Metastasizing misinformation about GMOs and RNA: Ugly glare on Union of Concerned Scientists, Consumer Union
As the Genetic Literacy Project reports, the Union of Concerned Scientists, Consumers Union and prominent anti-GMO journalists are discouragingly but predictably silent after multiple science publications discredit an alarmist RNA study they had hyped. Wh

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Article Highlights

  • Can science self-correct, in effect protect against sloppy or politicized research?

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  • The important questions were whether RNA could affect human physiology and whether the study was reproducible.

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  • Some might call them professional fear mongerers.

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Can science self-correct, in effect protect against sloppy or politicized research? Scientists can try—but the success of those efforts depends in large measure upon the integrity of journalists and advocates to address their own reporting mistakes.

A great illustration of the challenge of controlling ‘metastasizing misinformation’ has emerged with the publication of a fascinating and important article in Nature Biotechnology that sharply challenges a study that had made controversial claims that dramatically raised the fear factor about GMOs.

The backstory provides an intriguing look at how the anti-GMO industry and sycophant journalists work—and the consequences of flogging single studies to score ideological points.

The controversy began when a Chinese research team led by Chen-Yu Zhang reported in Cell Research in 2011 that microRNAs from rice and other commonly eaten plants altered animal’s physiology in ways that could be harmful. The small pieces of RNA showed up in the bloodstream of both mice and humans, and in mice livers. The Nanjing University-based team concluded that this genetic material could bind to receptors in human liver cells and block the blood’s natural ability to remove LDL or “bad” cholesterol.

As biology PhD student Anne-Marie C. Hodge wrote in her Scientific American blog, “the revelation that plant microRNAs play a role in controlling human physiology highlights the fact that our bodies are highly integrated ecosystems.” To some degree, she suggested, ‘we are what we eat.’

Skeptical scientists and journalists push back

It was an odd finding, as it contradicted known science and numerous other studies. To objective observers, it was far from clear that microRNAs or miRNAs, which silence expression of their RNA targets, survives the digestive tract. As University of Toronto biochemist Larence Moran wrote in his blog last January, “This is one of those findings where the explanation doesn’t make a lot of sense but the data seem sound. It seems very unlikely that small plant RNAs … would find their way into the bloodstream where they could play a role in regulating mammalian gene expression. I think I’ll wait for confirmation.”

Those who reviewed the research also pointed out a host of problematic methodological issues, including a lack of negative controls. Apparently, Nature Biotechnology saw the criticism coming. Scientist and science journalist Emily Willingham outlined the prepublication drama in a fascinating account in The Scientist:

An editor at Science … rejected the manuscript because the discovery was “too extraordinary,” Zhang says—a response the group also received from Cell and Molecular Cell. The journal Cell Research accepted the report after a 2-year effort that included, according to Zhang, eight months of added experimental work to address reviewer critiques. Then, publication of the findings triggered concerns that small RNAs ingested from plants could affect how our bodies function, and unpredictable alterations in these molecules in GM plants might have unpredictable effects.

In other words, the important questions were whether RNA could affect human physiology and whether the study was reproducible.

The paper was received with skepticism by scientists, and because of its technical focus, was not given much initial notice by the news media. It was provocative and would certainly lead to scientific responses, challenges and follow up research to reinforce, modify or discredit the findings of the original paper. That’s how science should work.

But that methodical process was disrupted when food columnist Ari LeVaux, writing for The Atlantic in January 2012, wrote a bizarre article that twisted the science and injected misinformation into the GMO holy wars. Keep in mind that the original paper did not mention GMOs, and despite being prodded by LeVaux, the lead author of the study appropriately refused to comment on any implications about these findings for genetically modified foods. But that didn’t deter LeVaux and The Atlantic, which published his tirade under the ‘stick in your eye’ title, “The Very Real Danger of Genetically Modified Foods.”

“The work shows a pathway by which new food products, such as GM foods, could influence human health in previously unanticipated ways,” he wrote. “If miRNA can in fact survive the gut then it’s entirely possible that miRNA intended to influence insect gene regulation could also affect humans,” he further speculated.

LeVaux positioned his analysis as an attack on the doctrine of “substantial equivalence.” In 1991, well before any biotechnology products were ready for market, a team of independent scientific and regulatory experts convened by the Organization for Economic Co-operation and Development (OECD) had elaborated the rationale behind the concept. This doctrine—about which LeVaux clearly did not have a clue—directs regulators to focus safety assessment on compositional differences between a test variety and a conventional comparator; if there are no increased risks, compositional changes are irrelevant.

