"Natural GMOs" hype debunked

Research has found (yet again) that horizontal gene transfer happens in nature – but it doesn't show GM is "natural" or safe, say scientists

"Many plants are naturally GMO, research finds", trumpets an article on the pro-GMO Cornell Alliance for Science website.



It says, "Though much of the controversy around genetically modified crops is driven by the belief that the process of moving genes from one species to another is 'unnatural,' new research shows some 1 in 20 flowering plants are naturally transgenic.



"Dozens of plants, including bananas, peanuts, Surinam cherries, hops, cranberries and tea, contain the Agrobacterium microbe — the very same bacterium that scientists typically use to create GM crops."

But in reality, this research finding is neither new nor surprising. And contrary to the impression created by the article, the implications it has for GMO regulation are precisely zero.



The Cornell Alliance for Science article features a paper published in September in the journal Plant Molecular Biology (see abstract at the foot of this article). Researchers studied the genomes of some 356 dicot (flowering plants that have two seed leaves) species and found 15 naturally occurring transgenic species. “Thus, HGT [horizontal gene transfer] from Agrobacterium to dicots is remarkably widespread,” the authors stated. Horizontal gene transfer is the movement of genetic material between organisms, other than by the "vertical" transmission of DNA from parent to offspring.



The Cornell article suggests that the new finding should defuse much of the controversy around GM crops, on the basis that it shows that moving genes from one species to another is natural. The article goes on to mention a Danish scientist who has reportedly created a house plant using Agrobacterium, by an unspecified method, and believes that the plant should not be classified as a GMO.

New hype, old story

This is not the first time that GMO promoters have waxed lyrical about "natural" GMOs. A similar wave of hype was generated back in 2015, on the back of a research article announcing that the genome of a cultivated sweet potato contained gene sequences transferred from Agrobacterium through horizontal gene transfer.



The finding prompted a media article titled, “Genetically modified crops? Nature got there first: The sweet potato has been genetically engineered by bacteria”. The sweet potato finding is also cited by the new Cornell article.



In reality, however, the research finding regarding "natural" GMOs is, as we have said, neither new nor surprising, and there is nothing about it that would justify de-regulating GMOs. We explained why in 2015 in the wake of the sweet potato finding.



But either GMO promoters’ memories are short, or they hope that if they repeat the same lies and half-truths often enough, people will come to believe them. So for their benefit, and that of anyone who is tempted to believe them this time round, here, once again, is the explanation.

Natural horizontal gene transfer consequences happen over evolutionary time

Scientists have known for years that horizontal gene transfer happens in nature as well as in GM. But the crucial difference is that in nature, HGT and its consequences are selected for over evolutionary timescales: that is, over hundreds, thousands, or even millions of years.



That's not to say that HGT in nature is "safe". Even in nature, HGT might cause potential negative consequences that are completely unknown to the scientists who wrote the recent study and to everyone else.



With this in mind, London-based molecular geneticist Dr Michael Antoniou commented on the new paper, "We don't know what effects these natural HGT events had on the plants themselves or on consumers of the plants. It could have been disastrous. What we are seeing are the survivors.



"The authors say that 'This particular type of horizontal gene transfer (HGT) could play a role in plant evolution'. But it could equally have played a part in plant devolution – such as an inherited decreased fitness."



However, the saving grace of such HGT events occurring over long co-evolution between plants and their human and animal consumers has been that any harms are kept localised and limited. Humans and animals, as species, have had the time to learn which plants are safe to eat and which are toxic or otherwise dangerous.



But with GM, horizontal gene transfer is telescoped into an extremely short time period, and into a large global acreage of crops, without the benefit of co-evolution over long periods of time.

Irony

The irony of the latest PR messaging regarding the "naturalness" of genetic engineering is that originally, it was the critics of GM who originally flagged up the issue of HGT, pointing out that it meant genes deliberately introduced by genetic engineering into one organism might move into another by HGT. This concern was dismissed by GMO proponents, who, as Dr Michael Hansen, senior scientist at Consumers Union, noted below, either "denied that HGT happened or claimed it was unimportant".



