Separating the chaff from the grain in the debate on GM wheat

By Guest Work 18/09/2012 71


By Prof. Jack Heinemann, School of Biological Sciences, University of Canterbury.

My report on assessing the risks of a form of GM wheat has sparked heated comment here and on other blog sites. The Sciblog-associated Science Media Centre (NZ) included comments from Peter Dearden and a link to the “Genetics Otago” blog along with comments made by Australian scientists.

For me, these events have raised some fundamental issues – not new ones but recurring ones – that have been confronting the scientific and regulatory communities at the forefront of developing, and critically evaluating, new technologies. I don’t pretend to have all the answers in this difficult area, and my views do and will continue to evolve. In the meantime, let’s pause to reflect on some issues.

The report being discussed was prepared for the Safe Food Institute and communicated by the associated Foundation in August 2012. Well over a decade ago, however, I took an interest in dsRNA-mediated gene silencing. In 2004 when I started actively engaging with regulators in Australia and New Zealand, I began advocating for testing for unintended dsRNA effects because of the possibility that intended and unintended dsRNAs might be transmissible through food.

Using assumption-based reasoning (that is, not using experiments to come to a conclusion), food safety regulators, including published scientists, dismissed the predictions, asserting that “the scientific evidence does not support the theory that RNA molecules in food can be transmitted” because they would be unstable during cooking, storage and digestion, unable to access mammalian cells or exert an effect on gene expression in mammalian cells (1). Our repeated calls to test these assumptions, and those made by others to the Australian Office of the Gene Technology Regulator, were met with, effectively, silence.

In 2011, a landmark paper published in Cell Research (4) proved these assumptions wrong (assumptions made, it should be noted, by the scientists serving both as regulators and as peer-reviewers for the regulator). The Cell Research paper concluded that “these results indicate that exogenous plant [dsRNAs] are able to enter the serum and organs of mammals via food intake, and that plant [dsRNA] can bind to the nucleotide sequence located in exon 4 of mammalian LDLRAP1, leading to the inhibition of LDLRAP1 expression in vivo.”

That dsRNA could cause silencing in humans was considered surprising to our community just 12 years ago, because of assumptions that it should not work in us, and because initial attempts to make it work in human tissue culture cells failed (2). It turns out that these assumptions were wrong, just like the assumptions that dsRNA would not transmit through food, and the failure in this case was due to using dsRNA molecules that were too long.

These anecdotes suggest that we shouldn’t lead with assumption-based reasoning when it comes to risk assessment.

Prof. Rick Roush said on the Australian ABC radio that he’d gladly volunteer to eat the GM wheat modified by dsRNA-mediated silencing techniques. He concluded that the potential for harm to humans was “very, very small.” Contrary to my report, which asks for safety testing to be done, entomologist Roush makes an a priori conclusion about the wheat’s safety.

This isn’t how risk assessment is done. The first step is what is sometimes called a “hazards” analysis. This analysis attempts to identify anything new, or anything produced at new concentrations, that might be the cause of an adverse effect. For the effect to happen, there must be exposure to the hazard. If exposure is a possibility, then the developer can be asked to determine whether the adverse effect is possible (or even probable), and to determine as much as possible what the severity of the consequences might be. Then the regulator makes a determination of whether the potential adverse effect can be mitigated or eliminated. If it can, or if the regulator then determines that harm to be negligible, the product may be recommended for testing or use.

That makes risk assessments at the stage of my report by definition speculative. And that is a good thing. It would be best to have identified what should be tested while the adverse effect is speculative rather than after a product causes harm to human health or the environment.

Prof. Dearden asks why, if people have been eating dsRNAs from plants (as shown by the Cell Research paper), should a test on those created in GM wheat be done. We have already answered that question in a peer-reviewed and published article in the risk assessment literature. “Likewise, as GMOs modified by regulatory RNAs (e.g., dsRNA of the siRNA, antisense, and shRNA kind) grow in number, it will be critical to determine the on and off target effects of the novel RNA” (3).

The sequence and the structure of the dsRNA intended to be produced in the GM wheat has never been eaten by humans before. We have no way of knowing if this molecule is benign, beneficial or harmful. We don’t have a history of safe use of this wheat. “Neither overall amounts of small RNA molecules, nor the presence of benign small RNAs in conventional plants are sufficient as evidence that all novel small RNAs will be safe in the food chain or environment” (3). The potential effect is caused by the sequence and the sequence is unique to the GM wheat.

This begs the question then, whether Roush and other commentators’ conclusions were risk assessments or risk conclusions. If the latter, then these should be based on open, reviewed and accessible methodology. Indeed, to say that harm is unlikely is a claim that many would feel should have gone through anonymous peer-review and have been published in a journal.

Interestingly, risk assessments are rarely if ever published in journals following an anonymous peer-review. For example, it is not FSANZ’s policy to do so. Regulators use almost exclusively unpublished material from the developer at the time they make their decisions. Why are there no objections to the lack of anonymous peer review and journal publication here, especially as these assessments, unlike my report, will actually determine what goes into the food supply?

Again, in contrast, my report on a risk assessment met the same or higher criteria for peer review that regulators and the industry use routinely. Unlike their work, my report had no potential to put an unsafe product in front of the public, and was open to complete public review. Yet it was criticised for not appearing in a journal.

Worse than this, many commentators who addressed my report in the media chose ad hominem argumentation rather than discuss the outlined exposure pathways and the nature of the experiments that are needed to test legitimate hypotheses about what and how adverse effects could arise. They made mistakes, such as failing to check facts on where the target gene had come from.

Importantly, not a single commentator to my knowledge has offered any evidence that a risk assessment on the dsRNA molecules, or secondaries that might arise, was done by anyone. Much less have they offered even a single shred of data from any testing specific to this risk of the GM wheat.

Science routinely shows prevailing assumptions, such as those made earlier about dsRNA, to have been wrong.  The proper response to challenges to assumptions is further research.  This, not denunciation of the challengers, is the way to maintain public trust in the regulatory system, and in science.

 

1.         FSANZ. 2006. Draft Assessment Report Application 549 Food Derived from High Lysine Corn LY038. Food Standards Australia New Zealand.

2.         Gura, T. 2000. A silence that speaks volumes. Nature 404:804-808.

3.         Heinemann, J. A., B. Kurenbach, and D. Quist. 2011. Molecular profiling — a tool for addressing emerging gaps in the comparative risk assessment of GMOs. Env. Int. 37:1285-1293.

4.         Zhang, L., D. Hou, X. Chen, D. Li, L. Zhu, Y. Zhang, J. Li, Z. Bian, X. Liang, X. Cai, Y. Yin, C. H. Wang, T. Zhang, D. Zhu, D. Zhang, J. Xu, Q. Chen, Y. Ba, J.-J. Liu, Q. Wang, J. Chen, J. Wang, M. Wang, Q. Zhang, J. Zhang, K. Zen, and C.-Y. Zhang. 2012. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res 22:107-126.

