ACRE guidance document opens the door to a Wild West of unregulated GMO plantings. Report by Claire Robinson; technical advice by Dr Michael Antoniou
The UK government's Advisory Committee on Releases to the Environment (ACRE) has published its guidance on GM techniques that produce a hypothetical class of GMOs that it claims "could have been produced by traditional breeding techniques or could have arisen through natural processes".
The guidance, which is not legally binding, follows on from the statutory instrument passed by the Westminster government that exempts from the controls of the GMO regulations certain new GM plants ("qualifying higher plants" or QHPs) produced with technologies such as gene editing, for research purposes and other non-marketing uses, if the developers claim that they "could have" arisen naturally. Developers who intend to grow these experimental crops in fields will be allowed to self-determine if their plants are QHPs and they do not have to submit evidence to prove that they are.
We found the guidance shockingly irresponsible in three aspects: Its wide-ranging scope, its wilful disregard of the science that underpins new GM technologies, and its vague and imprecise language. In total, the document legitimises a "Wild West" of unregulated plantings by any Tom, Dick or Harry who is seized by a whim to play around with GMOs. The document is lazy, complacent and politically driven, and is clearly written to fulfill a predetermined agenda to smooth the path to market for a new generation of experimental GMOs.
Regarding scope, the guidance does not only exclude SDN-1 (gene disruption) and SDN-2 (gene modification) plants from the requirements of the GMO regulations, as we expected – but also SDN-3 (gene insertion) plants. In SDN-3, new complex genetic constructs known as transgenes, or other DNA elements, are inserted into the host plant genome, as with the older-style transgenic GMOs.
While some GMO proponents claim that SDN-1 and SDN-2 could happen in nature, no one, as far as we know, has claimed that SDN-3 can happen in nature. But ACRE claims that as long as there are “no transgene elements present, including the gene-editing cassettes, selectable markers and vector genes” in the final plant, it qualifies as natural.
In addition, cisgenesis, whereby the genes that are genetically engineered into the host plant come from the same or a related species that is sexually compatible (able to be bred together), is deemed to produce QHPs that are exempt from the requirements of the GMO regulation.
In fact, the only way that ACRE can suggest that all of these gene editing-induced changes (SDN-1, -2 or -3) could happen in nature is by ignoring the process through which they are made. When the gene editing process is considered, it is obvious that none of these could happen in nature. This is because gene editing is indisputably an artificial laboratory-based genetic modification procedure that bears no resemblance to processes that cause mutations in nature or natural breeding between sexually compatible plants.
Furthermore, as well as making the intended editing change, gene editing creates many unintended changes, in the form of DNA damage or mutations. Such DNA damage occurs at all stages of the gene editing procedure – plant tissue culture, introduction of the gene-editing tool into the plant cells (known as cell transformation), and as result of the action of the gene-editing tool. The action of the gene-editing tool can cause unintended DNA damage both at the intended edit site (on-target) and at other locations in the genome (off-target).
While ACRE cites some papers showing that there are a "broad range of genetic changes that result from natural processes and the dynamic nature of genetic material", they don't even try to prove that these natural changes are the same in quantity, quality, frequency, and effect as the changes induced by gene editing. And there is plenty of evidence that they are very different – studies show that that gene editing can create far-reaching changes that would be difficult or impossible to create through natural breeding.
And one Chinese study shows that in rice plants, the number of mutations from the tissue culture phase of the gene editing process, as well as the number of mutations from the insertion of the gene-editing tool using Agrobacterium, is far greater than the number in non-GM rice plants produced using natural breeding. Frequency is only one aspect of the risk equation, and the authors failed to use long-read whole genome sequencing to look for unintended mutations, but this study does show that in rice at least, gene editing is very different from natural breeding.
