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Claims of safety and precision about gene-editing are contradicted by the science
Many scientific studies show that gene-editing can cause significant unintended genetic damage. Such damage could result in foods unexpectedly being toxic or allergenic.
Industry lobbyists and their allies in research institutes wrongly claim that gene editing of food is a new technology. However, a growing body of gold standard (peer reviewed) scientific research highlights unintended and potentially dangerous effects which are just as dangerous as old-style GM.
Science overwhelmingly supports the need for stringent regulation
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The published studies are listed below on this page and support the need for gene-edited plants, crops and farm animals to undergo as much strict safety assessment, regulation and labelling as other genetically modified (GM) food. See:  https://gmwatch.org/en/news/latest-news/19223
Gene-edited foods, like a wolf in sheeps’ clothing, are often wrongly described as safe and precise! There is a long list of published studies highlighting serious risks in the ‘unintended outcomes’ section below.
GM advocates falsely claim
that the products of gene editing from techniques such as CRISPR should not be classified as genetically modified organisms; do not require rigorous testing, because they are evolutionary, natural and carry no more risk than conventional plant breeding.
 The truth is that there is no evidence of safety because long-term feeding studies have been carried out in humans or animals and a substantial body of research shows a range of problems and risks.
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Dr Larry Gilbertson, a Monsanto Bayer Crop Scientist, has admitted that gene-editing techniques,  which the industry calls "New Breeding Techniques", are GM techniques and are "the same", in terms of the fact that they make changes in DNA. He adds that "there’s no intrinsic difference in the risk" between older-style GM and newer techniques.
He also says, contrary to frequent claims, that organisms obtained by gene-editing techniques are detectable.www.euractiv.com/section/agriculture-food/video/bayer-scientist-regulation-and-risk-assessment-must-evolve-with-technology

NEED FOR REGULATION

Surely developers test for problems?
Not necessarily – developers do not always look thoroughly for unintended (accidental changes) unless they are required by regulation to do so. Safety regulations must remain in place.
Many scientific papers demonstrate that unintended outcomes of the gene-editing procedure have serious implications for our food and require regulation
Published papers are listed in the ‘unintended outcomes’ section below – please scroll.
The unintended mutational (DNA damaging) outcomes summarized below occur after the gene-editing tool has completed its task of creating a double-strand DNA break. The mutations occur as a consequence of the cell’s DNA repair machinery, but the genetic engineer has little or no control over this.

So even if scientists eventually succeed in avoiding off-target mutations, most of the unintended mutations described can still occur at the intended gene-editing site.

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“These findings… imply, at the very least, the need for strong measures to prevent contamination by stray DNA, along with thorough scrutiny of gene-edited cells and gene-edited organisms... these are needs that developers themselves may not meet.”
- Jonathan Latham, PhD, Director of the Bioscience Resource Project commenting in Biotechnology, Commentaries, Health September 23, 2019
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“Understanding of uncertainties and risks regarding genome editing is necessary and critical before a new global policy for the new biotechnology is established." -Biswas S et al (2020), ‘Investigation of CRISPR/Cas9-induced SD1 rice mutants highlights the importance of molecular characterization in plant molecular breeding. Journal of Genetics and Genomics’.
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“The problems found with human and animal gene editing are increasingly being confirmed in plant gene editing. This lack of full control of the gene-editing procedure, as well as gaps in our knowledge of outcomes, points to the need for strict regulation of gene editing in food crops and farm animals.
“Regulation must start from consideration of the genetic engineering process used to create the gene-edited organism (“process-based regulation”), so that regulators know where things can go wrong and what to look for.” – Michael Antoniou, PhD, molecular geneticist.
New GM plants do not have a history of safe use and should not be exempted from biosafety assessments 