Correction: reference to Australian Science Media Centre Changed to NZ Science Media Centre


71 Responses to “Separating the chaff from the grain in the debate on GM wheat”

  • There is a prevailing regulatory and industry attitude that continually shocks me – that industry should be allowed to sell whatever products it likes, with meagre in-house precautionary study (and I have supposed only enough to protect short-term corporate financial interests), until such products are demonstrated to be unsafe. Our children are industry’s frontline and remain there until conditions arise where so many children, babies, adults are hurt that epidemiological science is demanded.

    I’m grateful for Jack Heinemann’s efforts over years, as I now read, to have novel genetic products appropriately investigated before food approval and/or environmental release.

    I’ve read a lot of food applications to FSANZ – no peer reviewed research in my experience – just material from the agri-giant. MADGE put out a media release on one such FSANZ-approved crop on the topic discussed http://www.madge.org.au/Docs/MR-110329-All-aboard-the-Hindenburg.pdf

  • I think your second sentence,

    “The Sciblog-associated Australian Science Media Centre published excerpts from Peter Dearden’s “Genetics Otago” along with comments made by Australian scientists.”

    want to read,

    “The New Zealand Science Media Centre published excerpts from Peter Dearden’s Genetics Otago blog on this site along with comments made by scientists sourced by the Australian Science Media Centre.”

    Objecting to ad-hominem arguments is one thing, but calling Kiwis Aussies is another…! 😉

  • Peter, I worried about you taking that inference. Let me make it absolutely clear to you and all readers that I was not referring to you. My view is that you have been critical but not personal. Thanks for raising the issue so that I had a chance to make that statement.

  • Please correct me if I’m wrong, but I get the impression, that on the scientific aspect of this, Peter and Jack, that you are not to far separated on this issue. That is, that CSIRO need to make sure that they are not using sequences that found in human’s. The major difference that I can see here is that Prof Heinemann is specifically calling for risk assessments to be public and peer reviewed whilst Prof. Dearden simply notes that the secrecy of the process passing through the regulators is problematic. Not a huge difference as far as I can see.

    The major criticism offered by the post on Southern Genes, was that the manner in which the information was delivered was unhelpful, that rather than engage in the process, it was confrontational. This piece doesn’t, in my eye answer that, I’m not sure if it was intended to.

    It does raise a couple of interesting points though. The idea that risk assessments should be published after anonymous peer review is a good one. While I would concur that a public report offers a higher level of transparency and offered a … better possibility for peer review (sorry that sounds odd, I hope you can see what I’m getting at), is it sufficient, if not held to the same level as is requested of the risk assessments.

    Another point occurs to me, reading all of this. Is presenting a risk assessment to the public an appropriate forum? I’m not suggesting some paternalistic reign of censorship. The impression I get though, is that this gets presented as “Academics agree that GE is bad/dangerous” rather than a discussion of actual risks and arguments for/against. It comes across as an appeal to authority rather than a genuine presentation of risks. Primarily I think, because while any risk assessment presented to the public may be accurate and worthy of discussion, rarely is it presented with any depth to the general public.

    I suspect that the argument we should be putting forward to the public is that pressure should be put on the regulators to publish the risk assessments and laying out the problems and risks with not doing so.

    Apologies for the length.

  • To be responsible for the circus of misinformation you spawned by press release is just beyond comprehension: http://safefoodfoundation.org/wordpress/?p=946
    “Expert scientists warn that genetically modified wheat may cause Glycogen Storage Disease IV, resulting in an enlarged liver, cirrhosis of the liver, and failure to thrive. Children born with this disease usually die at about the age of 5.”

    That is baseless. People now have less understanding of this issue and more fear than they did before. You own this misinformation: http://screencast.com/t/KTmJp1MFq1z . I hope this escapade will be used in the future as a model for how *not* to communicate science to the public. It’s shameful how you misused the fears of people who don’t understand the science.

    This circus managed to be simultaneously appalling and hilarious. When David Icke promotes your claims, you ought be worried. But it did provide some humor at least.

    It’s all founded on speculative claims based on a flawed sequence analysis. You deliberately chose to misuse the sequences to inflate the claims. You absolutely had to know that choosing an enormous 25000 nucleotide sequence was incorrect. The construct is specifically called out on the OGTR page as having “partial” sequence http://screencast.com/t/RX7KzyrrN . Your analysis is loaded with “chaff” precisely because of this.

    Further, the reliance you place on work from one paper that has yet to be confirmed by other hands is unwise. Demanding policy decisions on preliminary work (as you might note from the early work you decry in this post) is unjustified.

    It was incredibly irresponsible to misuse the public trust in this way.

  • Thanks Jack, I appreciate the clarification.

    Tirohia, I think you are correct, Prof Heinemann and I are not so far apart on the the front end of this issue, the risk assessments. We need more clarity and transparency around risk assessment issues, not just for GM crops. The instinct for secrecy with our regulatory bodies makes it hard to have trust, and trust is the key issue. In this case, if I could trust that the agencies have addressed the concerns Prof Heinemann has raised, I would be happy. But on what basis do I form that trust?

    Surely we can think of better systems in which openness engenders trust? The requirements of intellectual property and secrecy should not trump disclosure when a company, or other, is trying to get permission to sell us their products.

    NZ is a small, innovative country, not always in thrall to commercial interests. Please tell me why there is some reason WE cannot have openness, and thus trust, in our regulators?

  • If the science indicates that there is potential for harm, then I don’t see why commercial sensitivity should come into it – the vendor either fronts up with details of whats going on or goes home. As you say, this shouldn’t be limited to GE crops.

    It would be nice if one of the roles of the regulators were to arrange for peer review and maintain a repository of all reviewed risk assessments for each product that comes before it. Secrecy does not engender trust though and I without transperancy on things like this I can’t see it getting any better.

    My big fear with this particular instance, is this will be misapplied and used as a stick with which to beat all GE products with. Again, I don’t see how things improve without transperancy.

  • I’m willing to put aside the discussion of the egregious PR campaign for now. There’s really nothing that could be said to make that forgivable anyway. That horse is out of the barn and around the world.

    Let’s focus on the data and claims in Jack’s analysis, which forms the foundation for the whole shebang.

    If everyone could turn your attention to Appendix 1. This is a comparison of the human GBE gene and GenBank sequence AF525764.1 which contains several components, including the SBE1 gene at the 3′ end (annotated gene begins at 19586). Here’s the link to the record at NCBI: http://www.ncbi.nlm.nih.gov/nuccore/AF525764.1 Clearly it’s annotated to indicate several components. Note the “gene” part that is not “pseudo” begins at 19586.

    [Note: the Appendix 1 header appears to claim it is a comparison vs the NR database, but I don’t think that’s what is shown here. Maybe Jack can clarify how that was done so everyone could give it a try.]

    Question 1 for Jack: did you really believe that the construct would contain that whole 25000 nucleotide sequence? Was that reasonable and likely based on what we know from similar experiments and from the OGTR information you linked in the report?

    Question 2 for Jack: What happens to your analysis if only the “gene” part is used? Does 90% of Table 1 vaporize? Poof? For those of you playing along, see Table 1. Any piece of the SE1 sequence before 19586 would be in the pseudogene/other section.