By ignoring the process by which a GM plant is made and focusing only on the intended product, ACRE is abandoning any pretence of responsible oversight of GMO releases. By analogy, solar, nuclear and coal-fired power stations all produce the same product – electricity – but only an idiot would conclude that all three types of station should be subjected to the same ultra-lax regulations. Clearly they have very different risks and these should be separately and rigorously evaluated, with a close eye on the details of the production processes involved.
Molecular geneticist Dr Michael Antoniou says, "This guidance shows that ACRE is not in tune with the latest concepts of molecular genetics. Even small changes in the genome can have wide-ranging implications for genomic network functioning."
Risks of scale
The potentially large scale of GMO plantings (even for non-commercial uses) means that any unintended changes that prove dangerous could have major negative consequences, as Heinemann and colleagues point out. This is unlike anything that could happen in nature or conventional breeding, where a harmful mutation in single plants or a given population of plants would be selected out by natural processes over an evolutionary timescale. That said, some of the effects of such mutations may have been serious – we don't know because we were not there.
In conventional breeding such mutations would be easily excluded from the breeding program. Plant breeders have been working with the same gene pool over centuries or millennia and know exactly what to look for in terms of elevated levels of certain known toxins or allergens.
GM, including gene editing, is very different. New experimental GM plants can be released on a large scale (e.g. in a field trial) and all at once. And due to the fact that GM can introduce new traits into plants, no one knows which toxins or allergens to look for. For this reason, generic testing should be done and the risks carefully assessed. But with the UK government's new absence of rules for non-commercial plantings, those tests will not be done and no environmental risk assessment will be carried out. So any harmful traits will pass unnoticed into the environment on a significant scale.
The tests that should be done – but won't be
Which tests should be done to try to ensure a basic level of safety for GMO releases? Dr Michael Antoniou advises that long-read whole genome sequencing to check for unintended changes in the DNA sequence, plus molecular analysis techniques – transcriptomics, metabolomics, and proteomics – to ensure that no unintended and potentially dangerous functional and compositional changes have taken place. If they have, it’s a strong indication that the plant's biochemistry has been altered in unexpected ways. That could include the production of toxins or allergens, higher levels of existing toxins and allergens, or altered nutritional value.
Dr Michael Antoniou, who uses these tests in his work, says they are widely available and not expensive to carry out: "Many labs have the capability to perform them. So there is no excuse for failing to do so. Why isn't ACRE requiring developers to do these tests in order to validate its position that the changes in gene-edited crops could happen naturally?"
The answer is, perhaps, because ACRE's whole house of cards – its assumption of the naturalness and equivalence of gene editing to conventional breeding – would collapse under the weight of the differences that would be revealed.
ACRE doesn't tell developers how to ensure no foreign genes are present
ACRE claims that as long as there are “no transgene elements present, including the gene-editing cassettes, selectable markers and vector genes” in the final GM gene-edited plant, then it can be assumed that the plant could have occurred naturally. But the big problem with this is that ACRE does not tell developers which tests it needs to carry out in order to ensure that these elements are not present. Long-read whole genome sequencing would do the job, but there is no legal requirement or even a recommendation that developers carry out such an analysis.
This could open up developers or the government to legal action, if some curious person decides to carry out the analysis that the developer should have done (but likely didn't) – and finds that "transgene elements" are left behind in the plant after all.
We know that while rogue transgene elements can potentially be removed by segregation, this isn't an easy process and developers may not try hard enough, especially as nothing in the UK government's new rules, forces them to do so. So fragments of foreign DNA, for example, from the plasmid vectors used to carry the gene-editing tool into the plant cells, can easily integrate all around the genome of the plant. Neither the developer nor the government will know they are there, if they haven't done long-read whole genome sequencing to look for them properly. And they won't do it unless they are forced to by regulations.
Depending on where the plasmid DNA fragments have inserted in the plant genome, gene functions could be disrupted, with unknown consequences to the plant’s biochemistry, composition, and safety.
