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New genomic techniques? We’ve been here before

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Exempting new GMOs from safety checks won’t solve our food and farming problems and would put health and the environment at risk, says Prof Michael Antoniou.

Here we go again (“Give genes a chance: Over 1,000 scientists in 14 countries demonstrate in support of gene editing”, EU Reporter, 6 February (https://www.eureporter.co/health/2024/02/06/give-genes-a-chance-over-1000-scientists-in-14-countries-demonstrate-in-support-of-gene-editing/). Whenever the world faces a food or environmental crisis, the use of genetic modification (GM), in one form or another, comes to the rescue. At least, this is what those who advocate the unrestricted use of these technologies in agriculture would have us believe.

First came “transgenic” commodity GM foods and crops (mostly soybeans and maize), introduced in 1996 – which, however, failed to deliver on their promises. They did not increase yields. They did not reduce pesticide use – they actually increased it over time. And they did not make farming easier, as weeds became resistant to the herbicides (specifically glyphosate) that the GM crops were engineered to tolerate, and insect pests developed resistance to the insecticide Bt toxin that GM crops were engineered to produce.

But wait a minute – we’re told that the new generation of GM crops (and animals) produced using so called “new genomic techniques” (NGTs) are different and will succeed where transgenics failed. NGTs, particularly gene editing, are touted in this way, since it is claimed that they make “precise” changes to the genome of an organism that mimic what can happen naturally through normal reproduction or natural mutation. The outcomes, we are told, are predictable, so NGT plant and animal products are completely safe. We do, after all, have the endorsement of NGTs by over 1500 scientists, including 37 Nobel laureates, in a letter (https://www.weplanet.org/ngtopenletter) spearheaded by the technophile lobby group WePlanet. And 37 Nobel laureates can’t be wrong… or can they?  

At this point, those of us who have been involved in the public debate on GM foods since its early days in the mid-1990s will be having a déjà vu experience. The use of transgenic techniques in GM crop development was presented as being precise and as a natural extension of traditional breeding. In addition, transgenic GM techniques were hailed as being more “precise” and as having more predictable outcomes, meaning that their products were safe to consume.

Have things really changed with the arrival of NGTs? If we look closely and deeply into NGT methods, there is sound scientific reason to doubt the recent hype surrounding the claims of precision, safety, and cure-all powers for this development.

The first thing to note about NGTs is that they are not, and have never been, banned in the EU. They are simply regulated – that is, like older-style transgenic GMOs, they are subjected to safety checks, traceability requirements in case something goes wrong, and labelling to enable consumer choice. It is these safeguards that the advocates of NGT “deregulation” want to scrap.

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The second thing to note is that NGTs are unquestionably another form of GM technology – an artificial laboratory method for altering the genetic makeup of a crop or animal. In common with older-style transgenic techniques, NGTs bear no resemblance to natural breeding methods. The claim of “precision” for NGT gene editing methods is based on the fact that developers try to make a targeted genetic alteration to an existing gene or targeted insertion of a foreign transgene. It is the targeted nature of genetic alterations to the organism’s genome by NGT methods that is at the basis of claims of that the technology is “precise” and only “mimics” what happens in nature. So why regulate something that can occur naturally, as advocates of NGT liberalisation argue?

What the advocates fail to admit is that NGT processes, including CRISPR-mediated gene editing, when considered as a whole (plant tissue culture, plant cell genetic transformation, and the action of the gene editing tool) are highly prone to large-scale, genome-wide unintended DNA damage (mutations). These unintended mutations include large deletions/insertions and large rearrangements of DNA affecting the function of many genes.

All genes work as part of a network or ecosystem. So changing just one gene can have major ramifications to the biology/biochemistry of an organism. In the case of NGTs and older-style transgenic GM methods, many gene functions will be altered. This will lead to changes in global patterns of gene function and altered biochemistry and composition, which could include the production of novel toxins and allergens.

But some may argue that any risks of that may be associated with NGTs are worth taking, as they can lead to higher yields or confer resistance to diseases or tolerance to environmental stresses such as heat, drought, and salinity, and in these ways help to combat world hunger.

However, traits such as these are genetically complex – that is, they have the functioning of many gene families at their basis. Indeed, they could be called “omnigenic” in nature. This type of massive, complex and balanced combinatorial gene function is far beyond what gene editing and NGTs in general can provide, which is the manipulation of one or few genes. Only natural breeding can bring about the large combinations of genes to robustly confer desirable complex traits.

Furthermore, scientific evidence shows that the gene editing process as a whole produces hundreds or even thousands of unintended, random DNA mutations, far more in number than the genetic variations that result from rounds of natural reproduction (https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1458-5) and natural mutagenesis.

And it’s not just about numbers, but where the mutations occur and what they do. The genetic variation that results from natural reproduction is not random. Crucial areas of the genome are protected (https://www.frontiersin.org/articles/10.3389/fpls.2019.00525/full) against genetic change. Any such change that does take place occurs (https://www.nature.com/articles/s41586-021-04269-6) in a directed evolutionary manner, as an adaptation response to the environment in which the plant finds itself. Any farmer who saves and plants their own seed can tell you that as the years go by, their crop performance improves as the plant’s genetics alter in a complex fashion to adapt to the farm’s conditions.

Therefore claims by developers of gene editing of crops (and animals) can end global hunger are not supported by our contemporary understanding of genome biology.

Any weakening of the regulation around NGTs, as advocated by the WePlanet letter signatories and others, ignores the genome-wide, large-scale mutational effects of the gene editing process and puts health and environment at risk. I’m not the only scientist who holds this view. The French food safety agency ANSES (https://www.anses.fr/fr/content/avis-2023-auto-0189) and the German Federal Agency for Nature Conservation (https://www.bfn.de/sites/default/files/2021-10/Viewpoint-plant-genetic-engeneering_1.pdf), as well as the European Network of Scientists for Social and Environmental Responsibility (of which I am a member) have also warned (https://ensser.org/publications/2023/statement-eu-commissions-proposal-on-new-gm-plants-no-science-no-safety/) of the dangers of exempting NGTs from the GMO regulations.

There have been no published studies assessing the health and environmental risks of any gene-edited foods, including those already marketed, such as the gene-edited tomatoes in Japan that are claimed to help lower blood pressure. This makes claims of gene-edited product safety unscientific, as any position should be based on solid experimental evidence – not presumptions, assumptions, or beliefs.    

In summary, the outcome from the application of NGTs is far from predictable, so a comprehensive, in-depth safety evaluation is required before marketing and the end products must be labelled for the consumer. The claims of precision, predictability, and safety are not true to the science that underpins this technology.

Prof Michael Antoniou, Professor of Molecular Genetics and Toxicology , Head: Gene Expression and Therapy Group, King’s College London. Faculty of Life Sciences & Medicine Department of Medical and Molecular Genetics, 8th Floor, Tower Wing, Guy’s Hospital, Great Maze Pond, London  SE1 9RT, UK

Email: [email protected]

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