in order to exempt certain types of new genetic modification techniques, such as gene editing, from GMO regulations, within the context of “Agriculture Research”. This would mean that certain types of genetically modified organisms, including gene-edited ones, would escape safety checks and labelling. The Agriculture Bill will go to the committee stage in the House of Lords on 7 July.

The Environmental Protection Act (1990) defines a GMO as an organism in which “genes or other genetic material” have been “altered otherwise than by a process which occurs naturally in mating or natural recombination”[2] – in other words, by a process other than traditional breeding. This definition is in line with the EU’s GMO Directive 2001/18/EC as well as the international Cartagena Protocol on Biosafety.

The amendment was proposed by Lord Cameron of Dillington and others on 23 June. It aims to exclude from the definition of a GMO “products of breeding techniques where nucleic acid [DNA or RNA] changes could have occurred naturally or through traditional breeding methods”.

GMWatch opposes this amendment on the grounds that it will place public health and the environment at risk. But whatever one’s views on gene editing, there are problems with the wording, which is misleading as well as legally and scientifically unsound. Most importantly, we have serious concerns about the undemocratic and underhand way in which the amendment has been introduced.

Take action!

GMWatch has teamed up with GM Freeze and Beyond GM to produce a short political briefing and a detailed action briefing explaining why the amendment must be rejected. You can “Take Action” on the amendment on the websites of GM Freeze or Beyond GM.

Please circulate these links widely and share on social media.

Misleading and inaccurate wording

“Agricultural research”: Scope of amendment is unclear and the “research” specification is unfeasible

The amendment is headed “Agricultural research”. But it is not legally viable to have one definition of a GMO for research and another for the wider aspect of the commercial rollout. Thus it seems clear that whatever the intention behind this amendment, the re-definition of a GMO would sooner or later be applied across the board, including to the commercial rollout aspects – marketing GM food and feed to the consumer and selling seeds to farmers.

Even if the scope is restricted to research by the addition of specific wording, this would be unacceptable since it would be a Trojan Horse that would open the door to wider de-regulation of gene-edited foods and crops.

Indeed, the publicity for the amendment (e.g. in Guardian articles[3,4]) implies that the aim is to de-regulate gene editing in food and farming – and that it is not restricted to research. The amendment is unclear regarding its scope.

“Precision breeding” – neither precise, nor breeding

The explanatory statement published with the amendment refers to “precision breeding techniques”. But this wording is both vague and misleading. It is vague because “precision breeding” has no legal or scientific definition, though in the language of the pro-GMO lobby, it refers to gene editing techniques. It is misleading because gene-editing techniques are not breeding techniques. They are technically and legally speaking genetic modification techniques, as confirmed by the European Court of Justice ruling of 2018.[5]  Whatever one’s views on the EU and Brexit, this ruling is true to the science of gene editing.

Gene-editing techniques are also not precise, as demonstrated by a large and growing number of scientific studies.[6] These studies show that gene editing gives rise to numerous unintended effects, including mutations (DNA damage) at both off-target sites in the genome and at on-target sites (at the desired editing site). These unintended effects will change gene function, which in turn will lead to compositional changes in the plants. Potentially these could include the production of new mRNA molecules and new proteins, which could prove to be toxic and/or allergenic.

A large number of animal feeding studies with first-generation GM crops and foods show that they can have toxic or allergenic effects.[7] Will the same effects be found with gene-edited crops and foods? No one knows, as the toxicological studies needed to answer this question have not been carried out.

As just one example of the unpredictable and imprecise nature of the changes brought about by gene editing, a study (published in May 2020 found that CRISPR gene editing in rice varieties caused a wide range of undesirable and unintended on-target and off-target mutations (DNA damage).[8]

We do not know what consequences these changes might have for the health of the consumer as this was not investigated in the study, but the authors sound a strongly cautionary note. They conclude that CRISPR gene-editing technique “may be not as precise as expected in rice”. They warn, “early and accurate molecular characterization and screening must be carried out for generations before transitioning of CRISPR/Cas9 system from lab to field”.

These processes are generally not carried out on edited plants and will not be carried out by developers unless regulation requires it.

The authors of the paper add, “Understanding of uncertainties and risks regarding genome editing is necessary and critical before a new global policy for the new biotechnology is established”.

This is a sensible and science-based conclusion, the precautionary message of which is being ignored by those pushing for the de-regulation of gene editing, including the supporters of the amendment.