    Let’s start there and see what the answers are before we go further with the assumptions and analysis. I want to hear the answer to Question 1 first.

  • Tirohia

    Your posts are definitely contributing to my evolution!
    My report is not the first nor the last to be paraphrased by others. Nor is it exceptional in inspiring paraphrasing. On the other side, this would be what is the intent of product claims – both pre and post commercialisation – promoting their actual or their speculative benefits. When these claims are false, they can also affect millions and cause real harm, financial to consumers if nothing else.

    As the European Network of Scientists for Social and Environmental Responsibility write: “And we note that when CSIRO in its response says, ‘High amylose wheat has increased levels of resistant starch, which could have positive benefits for bowel health and people with diabetes”, this is also ‘speculative’.”

    As I try to say above, this is not the first time that I or others have attempted to bring to the regulators’ attention a rationale for requiring risk assessment protocols that directly test for any potential adverse effects of the dsRNA. My report should be of no surprise to them. This kind of testing, moreover, is permitted under international guidance from the Codex Alimentarius. I’ve also published in a journal following anonymous peer-review the same rationale for testing dsRNA.

    So you raise an excellent question for me: when is it appropriate for scientists to engage more directly with the public? This boundary has long ago been transgressed by the commercial sector, using scientists and writings of scientists in ads and other ways. And this very blog site is an attempt to bring scientists in contact with the public. It seems to me that the issue isn’t about scientists engaging the public, but what some think of the message.

    And the other side of the question is when is it not appropriate to conceal information from the public, especially information that reveals uncertainty or disagreement between scientists?

    As I said under Peter’s blog, we have common ground in seeking greater transparency in the official risk assessment process, which bases decisions on unpublished data from product developers.

    Should this data have gone through anonymous peer-review and publication prior to risk assessment? I actually would hesitate to call for this, because it could unnecessarily slow the progress of good products, and would differentially penalise small business. I wonder if a better way forward might be to reinstate the tradition of a public regulator capable of doing their own independent testing of products including risk assessment testing, on a developer-pays basis, with accountability for their findings.

    Of course we’d also have to consider removing from the legislation the obligation of these regulators to “promote trade”. Their service should be exclusively to safety in my view.

  • “Marym”
    I think that my report makes clear my methodology and approach, so I’ll direct readers to that rather than repeat it here. I also explain why I chose the sequences I used. If you think I took too big a chunk for my comparison, then the answer is easy: tell me what sequences were actually used and re-run the analysis looking for any near 21 base pair matches or 7 base pair matches in the 3′ UTR.

    I hope that the sequence used has no matches to anything of importance in us or other animals we might wish to protect who may come into contact with the wheat. The questions here are:
    Were these exposure pathways identified in a formal risk assessment? If not, why not?
    If they were, what analysis was done to determine if the dsRNA (or secondaries) would not cause harm?
    Let’s evaluate what was done on a product intended to be eaten by volunteers.

    You seem to object to my asking these questions. Why shouldn’t I? Why don’t you or someone else put the matter to rest by showing the historical documents that demonstrate that a risk assessment on the dsRNA was done? Better yet, just show us the data that verified that there were no adverse effects of the dsRNA in the wheat.

    This line of posting reminds me very much of the VIOXX story. There too safety-oriented scientists called for specific testing of a potential adverse effect but the scientists were dismissed by the developer. These scientists saw what was a ‘speculative’ low level, statistically insignificant effect in a trial that was not designed to provide statistical confidence in the question of whether VIOXX was harmful to people with heart conditions. If only the simple testing for this effect had been done prior to commercialisation, rather than spending time avoiding the experiment through argumentation.

  • Jack,

    Could you clarify this: “my report on a risk assessment met the same or higher criteria for peer review that regulators and the industry use routinely”. I haven’t time to look back at the report right now and I’m not sure what you mean. Are you saying your report was peer-reviewed before you released it – ?

    (More about the sequence analysis later today if I can find time and am inclined to – trying to juggle balls here. My initial feelings are that your statements re the Cell Research paper look a bit too strong – just initial thoughts.)

  • CSIRO answered my request for the actual in-plant sequences. Their reply was longer, but in relation to the request they wrote

    “Information relating to the sequence of the transgene in individual transgenic events would normally only be requested by the regulator as part of the regulatory process for approval for commercial release of a specific transgenic event. Given that no decision has been taken to apply for regulatory approval for commercial release for any high amylose wheat GM line, and no decision has been taken to conduct any further field, animal or human trials, such information has not been requested by any of the regulatory agencies involved.”

    That is, I wasn’t given the in-plant sequences and so we can’t determine specific off-target effects arising from this wheat. Fair enough if CSIRO isn’t going forward with it, but our food regulators FSANZ have passed at least one other dsRNAi GM crop for food approval without any apparent evaluation of off-target effects. There needs to be some regulatory initative and adaptation, or at least some scientific reading in regard for the 22 million Aus + 4.4 million NZ’s for whom ?2 or 3 people at FSANZ make food safety decisions. http://www.madge.org.au/Docs/MR-110329-All-aboard-the-Hindenburg.pdf

  • Correction: “…so we can’t determine specific SITES FOR POTENTIAL off-target effects…”

  • Grant, I read that as a suggestion that regulators and industry weren’t peer reviewing at all – thus releasing the report to the public where it may then be peer reviewed was a higher standard of review. i.e. it hadn’t been peer reviewed prior to publication.

    I could be wrong in my reading of this however, an interesting point.

  • Jack, I started with a reply to your questions about when it is appropriate to communicate and when it isn’t. It got way out of hand so I put it here:
    http://www.3rdkingslandirregulars.net/2012/09/when-is-good-time-to-talk.html
    Short answer: there’s a bucket load of confusion out there already from commercial and special interest groups using science and the impression of science to advance agendas already, we should be communicating what we’re doing and then after review, communicate the results.

    I don’t think the imposition of costs for independent review for small companies stacks up either, given the cost of developing a new GMO in the first place (review cost should be proportionately small surely) and if there’s potential for harm, it has to be openly assessed whether its a large or small company.

  • Ok, so Jack won’t (or can’t) explain his unreasonable selection of the enormous sequence in Appendix 1. We’ll acknowledge that this enabled him to inflate the claims of matches to GBE.

    Appendix 2 is a bad file, and I had trouble opening it. I had to get a copy from someone else who was able to open it. So I’m missing pages. But I was able to note that the sequence used here was not the same as Appendix 1. Yet that’s not described anywhere. Why is this sequence different Jack? And what is this sequence please?

    What happens if you run the same BLAST parameters as you show for Appendix 2 with the sequence you use in Appendix 1?

  • To Marym:
    I find Jack’s report provides adequate coverage of methodology and assumptions. I would be more interested in knowing the answers to the questions Jack raised when he showed the plausibility of sequence matches. As Jack says in his report, the bioinformatics alone can neither prove that harm will result nor prove the product is safe, but it can support a call for testing. I agree. Where is the evidence that the risks were considered and/or tested? Answers to those questions will take us forward.