Warnings from leading scientists about new toxins and allergens

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Dr Michael Antoniou, London-based molecular geneticist, warns that “In the medical research community, it is not disputed that gene-editing techniques are GM techniques that give rise to Genetically Modified Organisms (GMOs) and that these procedures and their products carry risks that require strict regulation.” In the case of gene-edited foods and crops, the risks include the possibility of the presence of new toxins and or allergens.
https://www.euractiv.com/section/agriculture-food/opinion/the-eu-must-not-de-regulate-gene-edited-crops-and-foods
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61 leading international scientists have expressed grave concerns about unexpectedly high levels of toxins in gene-edited plant foods:“Even non-GMO plants are efficient at producing their own toxins – for example, to defend themselves against pests. The radical nature of the changes that can be introduced by NGMTs [new genetic modification techniques] could result in unexpectedly high levels of such toxins or in the production of novel toxins". See the full statement and signatories of the European Scientists for Social and Environmental Responsibility (ENSSER)
https://ensser.org/publications/ngmt-statement
Two prominent UK scientists warn about health risks from new toxins: 
Experts in gene editing and toxicology have recently written to George Eustice, Secretary of State for Environment, Food and Rural Affairs saying, “the likelihood of altered biochemistry in gene-edited food plants, with consequent health risks (toxicity, allergenicity) is very real”. https://www.gmwatch.org/files/Letter_from_scientists_to_George_Eustice.pdf
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Unintended outcomes and proven risks from gene editing

Explanation of terms used below

CRISPR = the most popular gene-editing tool
GENOME = the complete set of genetic material (DNA or RNA) of an organism
GENE =  a basic unit of inheritance within the genome of an organism
OFF-TARGET EFFECT = unintended genetic mutations that occur in gene editing and take place at a location other than the intended gene-editing site (hence “off-target”), including deletions, insertions, inversions, and rearrangements.
INDEL = insertion or deletion of DNA base units into the genome of an organism
BASE UNIT = the basic molecular unit from which DNA is constituted. There are 4 base units: adenine (A), guanine (G), thymine (T), and cytosine (C). In regions of the genome that encode for proteins, a sequence of base unit triplets (for example, CAG) makes up the genetic code.

MUTATION = Damage to a gene, resulting in a change to the genetic message carried by that gene, usually with harmful consequences to the organism.
The sequence is:


MUTATIONS > CHANGES IN GENE FUNCTION > ALTERED BIOCHEMISTRY > LIKELY NOVEL TOXINS/ALLERGENS OR HEIGHTENED LEVELS OF EXISTING TOXINS/ALLERGENS
SDN-1 = knocks-out a gene
SDN-2 = gene modification
SDN-3 = gene insertion

CHANGES INDUCED BY GENE EDITING ARE DIFFERENT FROM THOSE IN NATURE

Gene editing makes the whole genome accessible for changes – unlike naturally occurring genetic changes
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UNINTENDED MUTATIONS

Below is a selection of studies showing different types of unintended mutations resulting from gene editing that can affect the functioning of multiple gene systems. The consequences are an alteration in the plant’s protein and biochemical function, which could lead to poor crop performance and/or the production of novel toxins and allergens or higher levels of existing toxins and allergens.

Off-target mutations (genetic damage) in gene-edited plants Gene-editing tools, especially CRISPR, are prone to causing mutations (damage) to the organism’s DNA at locations other than the intended edit site ("off-target mutations"). This can alter the function of other genes, with unknown consequences to biochemical composition and function.The authors of this study noted, “development of plant genome editing has not yet fully considered potential off-target mismatches that may lead to unintended changes within the genome”. Wolt JD et al (2016). Achieving plant CRISPR targeting that limits off-target effects. The Plant Genome 9: doi: 10.3835/plantgenome2016.05.0047. https://www.ncbi.nlm.nih.gov/pubmed/27902801