Now the GMO proponents have adopted the reverse strategy and are hyping HGT as if it shows genetic engineering to be "natural" and safe.

"Natural GMOs" silenced the invading genes

One crucial finding of the new paper has implications that have apparently gone unnoticed by the authors and the Cornell hypesters. This is that most of the so-called "naturally transgenic" plants that were found to contain Agrobacterium transgenes had actually inactivated those transgenes. As the authors state, "the majority have stop codons". A stop codon is a structure within messenger RNA that signals a termination of translation into proteins.



Dr Antoniou explained: "The transgenes were inserted as intact functional genes. But as the plant evolved, the genes picked up mutations (DNA damage) that inactivated them. So the transgenes are not producing any full-length Agrobacterium protein but rather a truncated product with no serious functional consequence in the affected plants. This inactivation may explain why the transgenes have been tolerated by the plant.



"Producing a genetically engineered plant in the laboratory is quite different. You insert a transgene(s) that is specifically designed to persist in the plant and express. Over the past few years this has been helped along by a genetic engineering procedure called codon optimization, which in some cases can lead to higher levels of transgene protein production.



"In addition, when you have your GM plant, you introduce it into an artificial environment – agriculture.



"But with natural HGT, the consequences are selected for over an evolutionary timescale and in a natural environment, which brings to bear very different pressures of survival. And in this natural environment, in the majority of the "natural GMO" plants studied in the new research, the consequences were inactivation of the invading genes. Perhaps the plants that did not manage to inactivate the transgenes did not survive. And we simply don't know what happened to humans or animals that consumed them.



"Thus, the new research does not show that either HGT in nature or genetic engineering in the laboratory is safe, either for the plant that is engineered or the humans and animals that consume it."

"GMO sweet potato" quotes still apply

Here's what scientists told GMWatch in 2015 at the time of the sweet potato research publication and subsequent wave of hype. It equally applies to the latest PR messaging over the so-called "natural" GMOs.



Michael Hansen, senior scientist, Consumers Union, said:



“This paper validates what GMO critics have said all along: that horizontal gene transfer (HGT) is a potential risk of GM and must be considered as part of the risk assessment – yet it misleadingly presents this fact as showing that GM technology is safe.



“Historically, GMO seed companies have denied that HGT happened or claimed it was unimportant, since they were arguing against having to look for any unintended consequences due to the insertional mutagenesis associated with HGT.



“Indeed, I wrote the report, ‘Genetic engineering is not an extension of conventional plant breeding’, in January 2000 to draw attention to the risk of unintended consequences due to the insertional mutagenesis associated with HGT.



“The US FDA explicitly recognized this risk in 2001, when it proposed requiring companies to notify the government at least 120 days before commercializing a transgenic plant variety and named insertional mutagenesis as potential problem: ‘Because some rDNA-induced unintended changes are specific to a transformational event (e.g. those resulting from insertional mutagenesis), FDA believes that it needs to be provided with information about foods from all separate transformational events, even when the agency has been provided with information about foods from rDNA-modified plants with the same intended trait and has had no questions about such foods. In contrast, the agency does not believe that it needs to receive information about foods from plants derived through narrow crosses [in traditional breeding].’



“In other words, the US FDA admitted that there is a difference between GM and traditional breeding and that unintended consequences associated with insertional mutagenesis should be assessed. In spite of this, FDA is still following the 1992 policy (that there is no difference between GM and conventional breeding, a policy that came out of the White House Council of Competitiveness and was introduced at a BIO meeting by the then Vice-President Dan Quayle as a deregulatory initiative), rather than the 2001 policy.



“The notion that this natural engineering of sweet potatoes shows that GM technology is perfectly safe is false. Since we weren't around to document the early history of these sweet potatoes, we have no idea if they caused problems.



