GM Free Cymru

Independent scientists fight back against concerted GM industry attack

Some time ago we published a brief note about this. It's yet another example -- now worth publishing in full -- of the idiotic tactics of the GM industry in seeking endlessly to discredit the research done by independent scientists on GM matters. What we are seeing -- over and again -- is fraudulent research published in tame journals and then accepted at face value by bodies such as EFSA which are supposed to be populated by competent scientists. This confrontational approach, accompanied by personal vilification in many cases, has as its object "the spreading of uncertainty", the conflation of issues which should be kept separate, and confusion in the minds of the public about whether GM is safe or not. But it has to be counter-productive in the long run, since members of the public have an instinctive dislike of personal vilification, especially where the victim is an independent scientist with no axe to grind, and the bully is a GM industry which has a great deal to hide. So three cheers for Angelika Hilbeck, Gilles-Eric Seralini, Ignacio Chapela, Andres Carrasco and many others for standing up to these industry-hired thugs who clearly do not know what science is all about, and who think that they can lie, and lie again, about the safety of their products in the hope that the public will eventually think that GM food is quite wonderful.

Commentary: Underlying reasons of the controversy over adverse effects of Bt toxins on lady beetle and lacewing larvae

Angelika Hilbeck, Matthias Meier and Miluse Trtikova

Corresponding author: Angelika Hilbeck Environmental Sciences Europe 2012, 24:9

15 February 2012

Abstract We outline important underlying reasons that fuel the decades-long controversy over adverse effects of Bt toxins expressed in genetically modified plants on beneficial, nontarget organisms. Inconsistent evaluation standards and asymmetrical levels of scrutiny applied to studies reporting significant adverse effects compared to those finding no adverse effects are described using the examples of the green lacewing (Chrysoperla carnea) and the two-spotted lady beetle (Adalia bipunctata). Additionally, the chosen style and concerted nature of the rather confrontational counter study and responses in the lady beetle cases bear striking similarities to other reported examples in the field of biosafety/risk science of genetically modified plants and to other fields of applied industrial techno- science that suggest deeper issues that go well beyond science. We call for a constructive and respectful scientific discourse where moving the frontiers of our collective knowledge forward takes center stage. Reported phenomena based on robust data must not be rejected or delegitimized on their being surprising and lacking an explained mechanism at the time of their discovery. Exploring mechanisms often requires entirely different expertise and methodologies than those of the discoverers. In particular, in biosafety/risk sciences, plurality of arguments and critical research approaches have to be embraced and actively encouraged rather than discredited or even silenced if we are to learn our 'late lessons' from past technology introductions.

Commentary In 2008/2009, Schmidt and colleagues [1] published a study reporting lethal effects of the microbial Bt toxins Cry1Ab and Cry3Bb on the biological control organisms Adalia bipunctata, a lady beetle. Based on this study and in concert with at least 30 other publications, Mon810 cultivation was banned in Germany in 2009. This policy response triggered two commentaries and one experimental study all published in the journal Transgenic Research that question the scientific basis of the German ban or claim to disprove the adverse effects of the Bt toxins on A. bipunctata reported by Schmidt and colleagues, respectively [2-4]. In a parallel paper, we report new data of a study that was undertaken to investigate the underlying reasons for the different outcomes and rebut some of the scientific aspects of the criticism voiced in the three publications. Here, we wish to take the opportunity to comment on some broader scientific aspects and issues that go beyond the experimental science delivered in the parallel paper. Given the strong language and the seemingly concerted effort we were confronted with in these three counter papers and, of course, in blogs and other fora, we find it justified, even necessary to, at least once, offer our evaluation and position on these criticisms.

In principle, we welcome the fact that our studies continue to stimulate debate and occasionally more research. However, it is unfortunate that the study by Alvarez-Alfageme et al. [2] was apparently set up primarily with the aim of disproving the results reported by Schmidt et al. [1]. Of course, any science has to withstand attempts at falsification just as any research result stands until new data emerges, pushing the frontiers of knowledge forward. However, the uncalled for, unnecessarily confrontational, and at times rather disrespectful unscientific nature of the language chosen obviously indicates deeper underlying issues. Other such confrontational responses and deliberate counter studies come to mind, as for example, the decades-long controversies on the risks connected with smoking, asbestos, or currently on-going bisphenol A and mobile telephones, where 'manufacturing uncertainty' has been well researched and documented, for example, by Michaels and Morforton [5]. We cannot know at present whether similar motivations drive the dogmatic 'refutations' which we find with respect to peer-reviewed results on potential harm from genetically modified organisms [GMOs], but reason alone forces one to wonder about this. More past examples of 'shooting the messenger' styles of responses following the publication of inconvenient research can also be found in the Late Lessons from Early Warnings: The Precautionary Principle 1896-2000 published by the European Environment Agency [6], which in hindsight clearly generated a lot of unnecessary damage and avoidable human suffering. Indeed, here is a striking precedent of a previous case as well, as Rauschen [3] also notes in his opinion piece but for other reasons. Similar counter studies were launched to disprove the reporting of adverse effects of Bt toxins on another predatory species, the green lacewing (Chrysoperla carnea), roughly 10 years ago. We argue that, in addition to the mentioned argument, double standards and asymmetrical levels of scrutiny are being applied to studies reporting adverse effects of Bt toxins expressed in genetically modified [GM] crops on nontarget organisms that continue to fuel the debate. In the following paragraphs, these points are explained and supporting evidence is provided.