Gene editing outcomes varied in efficiency, accuracy, and mutation structure, depending on the editing tool used and the genome targeted The authors of this study noted that of the editing tools examined, “CRISPR… is more susceptible to off-target effects and great care is required during target selection to minimize the likelihood of unwanted mutations”. Zhu C et al (2017). Characteristics of genome editing mutations in cereal crops. Trends in Plant Science 22:38–52. https://www.ncbi.nlm.nih.gov/pubmed/27645899
Large deletions and rearrangements of DNA at both off-target and on-target gene editing sites 
Large deletions and rearrangements of the plant’s genome, which can involve thousands of base units of DNA, have been observed following CRISPR gene editing. These mutations can affect the functioning of many genes, leading to alterations in the plant’s protein and biochemical composition.
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CRISPR gene editing in rice varieties caused a wide range of undesirable and unintended on-target and off-target mutations
This was an SDN-1 application of CRISPR that was only intended to knock-out a gene. In order to disrupt or knock-out the targeted gene, the researchers designed the CRISPR gene-editing tool to produce small indels (insertions and deletions of bases in the genome). However, what they got was quite different – large insertions, deletions, and rearrangements of DNA, raising the possibility that the function of genes other than the one targeted could have been altered. In addition, and surprisingly, the range of on-target mutations (unintended mutations at the intended editing site) varied, depending on the rice variety.

The authors warned that
"early and accurate molecular characterization and screening must be carried out for generations before transitioning of CRISPR/Cas9 system from lab to field" (something that is not normally done by gene-edited plant developers and would only be done if enforced by regulation). They added, “Understanding of uncertainties and risks regarding genome editing is necessary and critical before a new global policy for the new biotechnology is established". 
Biswas S et al (2020). Investigation of CRISPR/Cas9-induced SD1 rice mutants highlights the importance of molecular characterization in plant molecular breeding. Journal of Genetics and Genomics. May 21. doi:10.1016/j.jgg.2020.04.004  
https://www.sciencedirect.com/science/article/pii/S1673852720300916

COMMENT: The study confirmed that the types of mutations seen in gene-edited animal and human cells also occur in plants.

Höijer I et al (2021). CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations. bioRxiv. doi: https://doi.org/10.1101/2021.10.05.463186.
https://www.biorxiv.org/content/10.1101/2021.10.05.463186v1
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CRISPR/Cas9 gene editing can cause greater genetic damage than was previously thought
Potential consequences in gene therapy include triggering cancer.Kosicki M et al (2018). Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nature Biotechnology 36:765–771. https://www.nature.com/articles/nbt.4192
COMMENT: The CRISPR/Cas9 technique as used in plants is the same. In the case of food plants, the cancer finding is not relevant, but the types of changes seen in this study could result in unexpected toxicity or allergenicity.

Unintended large deletions of DNA, in some cases in excess of 500 base units, resulting from single CRISPR-induced cuts
In this study in human cells, in some cases, subregions of genes (“exons”), which carry information for the protein(s) for which they encode, were deleted. This resulted in the formation of novel gene structures encoding truncated forms of proteins.
Mou H et al. (2017). CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion. Genome Biology 18:108. DOI: 10.1186/s13059-017-1237-8. 
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1237-8
COMMENT: On the level of a whole living organism, such novel proteins could either be benign or harmful.

Unexpected types of insertions or deletions of DNA (indels)
This study looked at the molecular consequences of 17 CRISPR gene-editing events in four different gene regions of the mouse genome. The researchers found that CRISPR editing resulted in unexpected types of indels at all 17 sites in the mouse genome. Depending on the site being targeted, the size of the deletion was unexpectedly large.
Shin HY et al. (2017). CRISPR/Cas9 targeting events cause complex deletions and insertions at 17 sites in the mouse genome. Nature Communications 8, Article number: 15464. doi:10.1038/ncomms15464.  https://www.ncbi.nlm.nih.gov/pubmed/28561021
CRISPR gene editing for gene therapy applications can lead to massive damage to chromosomes
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Creation of new gene sequences leads to new RNA and protein products 
Alteration of the genetic code of the targeted gene can produce mutant forms of the protein it encodes for, new RNA, and new protein products. These outcomes can lead to changes in the plant’s biochemistry.
A Mou H et al. (2017). Genome Biology 18:108.
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1237-8

CRISPR-Cas9 gene editing produced unexpected new types of mRNAs (messenger RNA molecules) or proteins
When CRISPR was used to knock-out a gene function in human cells, instead of the intended outcome of destroying the function of a CRISPR-targeted gene, unintended insertions and deletions of DNA (“indels”) occurred. The indels resulted in an alteration of the gene’s DNA base unit sequence, so that it now produced new types of mRNAs (messenger RNA molecules) or proteins.
Tuladhar R et al (2019). CRISPR-Cas9-based mutagenesis frequently provokes on-target mRNA misregulation. Nature Communications vol 10, Article number: 4056, 6 Sept.    
www.nature.com/articles/s41467-019-12028-5