A few years later, the Food and Drug Administration adopted that view as part of its regulatory scheme. In other words, scientists concluded, the compositional changes in new DNA crops do not necessarily pose health or safety challenges not also found in organic or conventional farming. That also meant that genetically engineered foods would require no unique labels because genetic modification is just a process and the end products of crops grown from genetically modified seeds and traditional seeds are not materially different.

Anti-GMO echo chamber goes to work

In their battle to demonize crop biotechnology, anti-GMOers had long railed at this “substantial equivalence” principle. Now, with LeVaux’s strange twist on the Zhang et al. study, this new attack line gained steam. As University of Florida plant geneticist Kevin Folta recently wrote, “[T]he anti-GMO world ignited. In a discipline founded on what we don’t know will kill us all, the specter of a tiny, rogue RNA was quite frightening. … [T]he logical anti-GMO syllogism is that GMOs are bad,  GMO food has DNA, DNA makes RNA and RNA can be converted to microRNA. There. Bingo! Poison!”

In one of dozens of near hysterical posts that ricocheted through cyberspace, professional antis like Grist’s Tom Lakawy hyped LeVaux’s article and added additional doses of anti-GMO fear mongering. “I would argue that several studies have already suggested that existing GM foods might present a health risk,” he wrote, citing two studies that had long since been dismembered by the mainstream science community—key facts he omitted from his commentary. “[T]he Chinese study happens to involve exactly the kind of genetic material (sic)—microRNA—that biotech companies hope to use in their next generation of genetically modified foods. … Thus the news that plant microRNA can survive digestion and affect human systems brings into question the wisdom of pursuing this kind of technology in food.”

OK! Let’s just shut down all crop biotechnology!

Rather than interviewing independent scientists about the study, Laskway escalated the misinformation tsunami by trotting out comments from two dedicated anti-GMO science lobbyists. According to the Grist columnist, Doug Gurian-Sherman, senior scientist for the Union of Concerned Scientists, said that microRNA-based technology would require unimaginably high safety standards, which the biotech industry resists. Michael Hansen, Senior Scientist at Consumers Union, went even further, saying that the study “showed that the miRNA not only survived digestion [in humans] but also was taken up and moved to other parts of the body where a specific impact was noted. The studies you cited—from Seralini’s lab and Malatesta’s lab—only show that GE crops can have an adverse effect on animals.”

Both of those scare statements as well as the Laskway and LeVaux articles are speculative hogwash. Independent scientists and journalists—those with no industry connections or ideological skin in this debate but with a commitment to integrity and a knowledge of basic genetics—dismembered the LeVaux-Laskaway-anti-GMO thesis.

The paper does not even mention GMOs, let alone support the string of allegations embraced and publicized by professional antis. Christie Wilcox, PhD student in cell and molecular biology, writing on her Scientific American blog—she mockingly titled her piece “The Very Real Scaremongering of Ari LeVaux”—called The Atlantic article “completely unscientific” and filled with “horrendous inaccuracies.”

“Every plant and animal out there produces miRNAs,” Wilcox wrote—thousands of them in fact, as the regulate cells. They are in every food that we eat, which includes not only foods with genetically modified ingredients but also conventional and organic foods. In other words, despite the innuendo in Levaux’s article, they are necessary for normal cell function and there is no evidence to suggest that they support the ant-GMO activist thesis that GMOs are dangerous.

As Wilcox elaborated, the article focused not on any potentially unique properties of GMO foods but the potential side effects of non-GM food. “[W]hat the Chinese research team showed: that of the millions of miRNAs we eat every day, at least a few make it from our stomachs into our blood, and that a specific one from ordinary rice can change the expression of genes in mice.”

LeVaux, like many activist journalists and crop biotech opponents who have not done their biotechnology homework, proceeded to make hash of the science in an apparent eagerness to create an anti-GMO meme:

Ari [LeVaux’s] claim that ‘new DNA can have dangerous implications far beyond the products it codes for’ simply isn’t true because miRNAs are coded for. These small RNA fragments aren’t random or accidental – they are explicitly detailed within the genome. So a stretch of DNA that didn’t code any miRNAs before isn’t going to suddenly code for a ton of them when it’s placed in a different genome. If we’re worried about potential miRNA effects, we can screen genes we are considering transferring and determine if there is any chance they produce miRNAs before we shuffle around which organism they are in. [This is routinely done in sequence analysis.] Indeed, GMOs are tested … to ensure that the target gene has incorporated properly and that the organism is producing the desired [encoded] protein, and not unexpected products. Genetic modification is a very precise process, and there is no reason to think it would cause a sudden burst of miRNAs.