Double standards: debated routes of ingestion/exposure The green lacewing, another important biological control organism, is also routinely tested for nontarget effects of Bt toxins for regulatory purposes in the approval process of Bt plants. The testing protocol follows closely the one used for pesticide testing which is based on the use of meal moth eggs that are coated with the test substance. Pesticides are externally applied on plants and insects and are often poisons that are taken up via skin or trachea (breathing apparatus) which is how they exert their effect. Bt toxins are gut poisons that must be ingested to unfold their effects. It is largely undisputed and has been pointed out for many years that the larvae of C. carnea are truly incapable of ingesting compounds deposited on the exterior of the eggs due to their very distinct, strictly piercing- sucking mouthparts (see Figure 1 for comparison of the mouthparts of C. carnea and A. bipunctata). We were among the first to point this out and express our concern about the inappropriateness of using coated meal moth eggs for testing Bt toxins [7].

To our knowledge, no comparable criticism has been published or voiced by the authors of the three papers discussed here regarding these obvious shortcomings in such trials that represent the prime data basis for safety assessments of Bt crops in the regulatory approval process. On the contrary, when we published our studies a decade ago revealing these shortcomings for green lacewing larvae and documenting that Bt toxins - both of microbial origin and of plant-origin - caused significant lethal effects in green lacewing larvae when administered directly or via prey into their gut using a protocol that ensured ingestion [7-9], they triggered a strikingly similar response involving some of the same authors of the Alvarez-Alfageme et al. paper [2]. Studies were published claiming to disprove the lethal effects of Bt toxins on C. carnea [10-12]. Also for this case, the differences in outcomes could be explained by the substantial differences in applied protocols and parameters measured [13], some of which bear resemblance to the protocols applied in this case of A. bipunctata (e.g., use of sugar solution and shorter exposure times). Rauschen [3] fails to acknowledge these pertinent issues when making reference to the green lacewing case. It is, however, quite interesting to note that the realization of the shortcomings we have been pointing out has at least been trickling into the regulatory requirements of the US Environmental Protection Agency [EPA]. This scientific deficiency is recognized in rulings like the following statement from 2007: 'In addition, it is questionable whether the green lacewings are ingesting the CryBb1 protein that is coated around moth eggs in a diet. Since green lacewings have piercing-sucking mouthparts, they may not be exposed to the protein on the external surface of the egg diet' [14]. However, instead of recommending tests with altered protocols that ensure ingestion of the Bt toxin, EPA recommends to drop this testing organism altogether and use instead another predator of the genus Orius [14] that has already been demonstrated not to be sensitive to Bt toxins (e.g., [15]). In addition, regarding lady beetles that are also routinely tested in safety trials for the regulatory approval of Bt crops, these were and still are often tested during the adult stage, which is inappropriate. It is undisputed that Bt toxins are gut toxins that exert their maximum effect during the juvenile stages of an insect. This shortcoming has also been recognized only years after the first commercial approvals by the EPA: 'EPA also believes, however, that lady beetle larvae would potentially have a higher risk of exposure to Cry2Ab2 than adults. Therefore, a dietary toxicity study will be required to determine the no observed effect concentration for lady beetle larvae... EPA has not previously required such a lady beetle larvae study for other registered PIP products...' [16]. For more details on these and other shortcomings in testing procedures for regulatory biosafety purposes of GM crops, we refer to an extended review by Dolezel et al. [17].

None of these obvious and recognized deficiencies led the authors of the three papers discussed here [1,3,4], nor the European Food Safety Agency [EFSA] for that matter, to apply a similar level of critical scrutiny as they have applied to Schmidt et al. [1] and other studies reporting adverse effects, when they deal with these regulatory biosafety studies that constitute the core data basis for regulatory approvals.