    Ossama A.El-Kawy, PhD
    Senior Scientist – Egyptian Atomic Energy Commission
    UNEP- GEF Regional Advisor on Cartagena Protocol

  • “Marym”
    As I posted before, the answers to your questions are in my report, but see below. Perhaps you could do us a favour and start answering some questions as well. Why haven’t you replied to Joanna’s comment to your anonymity? Peter, Grant, Joanna and I take responsibility for what we say. Why not you? Who are you? Who do you work for?
    Importantly, are you asking CSIRO for the actual sequences used? That information would get us much faster to an answer than ongoing speculation on what sequences they might or might not have used. What information have you seen on the unpublished risk assessments done by CSIRO?
    From my report-
    “First, the actual siRNA sequences were not available. Thus, I consider whether any siRNA sequences could have an effect, not whether all possible siRNAs would have an effect.
    Second, unintended secondary siRNAs that might be generated in planta or in humans cannot be anticipated but may well exist. For example, it was secondary dsRNAs that were the effective agents in establishing RNAi in insect pests who ate GM corn plants designed to produce primary dsRNA molecules (Baum et al., 2007), and it was pre-mature microRNA of rice plants modified by human cells that caused silencing of genes in human tissue culture cells (Zhang et al., 2012b).” I would add these references in addition for you
    Pak, J.; Fire, A. Distinct Populations of Primary and Secondary Effectors During RNAi in C. elegans. Science. 315:241-244; 2007
    Sijen, T.; Steiner, F.A.; Thijssen, K.L.; Plasterk, R.H.A. Secondary siRNAs result from unprimed RNA synthesis and form a distinct class. Science. 315:244-247; 2007.
    Since secondaries can arise in plants it remains in my view pertinent what similar sequences surround the SEI gene until we know 1: what the actual primary dsRNA was and 2: what the mechanism of silencing was (e.g., whether it was through TGS or cytoplasmic).
    “Third, bioinformatic tools are not definitive for predicting the effectiveness of siRNAs at causing an RNAi effect, particularly for ruling out an effect. As a biosafety scientist, I am interested in minimising type II errors (those that result in false negative identification) rather than minimising type I errors (those that result in a false positive identification). Any possible siRNA identified through bioinformatics techniques is a candidate for further testing, but bioinformatics is not a substitute for other kinds of testing.”
    “Absent for this analysis were the DNA sequences used by CSIRO to construct the siRNAs. This proprietary information is necessary to conduct a definitive bioinformatics analysis for risk assessment. To compensate for this, all possible known sequences from the named source genes as available in NCBI database were used.”
    “The results neither imply that all possible targets of interest have been identified, nor that all targets identified are certain to be silenced. For these final hypotheses to be tested, the actual sequences would be required. It would be incorrect to assume that if targets discussed below were not affected, that the constructs were safe for use. Likewise, it would be incorrect to conclude that sequence similarity between actual siRNAs and any targets below will necessarily cause the targets to be silenced.”
    “The SEI sequence used in this evaluation was originally submitted to GenBank by the CSIRO. It includes the coding sequence for SEI and a preceding pseudogene. Since I do not know what sequence was used by CSIRO, the entire submitted sequence was included in this analysis.”
    You can determine for yourself from appendix 2 what matches correspond in the human genome to the region of the full sequence CSIRO posted if that is your interest. My interest is in determining what analysis was actually done.

  • Jack,

    Regards, “Why haven’t you replied to Joanna’s comment to your anonymity?”

    Pseudonyms are accepted on-line and strictly-speaking your criticism could be taken to be ad hominem. It’s usually regarded that people’s arguments should rest on their words and should people want to use a pseudonym, that’s their personal call.

    One caveat I would add it that I personally (strongly) prefer people to disclose conflicts of interest. Similarly, if there might be one perceived, to clarify. This applies regardless of using real names or not. I wouldn’t mind knowing, for example, if Joanna has any relationship to your work on GMOs given she works in the same institution as you and in some respects her interests may overlap. (There’s nothing personal in that.)

    For what it’s worth, I know (of!) some people writing under pseudonyms who very clearly know their stuff well – it comes through from their writing.

    I haven’t time (yet) to return to the sequence analysis, but personally I can’t help wondering the entire report might have been better replaced with a simple, plain language, request for information. I’ll give you a heads-up, though – don’t count on my views on the sequence analysis done being favorable! (Friendly warning and all.)

    Just to repeat what I suggested in comments following Peter’s post:

    “I would have thought it clearer for the CIRB report to simply say that as a human gene that is identical, or very nearly so, to the plant SEI (and SEII) genes throughout [it’s length] (i.e. including the non-coding regions of the transcript) was not found, it can’t be called either way without knowing the dsRNA sequence.”

    (I wrote this by way of cutting to the chase and avoiding any conflict over the actual analysis done.)

  • Jack,

    Sorry but I don’t see your comment there as answering my question. You write generally about peer-review, but my question was if your review received any peer-review before it was released (or not, as the case may be).

    Note that isn’t anything to do with what the “best” approach to peer-review is, interesting—but different—question that might be, just a straight-forward yes/no question so that I might better understand how your report was prepared.

  • Hi Grant YES
    This is what I posted under Peter
    “All sides of this process have peer-review, Peter. What I think you are referring to is blind peer-review with an intermediary, what we normally call an editor if the writing is for a journal.
    We used the same peer-review procedure for the INBI report as we have seen the regulators use. They seek expert critical comment but serve as their own editor. Documents and decisions produced by EPA, OGTR, and FSANZ follow this procedure too.”
    My report used experts from the field before I released it to the commissioned party. The reviewers are listed in my report.

  • “The reviewers are listed in my report.”

    I’ve skimmed the review, particularly the top, bottom and footnotes, key-word searched for ‘review’ (no match) and I don’t see any reviewers listed. Where are we to look? Are these in some supplementary material?

    I’m a bit confused, The title page opens “An expert opinion of” – i.e. one person’s view. Are you talking about the same review or some other?

  • Sorry, footnote 11
    And yes, that is my report with the title page “An expert opinion…”

  • Hope you don’t mind the poke—imagine me as a grumpy peer-reviewer!—but is this mostly informal comment from colleagues rather than independent “peer-review” from “experts from the field”? (Note emphasis.)

    In particular, the second and third reviewers look to be past or present collaborators or lab members and thus have conflicts of interest (PubMed shows them to be authors on papers Jack is an author, etc., e.g. http://www.ncbi.nlm.nih.gov/pubmed/21624662 http://www.ncbi.nlm.nih.gov/pubmed/22806010).

  • OK, so it’s two links that trips the moderation filter on this blog. Here’s my comment currently held up in moderation without links:

    Hope you don’t mind the poke—imagine me as a grumpy peer-reviewer!—but is this mostly informal comment from colleagues rather than independent “peer-review” from “experts from the field”? (Note emphasis.)

    In particular, the second and third reviewers look to be past or present collaborators or lab members and thus have conflicts of interest (PubMed shows them to be authors on papers Jack is an author, etc. [links to two examples, one for each reviewer, omitted.])