In addition, a statement signed by 61 scientists argues the need for strict regulation of the products of new genetic modification techniques such as gene editing in order to protect public health, the environment, and trade.[9]

“Could have occurred naturally”

The amendment assumes that the types of gene-editing applications intended for de-regulation produce changes that “could have occurred naturally”. This wording closely reflects the US’s recent “SECURE” rule on biotechnology, which exempts from regulation organisms produced with genetic engineering (including gene editing) when “The genetic modification is solely introducing nucleic acid sequences from within the plant’s natural gene pool or from editing nucleic acid sequences in a plant to correspond to a sequence known to occur in that plant’s natural gene pool”.[10]

It seems clear that the intention behind this choice of wording is to lower English food and farming standards to match those of the US, thus smoothing the path for a UK-US trade deal.

The problem is that the assumptions underlying both the amendment and the US rule are not supported by evidence. While proponents of gene editing claim that it gives rises to organisms indistinguishable from naturally bred organisms, no one has ever produced a gene-edited crop or food, sequenced its entire genome, and found an identical organism existing in nature.

If they did succeed in such a feat, they would be unable to patent the gene-edited organism (yet all commercialized GMOs are patented), since a patent requires an “inventive step” that does not already exist in nature. Gene-editing proponents appear to be playing a double game, telling the public and regulators that their products are natural, while telling patent offices that they are new organisms that could not exist in nature.

Gene editing is a laboratory-based artificial genetic modification procedure, which in no way resembles natural breeding. And the products of gene editing, if examined carefully, would appear very different from naturally bred products.

Gene editing involves introducing an enzyme into the target organism’s cells and aims to make a double-strand break at a targeted point in the DNA. The resulting double-strand DNA break triggers ‘alarm bells’ in the cell, which activates mechanisms to try to repair it. But neither the break nor the repair is a ‘clean’ procedure. As a result of errors in the editing process, the genome can be unintentionally altered, in that DNA is added, deleted, or rearranged.

These alterations are in effect genetic damage. They are known as mutations. The type and frequency of mutations are completely different from what can happen in nature.

Mutations happen in nature either through genetic error or through exposure to environmental stresses, such as radiation or chemicals. However, they occur at low frequency.[11] This is because most mutations are harmful to the organism,[12] so humans, animals and plants have evolved mechanisms for preventing and repairing them. In nature, mutations occur randomly across the genome. As over 97% of the genome does not consist of genes encoding proteins and thus is non-coding, most natural mutations will rarely hit a gene.

By contrast, the mutations induced by gene editing are not random but target functional gene regions. However, they target not only the intended editing site but also regions of the genome that are similar to that site. So unlike with mutations in nature, in gene editing there is a high chance that the induced mutations will disrupt other gene regions – causing off-target effects.[13]

As well as the off-target effects, gene editing causes a large spectrum of “on-target” unintended mutations at the intended editing site, including large deletions and rearrangements of DNA, which can affect the functioning of many genes.[14] In addition, the imperfect repair of the double-strand DNA break produced by the gene-editing tool can result in new gene sequences, resulting in the creation of new mRNA (messenger RNA) molecules and proteins.[15] The combination of all these different types of mutations disrupts the normal network of gene function, which can alter the plant’s biochemistry is totally unpredictable ways. This altered biochemistry raises the possibility of new toxins and allergens appearing in food.

New mRNA and proteins can occur naturally in plants. But in gene editing, due to the high frequency of large deletions and rearrangements of DNA as well as the creation of novel gene sequences, they are likely to occur more often and with more serious consequences.

In addition, in spite of claims that some forms of gene editing do not involve inserting foreign DNA, an unintended effect of these forms of gene editing has been found to be the incorporation of foreign DNA at the intended editing site. In one study, foreign DNA from bacteria, cattle, and goats was found to have inserted into the genomes of gene-edited mice. The contaminating cattle and goat DNA originated from the standard tissue culture processes that are used to develop all gene-edited organisms, including plants. The bacterial DNA came from the E. coli cells that were used to produce the plasmid, a DNA molecule commonly used as the vehicle to introduce gene-editing tools into the cells of the organism to be edited.[16]

Similar integrations of contaminating foreign DNA at the targeted site via gene editing have been found in many species, including fruit flies, fish, mice, yeast, Aspergillus (a fungus), the nematode C. elegans, the water flea Daphnia magna, and various plants.[17]