Level of scrutiny The above-described double standards reinforce the longstanding observation that in the GMO environmental risk assessment field, often only those studies that report adverse effects are subjected to 'extra' scrutiny by the regulatory science community and some scientist circles including the authors of the three papers discussed here. This practice has also been applied by EFSA and was confirmed in an interview with a former EFSA GMO panel member who stated: 'Of course, studies that describe potential negative environmental effects of GMOs are discussed particularly intensively' [18]. According to Millstone et al. [19], this practice is interpreted by the European public as an illegitimate support for the biotechnology industry, by the risk assessor. They state that 'greater institutional care was taken to try to avoid false positives than to avoid false negatives. That implies that critical scrutiny has been applied in an asymmetrical fashion that prima facie seems difficult to reconcile with a precautionary approach' [19]. The European Commission does indeed claim to follow the precautionary principle in all its regulatory appraisal processes.

Choice of language and displayed attitude Lastly, we cannot help but also notice the striking resemblance of the three concerted papers discussed here to the strategy extensively documented and described by Waltz [20] in her Nature article and summarized as follows: 'Papers suggesting that biotech crops might harm the environment attract a hail of abuse from other scientists. Behind the attacks are scientists who are determined to prevent papers they deem to have scientific flaws from influencing policy-makers. When a paper comes out in which they see problems, they react quickly, criticize the work in public forums, write rebuttal letters, and send them to policy-makers, funding agencies and journal editors.' We also find confirmation for the observation of an editor of the scientific journal Environmental Entomology after having been subjected to a similar ordeal with another 'problem paper' who states that 'part of what exasperates me is that they (the attacking scientists) have declared themselves to be the experts in this field and forcefully present themselves as the ultimate arbiters of truth' [20]. There is ample evidence for such a self-acclaimed 'arbiters of truth' attitude displayed 'forcefully' in all three publications [1,3,4]. As we find in particular those by Alvarez-Alfageme et al. [1] and Rauschen [3] unscientific, disrespectful, and thus, unacceptable for a proper scientific discourse, we do not repeat them here but refer to the original sources which also reflect on their preferred chosen outlet, the journal Transgenic Research. Needless to say that none of the attacked authors of the Schmidt et al. [1] study were informed prior to the publication of the three papers let alone offered the opportunity to defend and/or clarify their research, in response. This is one way a debate can be conducted but clearly not a constructive nor a properly scientific one at all. We hope that with both the scientific content of our follow-up study and the tone of this commentary, we have succeeded in setting a higher standard for scientific disagreement that aims to generate more and better knowledge, whichever way it may point in policy terms, rather than a more confrontational dogma. Better standards also include that at some point, one has to stand up to those who are not adhering to a common proper code of conduct and to reveal exactly that.

Scientists concerned with the environmental risks of novel technologies ought not to dismiss new knowledge/phenomena and delegitimize unexpected results based on their being 'surprising' and lacking an explanatory mechanism at the time of discovery, or possibly triggering policy responses one happens to disagree with. Scientific progress often comes about by first discovering and reporting an unexpected and inexplicable novel phenomenon. Only if that phenomenon is deemed of sufficient curiosity and importance do we embark on exploring the underlying mechanisms. More often than not, this requires entirely different expertise and techniques than those of the discoverers. It is indisputable that the lack of an explanatory mechanism does not - or rather, should not - invalidate an empirically established phenomenon. We have repeatedly established the phenomenon that Bt toxins can induce a significantly higher mortality in the two nontarget beneficial insects, green lacewings and the lady beetle A. bipunctata, with scientific data which are among the statistically and methodologically most robust that are published on this issue in the scientific literature to date (see the parallel paper to this commentary and Hilbeck and Schmidt [13] for extensive comparison of the statistical values and experimental methodologies). It is time to move beyond this dogmatic denial and 'killing the messenger' stage of the debate. Researchers with other expertise are now called upon to engage in research that genuinely aims at studying and elucidating the mechanisms of this established phenomenon and push forward our knowledge on modes of action of Bt toxins and modes of interaction (e.g., [21]) with other cofactors (e.g., [22]). After all, an increasing number of so-called 'stacked' Bt plants are reaching our fields and markets today that contain up to six Bt toxins, and hardly any of which have been tested for their combinatorial effects due to the 'lack of a known mechanism'. We find this a non-precautionary and insufficient scientific reason for simply foregoing the expenditure of testing, and perhaps even more importantly, possibly finding potential adverse effects, and thus, being able to prevent them.

(AH wrote the commentary. AH, together with MM and MT and along with the inspiration from numerous colleagues far beyond the circle of authors of this and the parallel science article, discussed and developed the arguments. All authors read and approved the final manuscript.)