  • Grant,
    Your comment about me illustrates why anonymous or pseudonymous postings are a problem. In these Googlous times, posting under my real name enabled you, indeed invited you, to find out my institutional affiliations if you were so inclined. Try googling “Mary”.

    I do have an affiliation with INBI (not exactly surprising, given that I work at Canterbury and have relevant academic interests), but I receive no salary or other economic benefit from it. I was not involved in the research in any way. In the interest of full disclosure, I can also say that Jack is a friend. Note that at this point I have gone far beyond anything you or any other poster have done to clarify your relation to the various parties to this debate.

    More relevant to the substance of my comments is my area of expertise. To quote my (publicly available) research profile: ‘My research interests lie at the intersection of technoscience and democracy. More specifically, my research focuses on: the social and political implications of science and technology, the role of democratic publics in relation to science and technology, government consultation strategies on technoscience-related issues, and the interaction between all of the above and neoliberalism.’ I have also researched regulatory policy as well as the nature and quality of debate on GMOs and their regulation.

    Moreover, as an ordinary (if educated) citizen and consumer, I have concerns about the chilling effect of concerted personal attacks on any researchers who displease certain powerful interests. I know enough not to want to have to trust my and others’ well-being to those who have strong economic incentives not to find problems if they do exist. There seems to be a willed naivete about this among many commentators and some regulators: indeed, it is built into regulatory systems that rely heavily on developers’ own safety-testing..

    If I didn’t know Jack, I may not have been aware of the Sciblogs discussion, in which case I obviously would not have posted.

    But I struggle to see how that constitutes a ‘conflict of interest’ when it comes to the content of my posts, or how anything I actually said can be seen to have less value as a result of the fact that I know Jack. Does my knowing Jack mean that ‘Mary’ did not in fact resort to ad hominem argument (regardless of whether ‘Mary’ him-, her- or it-self has a conflict of interest, which we of course cannot begin to determine because of the anonym/pseudonym)?.

    So, it seems to me inconsistent of you to approve of pseudonymous postings while at the same time warning of the effects of conflict of interest. Wouldn’t those with the strongest conflicts of interest be among the most likely to post anonymously? In which case, they are hardly going to disclose those conflicts in their posts, are they?

  • Jack–you and Joanna can create a list for me of associations that would disqualify my analysis, and I’ll answer them. Right after you tell me why you switched sequences in Appendix 2, which you did not describe. I am not associated with CSIRO, or with any Ag organizations, or any regulatory agencies. But I have no idea what else in your mind would create a problem. I didn’t get paid for my analysis–I’m doing that for free. Did you?

    Now, despite Jack not telling everyone that he changed sequences for Appendix 2, I think I know what the sequence is. It took some work, because of the crappiness of the file. But I think it’s just the gene segment. Jack can confirm this quickly, surely.

    What does that tell us?

    Jack deliberately choose to *not* use just the gene part when he wanted to inflate the claims, as we know he could have chosen it and knew how to do so.

    This switcheroo might be referred to as stacking the deck.

    And why does it matter which part you pick? Because the claims nearly all evaporate if just the gene is used. The claims may evaporate still further if only part of the gene is used as CSIRO indicated on the OGTR page where Jack says he got the sequence information.

    If this construct is similar to others successfully used by CSIRO on a related project, we could make some predictions about which pieces of SBE1 are likely to be attempted. In this paper on SBEIIa, a construct made of exons 1-3 and intron 3 worked very nicely (http://www.pnas.org/content/103/10/3546.long). If we used a similar strategy for SBE1, and take exons 1,2,3 and the intron after 3, do we have any concerning matches to GBE? And since I don’t know how they count introns (if they include one before the ATG for the starting methionine as one) I’ll even take both the intron prior to exon 3 and the one after exon 3. http://screencast.com/t/pOvqvLRpf I’ll even add a few nucleotides just to get to even line end numbers so people could easily reproduce this.

    If we use this sequence, there are no significant matches to GBE1. None. Zip. Nada. Zilch. Zero. http://screencast.com/t/lLtA6gDN82z The claim of liver disease and death of children by age 5 as a result of this is bogus.

    If we use this same sequence on the G+T database that Jack used, not a single transcript match appears.

    So what we have is inflated claims based on unlikely matches underlying this whole circus. SafeFood and their hired guns have made people less informed and more fearful as a result of this flawed analysis.

    You may pressure the regulatory agencies all you want for whatever analysis you want them to do. I don’t care if you demand tests for chemtrails and Morgellons while you are at it. But it is despicable to use inflated claims to generate misinformation and widespread public fear to do so.

  • [Will someone please shake my comment out of moderation? It has multiple links because I sourced my claims.]

  • Just to clarify on a point made in my previous post:

    The comments of mine that Grant is referring to (at http://sciblogs.co.nz/southern-genes/2012/09/12/does-eating-transgenic-wheat-destroy-your-liver/) do not ask the reader to trust me or my judgement or my claimed expertise. As my comments analyse comments made in the same discussion, the reader can check for him- or herself the reasonableness and accuracy of my comments simply by scrolling up and re-reading the comments I am referring to. The same is not true of others, particularly “Mary”, whose comments are full of personal judgements that cannot be easily assessed by the reader. When we are asked to trust someone’s judgement, it is particularly important to know whether that person has a vested interest in the matter. This makes it all the more puzzling, Grant, that you are concerned about my possible conflict of interest, but not “Mary’s”.

  • joannagoven,

    I’m not taking sides here, just trying to clarify that pointing at the use pseudonyms in and of itself isn’t really sound.

    This is a sideline here and one I don’t think is helpful.

    Just because someone is writing using a pseudonym doesn’t make their words wrong or lesser. Not disclosing COIs might still be an issue, however – which is why I brought it up – but these also applies to those using real names. (COI – conflict of interest.)

    This use of pseudonyms is very widely discussed and explored amongst science communication people on-line and I read many discussions of this over the past few years. Suffice to say, that if someone uses a pseudonym (or not) should not on it’s own be a reason to diminish what they say.

    Coming now to your comment, your last sentence reads, “This makes it all the more puzzling, Grant, that you are concerned about my possible conflict of interest, but not “Mary’s”.”

    This misrepresents what I wrote, perhaps inadvertently, but it’s not right all the same.

    If you re-read what I wrote in it’s full context you will see it was given as just mentioning you as an example to illustrate that the issue of COIs “applies regardless of using real names or not”. There is no ‘being concerned’ about a COI by you and not not Mary in what I wrote – that would be implying meanings on my words.

    Let me quote you the full passage of what I wrote again:

    “One caveat [regards pseudonyms] I would add [is] that I personally (strongly) prefer people to disclose conflicts of interest. Similarly, if there might be one perceived, to clarify. This applies regardless of using real names or not. I wouldn’t mind knowing, for example, if Joanna has any relationship to your [Jack’s] work on GMOs given she works in the same institution as you and in some respects her interests may overlap. (There’s nothing personal in that.)”

    I would add that COIs are not (just) about the accuracy of statements per se they are about wider settings, context. Context can matter.