CRISPR edits intended to knock-out the function of a gene failed to do so – instead, proteins were still produced from the damaged genes
This study in human cells revealed a major unintended effect from the CRISPR-Cas9 gene-editing tool. Many of the proteins that were produced were still functional, but they were also mutant, which means they could gain a novel function, with unknown consequences.
Smits AH et al (2019). Biological plasticity rescues target activity in CRISPR knock outs. Nat Methods 16, 1087–1093.
https://www.ncbi.nlm.nih.gov/pubmed/31659326 Smits AH et al (2019).
Gene-editing process-induced mutations 
The gene editing process, taken as a whole (including plant tissue culture and GM transformation procedure), induces hundreds of unintended mutations throughout the genome of the plant. This can affect multiple gene functions with unknown consequences to protein biochemistry and metabolic activity.

In this study, the CRISPR tools in themselves did not introduce many off-target mutations, but many such mutations did arise from other aspects of the CRISPR genetic manipulation process taken as a whole – namely tissue culture and Agrobacterium infection.

Tang X et al (2018). A large-scale whole-genome sequencing analysis reveals highly specific genome editing by both Cas9 and Cpf1 (Cas12a) nucleases in rice. Genome Biology 19:84.    
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1458-5 
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Accidental insertion of foreign and contaminating DNA into genome at editing sites 
Following creation of a double-strand DNA break by the CRISPR gene-editing tool, the repair can unexpectedly include the insertion and rejoining of the broken DNA ends of the recombination template DNA used in SDN-2 and -3, or the insertion of contaminating DNA present in materials used in the plant tissue culture. This insertion of extraneous DNA in the genome of the plant, which can take place at off-target sites as well as the intended on-target editing site, has the effect of introducing new gene functions, as well as disrupting the function of host genes. These effects can combine to alter the biochemical function of the plant in unexpected ways.
Reports (Norris et al., 2020; Skryabin et al., 2020; Molteni 2020) describe insertion of the whole plasmid DNA molecules that acted as the recombination template for the SDN-2 or SDN-3 procedure. The insertion of these plasmid DNA templates will invariably result in at least one antibiotic resistance gene being incorporated in the genome, as these are a component of plasmids. This risks the transfer of antibiotic resistance genes to disease-causing bacteria in the environment and more worryingly, in the gut of the consumer, which would compromise medical use of antibiotics.
Antibiotic resistance genes in gene-edited cattle
In spite of the developer’s claim that gene-edited cattle were “free” of unintended effects, US food regulator FDA scientists found bacterial DNA in their genomes, including genes conferring resistance to antibiotics.
Norris AL et al (2020). Template plasmid integration in germline genome-edited cattle. Nat Biotech 38(2): 163-164
. https://www.independentsciencenews.org/news/fda-finds-unexpected-antibiotic-resistance-genes-in-gene-edited-dehorned-cattle
COMMENT: The antibiotic resistance genes in the gene-edited cattle could potentially transfer to disease-causing bacteria, adding to the huge public health problem of antibiotic resistance. The US FDA cited this finding to illustrate the fact that gene editing in animals can lead to unintended consequences and must be subjected to stringent regulation:
https://www.nature.com/articles/s41587-020-0413-7
    https://www.fda.gov/news-events/press-announcements/fda-expertise-advancing-understanding-intentional-genomic-alterations-animals
This SDN-3 (gene insertion) application in the cattle was being used by the developer to argue for deregulation of all gene editing in the US (including SDN-3)—something that the FDA is now resisting after their discovery. SDN-3 gene-edited organisms are not being currently targeted for de-regulation in the UK. However, if amendment 275 to the UK Agriculture Bill goes through, we will be subjected to unlabelled imports of gene-edited organisms from the US. If SDN-3 types of gene-edited animal do become de-regulated in the US, such animals and their products (meat and dairy) could be present in our food chain without GMO labelling. 
MEDIA ARTICLE: Molteni M (2020). WIRED, 24 July.
https://www.wired.com/story/a-crispr-calf-is-born-its-definitely-a-boy/
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Insertions of multiple copies of the DNA molecules used as a template for bringing about the desired gene modification
When the CRISPR/Cas system was used in an SDN-2 ("gene modification") gene editing procedure aimed at engineering insertion of genetic material in mice, a high frequency was found of insertions of multiple copies of the DNA molecules used as a template for bringing about the desired gene modifications. The researchers were concerned by the fact that the insertions could not be detected using standard PCR analysis. This in turn led to what they called "a high rate of falsely claimed precisely edited alleles" (gene variants). In other words, scientists have been unduly claiming precision for CRISPR when in reality it is not precise.
Skryabin BV et al. (2020). Pervasive head-to-tail insertions of DNA templates mask desired CRISPR-Cas9–mediated genome editing events. Science Advances 12 Feb 2020: Vol. 6, no. 7, eaax2941. DOI: 10.1126/sciadv.aax2941.    
https://advances.sciencemag.org/content/6/7/eaax2941