In another example of foreign DNA unexpectedly turning up in a gene-edited organism, gene-edited hornless cattle were found to contain bacterial DNA, including genes encoding for antibiotic resistance.[18] The risk is that these genes could transfer to disease-causing bacteria, adding to the huge public health problem of antibiotic-resistant diseases. The developer, a company called Recombinetics, had previously claimed that their animals were free from off-target effects[19] and had lobbied for de-regulation of such gene-edited animals on this basis.[20] Only an investigation by scientists at the US food regulator, the FDA, revealed the presence of the unwanted antibiotic resistance genes that the developer had missed.[19] As a result of this episode, the FDA is arguing for strong regulation of gene-edited animals.[22]

In nature, integrations of foreign DNA happen only rarely, in events known as “horizontal gene transfer”. But any effects would be selected for over evolutionary time, so that integrations having adverse effects on the organism would be selected out, via the affected organism dying or becoming unable to reproduce. Gene editing, in contrast, will result in vast numbers of edited organisms being released into the environment within a narrow timeframe. There is no safeguard of an evolutionary timescale that would enable us to select out the undesirable effects of the gene editing.

The range of unintended mutations described above (large deletions and rearrangements, creation of novel gene sequences, and insertion of extraneous contaminating DNA), which can take place at the intended gene editing site, can also occur at off-target sites where the gene editing tool has inadvertently cut the plant’s DNA. Therefore the complexity of gene disruption and function in a gene-edited plant can be large and the implications can be wide-ranging.

In conclusion, gene editing can scramble genomes in many ways and at many locations. In order to avoid serious impacts on health and/or the environment, developers of gene-edited crops and foods must check their products via whole genome sequencing, in-depth molecular profiling (“omics”) analyses to identify any potentially toxic or allergenic compounds or proteins, and animal feeding studies such as those required under EU law for old-style transgenic GMOs.

As shown by the example of the gene-edited cattle, GMO developers cannot be relied upon to check their products themselves. This is why strong regulation is necessary and why the amendment to de-regulate gene editing is misguided, dangerous, and not true to the science underpinning this technology.

Anti-democratic

The amendment was introduced in a way that allows a crucial issue with far-reaching implications to escape a full Parliamentary debate. If adopted, it would allow the Secretary of State to change the definition of a genetically modified organism (GMO) and de-regulate a large proportion of gene-editing techniques without further parliamentary scrutiny. Such a far-reaching change in our food and agriculture should be subjected to a full debate among our elected representatives in the House of Commons.

The proposed amendment suggests the Secretary of State should make his decisions after “public consultation”, but the scope and framing of any such consultation is unclear. It must be inclusive, accountable (for example, scientific evidence-based responses must be given to scientifically based objections to the amendment), and must not sideline social and ethical concerns. Also, it is unclear that public concerns raised during the consultation will have any real effects on policy.

UK public opinion is sceptical of GM, with a majority of Conservative voters supporting a ban on GM crops.[23] De-regulation of gene-edited foods and crops would remove safety assessment, traceability and labelling, depriving consumers of the choice of whether to buy and eat these GMOs and making it impossible to trace the cause of any allergic reactions or illnesses that may occur as a result of ingesting them.

Innovation

The UK government has consistently presented gene-editing technologies as “innovation”.[24] But gene editing does not reflect the whole of “innovation” in plant breeding, any more than it reflects the whole of the “science”. It is simply one technology among many. Some technologies are more desirable and effective than others, so society should be able to choose which technologies it supports.

And just because something is new, it doesn’t mean it’s desirable, or that it works. Finally, organic, agroecological, and non-GMO farming also use innovation. GM, including gene editing, doesn’t have a monopoly on innovation.

Risks to trade

The amendment only applies to England, yet the Environmental Protection Act that it aims to modify applies to the UK as a whole. De-regulating gene-edited crops and foods in England opens the strong possibility that Wales, Scotland and Northern Ireland may take a different view, leading to trade barriers between England and Wales, Scotland and Northern Ireland.

Trade issues will also arise with the UK’s major trading partner, the EU, since gene-edited organisms would be classed as GMOs in the EU but not in England.

The wording of the amendment (see above) appears to be designed to harmonize with the US SECURE rule and thus to smooth the way for a UK-US trade agreement that would lead to unregulated and unlabelled GMOs entering the UK food and feed supply.

Conclusion

While the wording specifies that the amendment applies to “Agriculture Research”, it is not legally viable to define genetic modification in different ways for different contexts. Thus the effect will be to de-regulate genetic modification across the board, from seed to fork.