    Regards, “As my comments analyse comments made in the same discussion, the reader can check for him- or herself the reasonableness and accuracy of my comments simply by scrolling up and re-reading the comments I am referring to. The same is not true of others, particularly “Mary”, whose comments are full of personal judgements that cannot be easily assessed by the reader.”

    With all respect, readers can also, to paraphrase you in active tense, surely readers can ‘scroll back up and re-read the comments’ what Mary wrote too?

    Regards “personal judgements” – you’re entitled to your perceptions and I’d have to look back to re-examine what was written and haven’t time, but my recollection is that while marym’s comments may be more to-the-point than might appeal to you, I haven’t noted any ‘personal’ stuff myself.

  • Grant,

    I don’t think you have dealt with your own inconsistency. You requote yourself as saying that you “wouldn’t mind knowing” what my relationship is to Jack’s research. But you’ve expressed no desire to know what “Mary’s” relationship is to the kinds of GM development that may be affected by the research. This still looks like a very one-sided curiosity to me.

    As I noted in an earlier comment, posting under my real name enabled you, indeed invited you, to find out my institutional affiliations if you were so inclined. It is impossible to do the same with a pseudonym. (Try googling “Mary”.) So you’ve demonstrated why those with the most serious conflicts of interest may well post pseudonymously.

    So: using a pseudonym rather than identifying oneself makes it virtually impossible for anyone to discover if there is an undisclosed COI. It would be good to acknowledge that.

    I didn’t say that COIs are (just) about the accuracy of statements per se, so I don’t know what you are referring to there. Although I note that you have said, in defense of pseudonyms, that “people’s arguments should rest on their words”. Again, this seems awfully inconsistent to me.

    With regard to your comment “surely readers can ‘scroll back up and re-read the comments’ what [that?] Mary wrote too?”–it is in fact “Mary’s” comments I am referring to. So there may be a misunderstanding here, in which case I clarify below:
    As my comments analyse [“Mary’s”] comments made in the same discussion, the reader can check for him- or herself the reasonableness and accuracy of my comments simply by scrolling up and re-reading the comments [by “Mary”] I am referring to.

    If on the other hand you mean that “Mary’s” comments ALSO do not (implicitly) ask the reader to trust her, her judgement, or her claimed expertise, and that the reader can similarly check the veracity and reasonableness of “Mary’s” comments by reading other material on the same page, that is incorrect. For example, “This is undoubtedly a case of yelling ‘fire’ in a crowded theater. It is science-by-press-release, refuge of cranks.” Where on the page can that be verified?

    And, with all respect, I think you have to try pretty hard not to have noticed personal judgements in “Mary’s” comments. The one I quoted two sentences ago is one example; others are:
    – “incredibly irresponsible fear-mongering”
    – “a baseless, speculative case based on a terrible analysis”
    – “a foul strategy”
    – “a fear-based method that should repulse anyone who values the public discourse”
    – “It’s shameful how you misused the fears of people who don’t understand the science.”
    Not personal judgements?

  • joannagoven,

    Hey, easy! Just a thought: try assuming someone means well and is being honest first. Wouldn’t that be better? (Or at least nicer.) You seem to have jumped to a bad reading of my words – you’re implying that my polite explanation was a lie. Not nice. I was straight-forward. I mean this as kindly as I can: any ‘reading of meanings’ into it are your own!

    (I could say a lot worse here. For what’s it worth I left my reply open and didn’t accuse you of anything so that you might have opportunity apologise for your mistake.)

    That out of the way, your other points.

    You wrote that “It would be good to acknowledge that.” – I am the one who raised that point! :-)

    Regards, “I didn’t say that COIs are (just) about the accuracy of statements per se, so I don’t know what you are referring to there. Although I note that you have said, in defense of pseudonyms, that “people’s arguments should rest on their words”. Again, this seems awfully inconsistent to me.”

    Re the first sentence – I didn’t say you did. My sentence starts “I would add that” – it’s pointing out it’s additional thoughts to my previous remarks on pseudonyms that I’d just quoted. I’m sorry, but I don’t follow what you’re trying to say with your last two sentences?

    “With regard to your comment” – I meant the second. You’re trying too hard, I think. You emphasis ‘also’ as distinguishing your two readings – look back and you’ll see I used that word too.

    Re “personal judgements” & your quotes of Mary’s words – aren’t your, my and everyone else’s judgements are ‘personal’ in that sense too? She’s entitled to her judgements, just as you are entitled to your own. (I’m not taking sides here.)

    I can’t recall anything ‘personal’ in the sense of “‘personal’ stuff” (my words). See the difference?

    Seriously though, why shouldn’t she criticise the approach taken if that’s her view? It’s a criticism, you don’t have to like it! Wouldn’t it be better to deal with the points raised, instead? – for example try show that it’s not fear-mongering, if that’s your stance.

  • The mental gymnastics of those attempting to justify this media release is very revealing. Just this week there was another orchestrated release of a study by those with an anti-GM agenda (Seralini). When scientific convention is repeatedly eschewed by scientists on one side of the “debate” (for want of a better word) in a manner that clearly poisons the well one can only conclude that it is an intentional tactic to do so.

  • Sorry, Grant, you’ll have to explain where I’m assuming that you are lying. I think you might be the one jumping to a bad, not-nice reading.

    I’m not sure what you mean by “a lot worse”. And what is my mistake that I am meant to be apologising for?

    In case it is relevant: I actually responded to your initial comment with a long post that has been caught up in the moderator filter for a couple of days (fair enough, moderators should have weekends, too). The comment of mine that begins “Just to clarify” is actually a later addendum to that longer comment. You might want to read that before continuing in the direction you seem to be going with those rather veiled comments.

    What is it that I am trying too hard to do? I think you’ve misunderstood what I am saying. Emphasising ‘also’ was for clarity; it was not an accusation.

    I assumed that ‘personal stuff’ meant ‘personal judgements’ because of the context in which it appeared, namely:

    ‘Regards “personal judgements” – you’re entitled to your perceptions and I’d have to look back to re-examine what was written and haven’t time, but my recollection is that while marym’s comments may be more to-the-point than might appeal to you, I haven’t noted any ‘personal’ stuff myself.’

    It seems a fair inference.

    My point, if you go back and look at it, was not that a person should not express criticism. My point was that it is precisely when a commenter expresses judgements that go beyond what can be readily verified that COI is the most relevant. In contrast, when the claims can be readily verified, COI revelation doesn’t add much.

  • joannagoven,

    “I think you might be the one jumping to a bad, not-nice reading.”

    Please, that is silly. Why are you persisting at playing tit-for-tat?? Surely it’s clear I’m not interested in that?

    I wrote: “I was straight-forward. I mean this as kindly as I can: any ‘reading of meanings’ into it are your own!”

    A small tip: Some of what I’ve written isn’t fully fleshed out because I wrote some as leads with the hope you’d follow them and see for yourself, in turn in the hope that you’d realise for yourself that you’re making a mistake criticising me like this. I was doing that for your sake.

    You erred in trying to ‘read into’ my words some thing about not being concerned with possible COIs from Mary. Can you not simply accept that you erred? (It’s not quite the case here but if it gets you to stop (!), try applying ‘a lack of evidence is not evidence of a lack’.)