Another problem with the ACRE guidance is that it assumes that SDN-1 type changes "arise through the same biological mechanism" as changes from natural processes and conventional breeding and therefore "precisely mimic" them. This position is no doubt based on the premise that the same DNA repair process (known as non-homologous end joining) is invoked when the DNA of an organism suffers a double strand break (cut across its double helix), whether the break arises from natural processes or gene editing.
What the ACRE panel conveniently ignores is that the process by which a DNA double strand break may occur in nature and through gene editing are completely different. So ACRE’s notion that SDN-1 gene editing outcomes “arise through the same biological mechanism" as may occur naturally is flagrantly incorrect and at odds with the scientific understanding of these processes.
Crucially, as noted above, there is no evidence that gene editing changes "precisely mimic" natural ones and plenty of evidence that they are very different. And SDN-1 gene editing changes certainly don't arise through the same biological mechanism as changes from natural processes.
In natural processes, three important causes of gene editing mutations are simply not present: tissue culture, the GM transformation process (which often uses the same techniques as in older-style GM), and the gene-editing tool itself. So this aspect of the guidance is simply a lie. There is no resemblance whatever to natural breeding.
Cisgenesis: Transgenesis by another name
ACRE claims that cisgenic plants are QHPs because "their genetic composition is consistent with the genetic variation that could occur naturally within that species or as a result of traditional [breeding] techniques".
However, as Drs Allison Wilson and Jonathan Latham of the Bioscience Resource Project point out, cisgenic plants are created using the same highly mutagenic plant transformation techniques used to create other transgenic plants. Wilson and Latham cite scientific findings that cisgenics can introduce important unanticipated changes that are not present in non-GMO parents or conventionally bred counterparts. Analysing the findings of several research papers, they conclude, "Remarkably, the results showed that trait introduction via a cisgene can result in plants which differ in unanticipated and dramatic ways from their conventionally bred counterparts. Furthermore, the observed differences would likely have important agronomic and ecological implications for commercial varieties."
What is more, cisgenic plants are not purely cisgenic – in other words, no supposedly cisgenic plant has ever been created using only DNA from its own or a closely related species. It is possible to isolate a gene from maize, for example, and then put it back into maize, but this will not be a purely cisgenic process. In order to put the gene back into maize, it has to be linked to other sequences from bacteria and sometimes from viruses, other organisms (potentially from different species), and even synthetic DNA. So “cisgenic” actually means “partly transgenic”.
Similarly, Wilson and Latham emphasise that “according to some definitions, cisgenes, like transgenes, may include anti-sense sequences, sequence changes to elude feedback inhibition and combinations of gene coding and regulatory components from different genes and species (Rommens, 2004). Indeed, the cisgenic plants engineered by Rommens et al. (2004), who claim to have made ‘the first genetically engineered plants that contain only native DNA’, were produced using Agrobacterium-mediated transformation of potato (via tissue culture and transient selection on kanamycin) and the cisgenes were composed of sense or anti-sense plant DNA from three distinct genes.”
Horizontal gene transfer
ACRE admits that cisgenic plants can contain foreign DNA but claims that “their presence may be discounted because exogenous [foreign] sequences are naturally present in the genomes of modern cultivated varieties, some of which are derived from widely divergent species, including from other phylogenetic kingdoms”.
As evidence, ACRE cites a paper showing evidence of two incidences of horizontal gene transfer (transfer of genetic material by a means other than the transmission of DNA from parent to offspring) of foreign genes into land plants. However, the researchers concluded that these events occurred early in the evolution of land plants – and in seed plants, the frequency of such events was found to have declined rapidly: "recently acquired genes specific to seed plants are relatively rare".
Horizontal gene transfer has long been known to occur naturally. But as evidenced by the paper cited by ACRE and as noted above (section, “Risks of scale”), horizontal gene transfer events have been selected for over an evolutionary timescale. Also, we do not know what harm these events may have caused at the time they occurred. Moreover, plant breeders would have quickly identified any isolated instances of toxic or otherwise problematic plants and excluded them from breeding programmes.