REFERENCES (many accessible via hyperlinks from the original article) Schmidt JEU, Braun CU, Whitehouse LP, Hilbeck A: Effects of activated Bt transgene products (Cry1Ab, Cry3Bb) on immature stages of the ladybird Adalia bipunctata in laboratory ecotoxicity testing. Arch Environ Contam Toxicol 2009, 56:221-228.

Alvarez-Alfageme F, Bigler F, Romeis J: Laboratory toxicity studies demonstrating no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design. Transgenic Res 2010, 20:467-479.

Rauschen S: A case of 'pseudo science'? A study claiming effects of the Cry1Ab protein on larvae of the two-spotted ladybird is reminiscent of the case of the green lacewing. Transgenic Res 2010, 19:13-16.

Ricroch A, Bergé JB, Kuntz M: Is the German suspension of Mon810 maize cultivation scientifically justified? Transgenic Res 2010, 19:1-12.

Michaels D, Morforton C: Manufacturing uncertainty: contested science and the protection of public's health and environment. Am J Publ Health 2005, 95:39-48.

European Environment Agency: Late Lessons from Early Warnings: The Precautionary Principle 1896-2000. Environmental Issue Report. Copenhagen; 2001.

Hilbeck A, Moar W, Pusztai-Carey M, Filipini A, Bigler F: Toxicity of Bacillus thuringiensis Cry1Ab toxin to the predator Chrysoperla carnea (Neuroptera: Chrysopidae). Environ Entomol 1998, 27:1255-1263.

Hilbeck A, Moar W, Pusztai-Carey M, Filipini A, Bigler F: Prey- mediated effects of Cry1Ab toxin and protoxin and Cry2A protoxin on the predator Chrysoperla carnea (Neuroptera: Chrysopidae). Entomol Exp Appl 1999, 91:305-316.

Hilbeck A, Baumgartner M, Fried PM, Bigler F: Effects of transgenic Bt corn-fed prey on immature development of Chrysoperla carnea (Neuroptera: Chrysopidae). Environ Entomol 1998, 27:480-487.

Dutton A, Klein H, Romeis J, Bigler F: Uptake of Bt-toxin by herbivores feeding on transgenic maize and consequences for the predator Chrysoperla carnea. Ecol Entomol 2002, 27:441-447.

Dutton A, Klein H, Romeis J, Bigler F: Prey-mediated effects of Bacillus thuringiensis spray on the predator Chrysoperla carnea in maize. Biol Contr 2003, 26:209-215.

Romeis J, Dutton A, Bigler F: Bacillus thuringiensis toxin (Cry1Ab) has no direct effect on larvae of the green lacewing Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae). J Insect Physiol 2004, 50:175-183.

Hilbeck A, Schmidt JEU: Another view on Bt-proteins - how specific are they and what else might they do? mBiopesticides Int 2006, 2:1-50.

US Environmental Protection Agency Office of Pesticide Programs: Bt Cry3Bb1 corn biopesticide registration action document. [ ] website

Zwahlen C, Nentwig W, Bigler F, Hilbeck A: Tritrophic interactions of transgenic Bacillus thuringiensis corn, Anaphothrips obscurus (Thysanoptera: Thripidae), and the predator Orius majuscules (Heteroptera: Anthocoridae). Environ Entomol 2000, 29:846-850.

US Environmental Protection Agency Office of Pesticide Programs: Biopesticides registration action document. Bacillus thuringiensis Cry2Ab2 protein and its genetic material necessary for its production in cotton.
[http:/ / oppbppd1/ biopesticides/ ingredients/ tech_docs/ brad_006487.pdf] website

Dolezel M, Miklau M, Hilbeck A, Otto M, Eckerstorfer M, Heisenberger A, Tappeser B, Gaugitsch H: Scrutinizing the current practice of the environmental risk assessment of GM maize applications for cultivation in the EU. Environ Sci Eur 2011, 23:33. BioMed Central

EFSA: New Members for GMO Panel [ ] webcite

Millstone E, van Zwanenberg P, Marris C, Levidow L, Torgersen H: Science in Trade Disputes Related to Potential Risks: Comparative Case Studies. Seville: European Commission; 2004.

Waltz E: Battlefields. Nature 2009, 461:27-32.

Graf J: Shifting paradigm on Bacillus thuringiensis toxin and a natural model for Enterococcus faecalis septicaemia. mBio 2011. doi: 10.1128/mBio.00161-11

Then C: Risk assessment of toxins derived from Bacillus thuringiensis - synergism, efficacy, and selectivity. EnvironSci Pollut Res 2010, 17:791-797.