    Since then you’ve gone and read all sorts of other nonsense into what I’ve written. I’m trying to be patient but I’m increasingly wondering why, or if, I should!

    “I’m not sure what you mean by “a lot worse”.”

    Please, that’s silly.

    “And what is my mistake that I am meant to be apologising for?”

    Ditto. But never mind. I guess I’m not going to get an apology :-(

    “In case it is relevant: I actually responded to your initial comment with a long post that has been caught up in the moderator filter for a couple of days (fair enough, moderators should have weekends, too). The comment of mine that begins “Just to clarify” is actually a later addendum to that longer comment.”

    Thank you for clarifying. Is this “initial comment” of mine that you refer to in comments to this post, or to Peter’s earlier post? Immediately after writing “Just to clarify on a point made in my previous post:”, you wrote that “The comments of mine that Grant is referring to [URL of previous blog post by Peter]”. (Naturally, I read you as you referring to your last comment on Peter’s blog.)

    “You might want to read that before continuing in the direction you seem to be going with those rather veiled comments.”

    None of my comments are ‘rather veiled’ (with it’s implication that I’m insinuating things). As I wrote “I was straight-forward.” Suggesting that I am ‘continuing in a direction’ is at best unhelpful. If there is a ‘direction’ my recent comments have been going in, it is trying to get you to stop making out things my words haven’t said!

    “What is it that I am trying too hard to do?”

    You’re trying too hard to find “bad reading of my words”, as I wrote earlier. I gave the opening advice (“Just a thought: try …”) to try encourage you to slow down and see I’m not doing the things you are making me out to for yourself.

    “I think you’ve misunderstood what I am saying. Emphasising ‘also’ was for clarity; it was not an accusation.”

    I did not misunderstand your emphasis was to distinguish the two readings you offered – in fact, I wrote that myself: “You emphasis[e] ‘also’ as distinguishing your two readings”

    I certainly didn’t make it out as an accusation – but you, not me, just have. What you have written right there is an example of what I’m talking about. Goodness knows where you get an accusation from “You emphasis[e] ‘also’ as distinguishing your two readings – look back and you’ll see I used that word too.” – it was a gentle hint I was on track and you’d see it if you read back.

    As best as I can tell you have gotten yourself all wound up over my using you in an example and are ‘seeing’ all sorts of nonsense that isn’t there.

    “It seems a fair inference.”

    Sorry, but this brings me back to: Please, that’s silly. I’ve already clarified, there’s no need for tit-for-tat.

    ”My point was that it is precisely when a commenter expresses judgements that go beyond what can be readily verified that COI is the most relevant.”

    Sorry, but I’ll stand opposed. To be frank, it seems that you just don’t like her judgements and are fairly determined to find a way to dismiss them. To repeat my suggestion: “Wouldn’t it be better to deal with the points raised, instead?”

  • Grant,
    The questions you’ve dismissed as “silly” were genuine questions. The comments you’ve dismissed as “tit-for-tat” were genuine attempts to clarify what I saw as your misunderstandings of what I was trying to say. Your dismissals, whether you intend it or not, effectively shut down the conversation. Questions dismissed as “silly” and comments dismissed as “tit-for-tat” apparently need no response. (The fact is that I didn’t accuse you of lying or imply you had lied. I tried to get you to explain what made you think I did.) And there is little point in the person whose questions and comments are dismissed, or persistently misconstrued, to continue trying to take part in the conversation.

  • @joannagoven: just to be clear–if I have no COI, no employer or agency conflicts, no payment for analysis, no friendships or professional relationships that affect my position, no relationship to activist organizations, then my analysis is acceptable?

    And if someone was paid for their analysis, theirs would be tainted?

    This just keeps getting funnier.

  • I don’t think I see your criteria for accepting someone’s analysis there @joannagoven. You’ll have to be more explicit. And a list would help, as I asked above.

    Which I said I’ll answer as soon as Jack tells us all why he switched sequences.

  • joannagoven,

    Yes, I tried to close it down, but it wasn’t for the reason you make out. (Ironically that has your response misrepresenting me again.)

    I did not ‘dismiss’ your words – that’s characterising what I’ve written, and badly. Those points of your’s that I called silly are silly because in writing them you’re perpetuating tit-for-tat that you ought to have closed off yourself earlier. That was the point I was making in saying I think they’re silly. I even wrote that explicitly.

    Go back and read your words. (You seem to focus on my words without looking at your own.) You objected to my using you in an example, but misrepresented me in describing what it said. No big deal, it happens. I wasn’t especially bothered by it. Go back and read what I wrote – it was very polite and do think I explained it clearly enough. You might have simply accepted that. Instead you proceeded to “read meanings” into my reply, which you then keep doing in circular fashion. Trying to claim the high ground as a conclusion is not right nor fair.

    So, yes, I’d like to see it end. I don’t enjoy that I tried politely to put you right only for you to repeatedly ‘read meanings’ into what I write in such a negative way. but I didn’t write the way you describe.

    I have little time to address the sequence analysis (never mind read the intervening comments) at the moment, but may try later in the week. (I see marym’s earlier comment regards the sequence analysis has now come through moderation.) That’s me being hopeful…! If I do I may prefer a blog post to give it a clean start.

  • Grant,
    At this point I am happy to let the interested reader (if there are any) draw his or her own conclusions about what is a reasonable interpretation of what has been written.

  • I think the key thing is really to look hard at Jack’s analysis and claims–you know, to separate the wheat from the chaff as it were. Since I can’t seem to find out if people really have looked at the sequence analysis, I’ll do so in a series of videos. That way everyone can see what was done. And I hope I’ll also provide enough information for people to do the analysis themselves, based on the parameters Jack provided.

    So here’s the first one. If Jack, or any of his reviewers, or other Safe Foods consultants can help me to understand why I don’t see the same thing in Appendix 1 I’d love to know. Maybe NCBI BLAST works differently from your side of the planet.

    https://vimeo.com/50146826

    I’ve tried to reproduce the analysis based on what was in the documents. If there are other things I can’t see, Jack will have to provide the details or an explanation.

  • @Jack Heinemann

    Any chance you will respond to @marym’s last post before the multiple posts by joannagoven and Grant Jacobs ?

    I feel it is kind of a bad point in the conversation to stop responding.
    It might give the wrong (or right) impression to the casual reader.
    The points made by marym seem valid.

    F.Y

  • In this next video, we have a good look at the very-very-very long sequence in the wheat record that forms the basis for the next comparison. https://vimeo.com/50306509

    You have to understand this record’s structure to understand the subsequent issues that will arise.

  • marym,

    Great work, you’ve gone to a lot of effort! Now let’s see if I can find time to see what you got up to.

    Just a heads-up for readers – you’ll want to track back to marym’s earlier comments – try using ctrl-F (Mac users: cmd-F) to search the page for marym’s comment.