“Let's assume that the first ‘natural’ GM sweet potato, in addition to having some of the Agrobacterium DNA present, also, as an effect of insertional mutagenesis, caused a gene to be turned on that produced birth defects, sterility, or reduced fertility. As the further breeding occurred there would be variable levels of this particular toxin among sweet potatoes. People eating the sweet potatoes with high levels of the toxin would have fewer viable offspring, so the process of natural selection (the co-evolution of people and the food plants they are domesticating) would result in a shift toward decreasing the level of the toxin in sweet potatoes, due to the strong selection pressure against higher toxin levels.



“Since the Agrobacterium DNA has no direct link to the toxin, there would be no selection pressure to remove the Agrobacterium DNA. Thus it would persist in the modern traditional varieties developed from the initial naturally transformed sweet potato, enabling the team of scientists to arrive at their findings and write the paper under discussion. But far from reassuring us that genetic engineering is safe, all that can be concluded from the new paper is that the scientists have no idea what the history of the development of this sweet potato might be, or what effects it might have had on human or animal consumers during its evolution.



“Similar arguments have been raised regarding GM golden rice. Golden rice needs to be evaluated to see if levels of retinoic acid (a known teratogen), or any other potentially toxic retinoids, have increased in golden rice as an unintended effect. GMO proponents have argued that if high beta-carotene levels could lead to high retinoic acid levels and increased birth defects, why haven't we seen such problems with people eating carrots, or other foods high in beta-carotene? The answer is that humans have co-evolved with their food plants over time, so that if there had been varieties of carrots that caused such problems, there would be negative selection pressure against those traits so the toxin level would decline over time. With golden rice, there has been no co-evolution, so that's why it must be checked for potentially increased levels of potentially toxic retinoids.



“The scientists who wrote the sweet potato paper may not know the history of the HGT/insertional mutagenesis issue, and could be naively making the argument that natural HGT in the sweet potato means that crop genetic engineering is safe.”



Dr Michael Antoniou said:



“Maybe Agrobacterium genes did insert into the sweet potato genome. But then the genetic alteration was selected for fitness, advantage, and crucially, food safety for humans and animals over evolutionary time. This does not happen with GM crops. And the discovery that Agrobacterium gene sequences have ended up in the sweet potatoes does not equate with the artificial combinations of DNA sequences that make up the GM gene units that are introduced into GM crops. So this natural event cannot be likened to GM technology.”



Professor Jack Heinemann, University of Canterbury, New Zealand, said:



“This is an example of horizontal gene transfer (HGT). There is nothing unanticipated in this discovery because the process has been known to occur for decades and many other processes of HGT from bacteria to multicellular organisms have been demonstrated in the laboratory. So we’ve known for over a half century about HGT, even between kingdoms of organisms. Agrobacterium DNA in sweet potatoes isn’t ‘natural transgenics’; it's the outcome of a natural process.



“Ironically, especially in the 1990s many who were developing or selling GM crops attempted to minimise the frequency or effects of HGT. Indeed, they also tried to define it in ways that were so restrictive and unusual that it would be difficult to prove. When contradictions to this view inevitably appeared, it was reconstructed as evidence that HGT is common and therefore HGT from or to GM crops was no different than HGT from anything else. That somehow equated to it not being a new risk.



“The point is that when we move genes, we create organisms with no history of safe use and they should be tested for safety, consistent with international agreements. When people move genes into plants, we move constructs that we have pieced together from an average of 8 different species simultaneously. In my 25 years of work on HGT, I've seen no precedent for this kind of transfer so quickly. When HGT occurs in nature, nature has a chance to react, respond and adjust over many millennia to initially very small descendant populations. When we do it, nature is immediately bombarded by millions of hectares of new organisms in only a few years.