Environmental releases of gene-edited GMOs are a very different matter. Releases of plants with undesirable mutations could happen on such a scale that harm could be caused to the environment or (in case of contamination of non-GMO foods) health. This was recognised in the 2018 ruling of the European Court of Justice, which stated that new GM techniques “make it possible to produce genetically modified varieties at a rate out of all proportion to those resulting from the application of conventional methods of mutagenesis [methods used alongside conventional breeding]”. The court concluded that new GM techniques need to be regulated in the same way as any other GMO.
Therefore risks increase with scale – a point that ACRE fails to consider.
Lack of transparency
The first GM plant to be notified as a "qualifying higher plant" under the new system is a GM gene-edited camelina (false flax) from Rothamsted Research, engineered to have a modified seed oil content. The notification gives virtually no information on this GM plant. We, the public – as well as the government and the UK Genetic Modification Inspectorate that is tasked with monitoring QHP plantings for lack of compliance – have no idea which GM technology was used to make the plant and therefore the kinds of things that can go wrong in the GM process.
We also have no idea exactly what the introduced trait is supposed to do. This is a convenient omission for the GMO developers at Rothamsted, since if we don't know what the trait is meant to do, we won't know if it fails, as have other GMO experiments carried out in the UK. Under the new system, GMO developers can waste taxpayers' money at will, with no accountability to the public whatsoever.
There is also no information on the location of the planting, so the interests of organic and non-GMO growers are thrown to the wind.
This is the start of the "Wild West" in England for GMO developers. The total lack of transparency under the new rules marks a time in history where the GMO industry "went dark", keeping its products and their origins hidden in the name of avoiding public and scientific scrutiny and accountability.
The ACRE guidance succeeds in only one aspect: It expedites moving new GMOs towards more rapid commercialisation, meaning quicker profits and returns on patents for GMO developers. This should not surprise us, given that a GMWatch analysis showed that 100% of members of ACRE have actual or potential conflicts of interest with the biotechnology industry. So they may personally stand to gain from any weakening of the regulations around GMOs.
ACRE guidance not specific to bona fide researchers
Pat Thomas, director of Beyond GM, points out that one major weakness in the new regulations is that non-commercial GMO releases are not restricted to bona fide researchers or even to agricultural plants. In fact, the government has confirmed, in an answer to a recent written question, that there will be no prioritisation for particular types of non-commercial releases. She says, "What if a school wanted to plant a small crop as a learning tool for the students? Or someone wanted to plant an experimental crop on an allotment just for themselves? Or some promoter at a music festival decided it would be cool to have glow-in-the-dark GMO plants lining the perimeter or the route to the tents? I can't see anything that would stand in the way of such frivolous and unmonitored uses.”
More to come in the Queen’s speech
Currently the ACRE guidance applies only to non-commercial crops. However, as Beyond GM has pointed out, we are told to expect an announcement in the Queen’s speech, on 10 May, of new legislation on GMOs and this could include plans for the deregulation of commercial crops as well.
The ACRE guidance largely cites gene editing and other GM "proof of principle" outcomes (in other words, research that is still at an early stage) and expresses scientifically unsupported opinions and assumptions that these outcomes mimic what could have occurred naturally. In this way it justifies exempting them from regulatory oversight and protections.
ACRE fails to provide guidance on the route by which a gene editing developer can claim their product is a QHP. Where they do try to state QHP criteria (e.g. absence of foreign genetic material), they do not state which analytical methods should be used to prove this is the case.
ACRE ignores the GM gene editing process as a whole and thus turns its back on the scientific method – the bedrock of science and the evidence-based approach. By ignoring the GM gene editing process, ACRE conveniently fails to acknowledge the imprecision and unintended mutagenic effects of gene editing and their consequences.
In sum, ACRE is not only being unscientific but also negligent, and is assisting in the insidious process of putting business interests ahead of public health and environmental responsibility.