Unintended integration of foreign, contaminating DNA into the edited genome
This study found that DNA from the E. coli genome can integrate into the target organism's genome, as well as the vector plasmid, the 'delivery vehicle' that was designed to carry the CRISPR editing tool into the cells. The source of the E. coli DNA was traced back to the E. coli cells that were used to produce the vector plasmid. The study also found that plasmid and tissue culture DNA contaminants can be inserted by one of the cell’s DNA repair mechanisms into the genome targeted for editing, following a CRISPR cut. In this case, edited mouse genomes were found to acquire bovine DNA or goat DNA. This was traced to the use, in standard culture medium for mouse cells, of foetal calf serum and goat serum; that is, body fluids extracted from cows and goats. Even more worrisome, amongst the DNA sequences inserted into the mouse genome were bovine and goat retrotransposons (jumping genes) and mouse retrovirus DNA (HIV is a retrovirus). Thus gene editing is a potential mechanism for horizontal gene transfer of unwanted pathogens, including, but not limited to, viruses.    Ono R et al (2019). Exosome-mediated horizontal gene transfer occurs in double-strand break repair during genome editing. Communications Biology 2: 57
https://www.nature.com/articles/s42003-019-0300-2.pdf?origin=ppub
COMMENT: Jonathan Latham, PhD, director of the Bioscience Resource Project, wrote

https://www.independentsciencenews.org/health/gene-editing-unintentionally-adds-bovine-dna-goat-dna-and-bacterial-dna-mouse-researchers-find/ “These findings… imply, at the very least, the need for strong measures to prevent contamination by stray DNA, along with thorough scrutiny of gene-edited cells and gene-edited organisms... these are needs that developers themselves may not meet.”
Environmental problems resulting from GM crops
Landscape-scale distribution and persistence of genetically modified oilseed rape (Brassica napus) in Manitoba, Canada. https://pubmed.ncbi.nlm.nih.gov/19588180/
Long-term persistence of GM oilseed rape in the seedbank
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610060/
Modified genes can distort wild cotton’s interactions with insects
https://www.sciencenews.org/article/modified-genes-distort-wild-cotton-plant-insect-interactions

Gene-edited hornless cattle: Flaws in the genome overlooked https://www.gmwatch.org/en/106-news/latest-news/19084

100% of the scientific committee advising the Government have conflicts of interestsSee GM Watch’s report on the ACRE members’ declarations of interest:
https://www.gmwatch.org/en/106-news/latest-news/19999
Evidence that natural breeding leaves parts of the genome protected from changes
J. Grey Monroe et al. Mutation bias reflects natural selection in Arabidopsis thaliana. Nature. 12 Jan 2022. https://www.nature.com/articles/s41586-021-04269-6

The above summary is based on the list of studies compiled by GMWatch: https://gmwatch.org/en/news/latest-news/19499

For more details on individual studies, see also: 
https://www.gmwatch.org/en/news/latest-news/19223