“Of course nature can also create organisms – by HGT or other means – that are capable of causing us harm. But that is no reason for us to do it unwittingly to ourselves. Nature can squash us with a rock from space, causing injuries indistinguishable from a car crash. This is not a reason to stop motor vehicle safety testing or recommend removing seat belts.”



Dr Ignacio Chapela, associate professor, University of California, Berkeley, said:



“There is nothing new here, and no surprises. We have known about this for almost forty years.



“What the authors of the new paper — and the reporters writing about it — claim as a surprise is based on the existence of a sequence incorporated over evolutionary time into the genome of a plant. This introgression implicated long processes of trial-and-error in a complex context which cannot be reproduced in the genetic engineering laboratory. The ‘thing’ resulting in the end may look similar, but the process and context through which that ‘thing’ came to be is what really matters.



“The people writing this paper know nothing about what processes led to the genomic transformation they encountered. They also know nothing about the processes (ecological, evolutionary, social) that these things may influence.



“They are content with describing the ‘thing’ instead of the process. At this level, they are right, just as defenders of crop genetic engineering are right when they make up true but irrelevant arguments to avert scrutiny of the safety of their work. They say, ‘DNA is DNA is DNA’, as if the chemical reality of the molecule was all that we needed to know — without acknowledging the role played by many other aspects, such as the DNA sequence.



“By this logic, a play by Shakespeare would be equivalent to an article in the tabloid press, on the grounds that both are made up of letters. But that would be nonsense. It is the sequence of letters, the words, sentences and paragraphs, and the context in which they are all placed that makes each work different from the other and lends a specific identity and function to each.



“This confusion between ‘thing’ and ‘process’ has been there all along since a policy decision was made in the US defining by decree and against reason that GMOs were ‘substantially equivalent’ to non-GM crops on the basis of their chemistry, not the biology of the transgenic manipulation.”



Let's hope that this time, the scientists' message hits home and the Cornell Alliance for Science abandons this particular thread of deceptive reporting.

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Widespread occurrence of natural genetic transformation of plants by Agrobacterium

Tatiana V. Matveeva, Léon Otten

Plant Molecular Biology, 21 September 2019

pp 1–23

https://link.springer.com/article/10.1007%2Fs11103-019-00913-y



Key message



Naturally transgenic plant species occur on an unexpectedly large scale.



Abstract



Agrobacterium-mediated gene transfer leads to the formation of crown galls or hairy roots, due to expression of transferred T-DNA genes. Spontaneous regeneration of transformed cells can produce natural transformants carrying cellular T-DNA (cT-DNA) sequences of bacterial origin. This particular type of horizontal gene transfer (HGT) could play a role in plant evolution. However, the material available today is not enough for generalizations concerning the role of Agrobacterium in HGT from bacteria to plants. In this study, we searched for T-DNA-like genes in the sequenced genomes of dicots and monocots. We demonstrate the presence of cT-DNAs in 23 out of 275 dicot species, within genera Eutrema, Arachis, Nissolia, Quillaja, Euphorbia, Parasponia, Trema, Humulus, Psidium, Eugenia, Juglans, Azadirachta, Silene, Dianthus, Vaccinium, Camellia, and Cuscuta. Analysis of transcriptome data of 356 dicot species yielded 16 additional naturally transgenic species. Thus, HGT from Agrobacterium to dicots is remarkably widespread. Opine synthesis genes are most frequent, followed by plast genes. Species in the genera Parasponia, Trema, Camellia, Azadirachta, Quillaja, and Diospyros contain a combination of plast and opine genes. Some are intact and expressed, but the majority have internal stop codons. Among the sequenced monocot species, Dioscorea alata (greater yam) and Musa acuminata (banana) also contain T-DNA-like sequences. The identified examples are valuable material for future research on the role of Agrobacterium-derived genes in plant evolution, for investigations on Agrobacterium strain diversity, and for studies on the function and evolution of cT-DNA genes in natural transformants.