The amendment is poorly thought out and scientifically indefensible, as it contains inaccurate and badly defined language. The amendment includes assumptions that are not backed up by evidence and that are actually contradicted by evidence. It is being introduced in an undemocratic way without the scrutiny of elected MPs in the House of Commons. It gives disproportionate power to the Secretary of State to make important changes in the laws that govern food and farming, again without full Parliamentary scrutiny. Moreover, the proposed public consultation on the amendment is unclear in scope and framing. If adopted, the amendment would create trade barriers with our major trading partner, the EU, and between England and the devolved administrations of Wales, Scotland and Northern Ireland.

The amendment should be discarded.

This article was written by Claire Robinson with technical advice from Dr Michael Antoniou.

More information and TAKE ACTION

GMWatch has teamed up with GM Freeze and Beyond GM to produce a short political briefing, and a detailed action briefing, explaining why the amendment must be rejected. You can “Take Action” on the amendment on the website of GM Freeze or Beyond GM.

 

Notes

1. https://publications.parliament.uk/pa/bills/lbill/58-01/112/5801112(i).pdf. The text of the amendment (p. 2) reads:
“LORD CAMERON OF DILLINGTON Insert the following new Clause—
“Agricultural research
(1)  The Secretary of State may by regulations modify the definitions contained in Part VI of the Environmental Protection Act 1990 in relation to products of breeding techniques where nucleic acid changes could have occurred naturally or through traditional breeding methods. 
(2)  Regulations under subsection (1) may only be made after the Secretary of State has held a public consultation on any proposed modifications to the definitions. 
(3)  Regulations under subsection(1) may only be made in relation to England. 
(4)  Regulations under subsection (1) are subject to the affirmative resolution procedure.”
“Member’s explanatory statement
“To enable the Secretary of State to make changes to the Environmental Protection Act 1990, as it applies in England, in relation to breeding techniques after the UK leaves the EU. This would allow for regulation of new precision breeding techniques compatible with international definitions.”

2. http://www.legislation.gov.uk/ukpga/1990/43/part/VI

3. https://www.theguardian.com/science/2020/jun/14/lords-seek-to-allow-gene-editing-in-uk-to-produce-healthy-hardier-crops

4. https://www.theguardian.com/science/2020/jun/14/british-farmers-need-all-the-help-science-can-offer-time-to-allow-gene-editing

5. http://curia.europa.eu/juris/document/document.jsf?text=&docid=204387&pageIndex=0&doclang=EN&mode=req&dir=&occ=first&part=1&cid=776006. Gene-editing techniques are called in the case “new techniques of mutagenesis”.

6. See a selection here: https://www.gmwatch.org/en/news/latest-news/19223

7. http://www.enveurope.com/content/27/1/4/abstract; http://sth.sagepub.com/content/early/2015/08/05/0162243915598381

8. https://www.sciencedirect.com/science/article/pii/S1673852720300916

9. https://ensser.org/publications/ngmt-statement/

10. https://www.aphis.usda.gov/aphis/ourfocus/biotechnology/biotech-rule-revision/secure-rule/secure-about/340_2017_perdue_biotechreg

11. https://tinyurl.com/ydert6dq

12. http://www.cs.unc.edu/~plaisted/ce/genetics.html; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17409186

13. See studies summarized here: https://gmwatch.org/en/news/latest-news/19223

14. See studies summarized here https://gmwatch.org/en/news/latest-news/19223; also https://www.sciencedirect.com/science/article/pii/S1673852720300916

15. https://www.nature.com/articles/s41467-019-12028-5; https://advances.sciencemag.org/content/6/7/eaax2941; https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1237-8

16. https://www.nature.com/articles/s42003-019-0300-2.pdf?origin=ppub

17. https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-015-0131-2 ; http://www.plantphysiol.org/content/169/2/960 ; https://cdn.elifesciences.org/articles/39468/elife-39468-v2.pdf

18. https://www.nature.com/articles/s41587-019-0394-6

19. https://www.nature.com/articles/nbt.3560

20. https://www.independentsciencenews.org/news/fda-finds-unexpected-antibiotic-resistance-genes-in-gene-edited-dehorned-cattle/

21. https://www.nature.com/articles/s41587-019-0394-6

22. https://www.nature.com/articles/s41587-020-0413-7

23. https://brightblue.org.uk/wp-content/uploads/2017/04/Green-conservatives-polling-report-Final.pdf

24. https://agritradenews.co.uk/news/2019/01/03/gove-champions-gene-editing-technology/

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