Push back by Wilcox and Willingham prompted appropriately chagrined editors at The Atlantic to distance themselves from the original piece with a public disclaimer. “[W]e’ve learned of the scientific inconsistencies made in Ari LeVaux’s most recent Flash in the Pan column, which is syndicated by a number of newspapers and magazine websites,” the update noted. LeVaux was forced to make numerous corrections. But key mistakes remain, and regardless, the damage to science and public discourse was done.

Replication studies rebuke ‘single study syndrome’

Since the publication of the original Zhang et al. study, similar research has appeared and the paper itself has been scrutinized—and the results are devastating. In May, researchers at Brigham and Women’s Hospital in Boston found that healthy athletes did not carry detectable levels of plant miRNAs in their blood after eating fruit filled with these molecules, and struck out in finding traces in mice or bees. “We conclude,” wrote the authors, “that horizontal delivery of microRNAs via typical dietary ingestion is neither a robust nor a frequent mechanism.”

Then in June, a research team from Johns Hopkins University writing in RNA Biology reported that the results were likely a false positive that resulted from the technique his group used, bolstering the case of skeptics who argued that genetic material from food would have little chance of surviving the digestive system, much less crossing the intestinal lining to enter the bloodstream.

The knockout blow came last week with the release of a replication study published in Nature Biotechnology. A team of scientists led by research scientist Brent Dickinson, using proper controls, could not detect the same microRNA reported by Zhang et al. Bottom line, there was almost none of the original culprit, miR168a, identified (one found in every million miRNAs).  Moreover, they repeated the rice feeding experiment, saw the decrease in LDL that Zhang et al. had found and the changes in LDL did not depend on the availability of miR168a. Instead, the authors added another treatment that corrected an energy/protein imbalance caused by the all-rice diet and the LDL effect went away. In turns out that the LDL effect was a nutrition effect. Mystery solved.”

Ignoring the basic science—few scientists embraced the original Zhang et al. study as it contradicted the logic of previous findings—professional antis will no doubt criticize the replication study as an industry apologia. “Many will dismiss this study because it was done with cooperation from Monsanto,” Folta wrote in his analysis of the newly released paper.  On the other hand, the other cooperator was miRagen [Therapuetics], a company interested in small RNAs for therapies.  They have a vested interest in identifying mechanisms to orally administer miRNA and detect physiological outcomes. If they repeated Zhang et al.’s work it would have been a positive finding for their company, as I’m sure they get plenty of criticism for the viability of their potential therapies.”

Nature Biotechnology did publish a rebuttal by Zhang and his colleagues, who trashed the replication study for what they called methodological problems, although the methodology used is well accepted in the literature and was incorporated in the Johns Hopkins and Brigham and Women’s Hospital studies. We’ll see how this all shakes out in coming months after Zhang et al. or another group show additional data.

Highlighting the importance of the new study by Dickenson et al., Nature Biotechnology editors wrote an extraordinary opinion piece underscoring the importance of not falling for ‘single study syndrome’ as anti-GMO alarmists are wont to do. “When an initial report prompts this level of concern and involves a considerable investment of time, effort and resources from both researchers and regulators in evaluating its findings and understanding its implications, then a carefully controlled and executed replication study clearly warrants publication,” the editors wrote.

Don’t hold your breath for rollbacks of their disgraceful journalism and public comments by LeVeaux, Laskway, Gurian-Sherman, Hansen and others whose statements have ranged from credulous to intellectually dishonest to fraudulent manipulation and misrepresentation of results. Expect chief GMO demonizer Jeffrey Smith—who is a charlatan—to continue to hype this unproven danger in his “analysis” of the “dangers” of GMOs. They are single study syndrome sycophants. As a group—and this includes a sizable cadre of web activists, organic extremists, foodie journalists and campaigning scientists—they cherry pick the handful of papers that support their point of view and ignore the vast majority of research that disagrees. Some might call them professional fear mongerers.

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