  • Here’s the next installment: wherein I start to do some forensic bioinformatics to try to figure out what was done to create Appendix 1, since the parameters provided don’t show it.

    https://vimeo.com/50440285

    To do this yourself, you need the 2 sequence record links I provided above (human and wheat). You have to change the BLAST settings at NCBI as I illustrate in the movie.

    In the next movie we’ll explore that result in more detail. There’s another deliberate change you have to make away from the default parameters to get more hits, and I will show that.

  • “Hundreds of researchers from 32 institutes around the world collaborated on the immense effort to decipher the hidden messages within the 98 per cent of the human genome without any genes and was thought, therefore, to have no function.

    They have concluded in a series of 30 research papers published simultaneously today, in Nature, Science and other journals, that this so-called junk DNA is in fact an elaborate patchwork of regulatory sequences that act as a huge operating system for controlling the genome.”

    from: http://www.independent.co.uk/news/science/scientists-debunk-junk-dna-theory-to-reveal-vast-majority-of-human-genes-perform-a-vital-function-8106777.html

    Could this have an effect on what science believes might or might not have an effect on our health ?
    What I am asking is whether if Dr. Heinemann using the whole sequence instead of just the gene was not such a bad idea after all ?
    What exactly is incorporated into the plant ? Only the genes ? If not, could the rest of the sequence also have effects we can’t predict yet ?

    Thanks for helping me understand.

  • effwhy (aka F.Y at Respectful Insolence, if effwhy’s previous sign-off is anything to go by),

    It’s already known this RNA regulates genes in plants – that’s why they’re using it in the first place. As for effects in humans, as opposed to plants, there’s a lot more to it than just pointing at ENCODE results. In any event, you’d want to check the claims in Heinemann’s report are sound first.

    I wrote earlier that whatever the case is, it’ll come back to basic testing that it‘s safe to eat (something I also told you at RI). I also wrote earlier that the report might have been better replaced with a simple request for information.

    With all respect, as I and others at RI have already told you many times, you can play ‘what if’ endlessly and meaninglessly – even after a thing is tested and shown to be safe. (Anti-vaccine and ‘alternative remedy’ advocacy groups do this endlessly, for example.) What’s needed is for objections to be meaningful – notice we’re back at checking the claims.

    Off-topic: re ‘junk DNA’ and ‘that’ 80% figure, you ought to also read the many articles explaining the media coverage re ‘junk DNA’ has issues. (I have an article in draft covering my thoughts on this, but would like to get two lead-up articles about ENCODE out first if I can.) Bottom line for you is that the activity in that 80% may or may not be used in any productive way by the cell. There is a wider philosophical issue, but all of this is off-topic here.

  • Yes, I am the same F.Y from RI. This site didn’t allow me to use the same sign in name (only lowercase and no special characters like the .), I had to improvise.

    Thank you for replying, though I am not sure you answered my questions.

    Anyway, how do you determine whether it is safe to eat ? Over what kind of time-period ? You say “it’ll come back to”, I don’t suppose you mean it hasn’t been done yet, right ?

  • The main points emerging from this thread, as I read them, are I. the issue of the many different procedures that different people call peer-review; II. what sequences should have been used; III. and what the nature of the risk testing should be.

    I. Following from Grant, my answer remains the same. The peer-review standard used by developers and the regulators is no different to the standard I used. We did not use anonymous – or the vague criteria of independent as I think you mean the term. Likewise, they (regulators, developers) select the reviewers and serve as their own editors. If you believe different standards should apply to how food safety is assured, great!, so do I. This system has been in place now for decades. Perhaps you should be writing to the ministries to correct this system. Meanwhile, what you have not done with this argument is shown that the food is safe or that this risk pathway had been considered.

    II. The sequences. I haven’t time to watch utube videos but I doubt that matters much. A. Nothing posted here by ‘marym’ or anyone else has proven that the risk assessment was done. Why not ask for the risk assessment? Talk about the BLAST parameters as you wish since the report is an open public document. Meanwhile, I will remain focused on what matters to most people and that is the question of whether the statutory requirement to conduct a proper risk assessment has been met.
    B. There is a large and credible body of research, some referenced in my report and others in my postings above, that show that the primary siRNA can be the cause of secondary siRNAs. This is not “woolly” or contested by those in the field. Therefore, a proper risk assessment in my view would be able to capture any potential adverse effect that arose from secondary siRNAs generated in the plant or in anything that potentially eats the plant. Hence, sequences beyond those of the ‘coding’ region are relevant. It may also be that the primary siRNA comes from sequences in the pseudogene if those sequences have a sufficient number of matches. I don’t know – and it is not for me to make up new assumptions about – what was used. Something was used, what was it? How was it tested?
    C. With RNAi, it isn’t about the overall similarity of genes. It is about how many matches form between the guide RNA and the mRNA. There are matches, end of story. BLAST is not designed to find potential siRNA binding sites. Thus, one has to work a bit harder with BLAST. Even though many others including myself do use BLAST for first approximations, all of us have acknowledged that BLAST cannot find all matches and others have built specialist tools to help design siRNAs. [This is all explained and referenced in the report.] Here is the critical point: BLAST does not overestimate the number of potential matches, it underestimates them. Until we have actual sequences, I see no value in conducting additional searches on the same reference sequence. It will not remove the plausibility of matches and it will only potentially increase the number of discovered matches.
    The argument about the safety of this GM wheat will only be able to advance when the actual population of siRNAs generated in the wheat are described and testing is done.
    III. Again, bioinformatics only establishes plausibility. As I have said, and Grant echoes, the definitive risk assessment is to test whether there is an effect. I have outlined a series of experiments in the report that I believe are capable of doing that.
    Myself and others in contact with regulators have called for these experiments, or equally valid alternatives, for years and these requests have been either ignored or refused. These refusals were not made on the basis of independent peer-reviewed evidence that the exposure pathways did not exist, that the dsRNA would not be taken up or on ANY peer-reviewed evidence on the GM plants being evaluated, but only on the assumptions of the regulator. What surprises me is how comfortable some commentators in this thread are with that.

  • Hi Jack,

    Some of your statements, in my opinion, over-reach in places e.g. writing ‘proved’ when citing the Cell Research paper. Similarly, I was surprised to read your claim that your report was ‘peer reviewed’, as to any scientist that implies independent peer review and hence a formal process. No offence, but I think you’d have been better to simply say it’s your opinion as a scientist. The statement in the report is fine, it says that some people commented on the draft. I have no qualms with that.

    You comment that “If you believe different standards should apply to how food safety is assured, great!, so do I.” (Bear in mind I’m not quite sure who ‘you’ refers to here – you’re nominally are writing to everyone, but then you refer to me earlier in the passage.) Speaking for myself, then, I did not write implying that the regulators should change their process, I made no reference to their processes. I was pointing out that the concerns raised in your report are hypothetical.

    Regards “Meanwhile, what you have not done with this argument is shown that the food is safe or that this risk pathway had been considered.” Some might just be focused on your report – and why not?

    “I haven’t time to watch utube videos but I doubt that matters much.” – they’re only a few minutes long 😉

    “Talk about the BLAST parameters as you wish since the report is an open public document. Meanwhile, I will remain focused on what matters to most people and that is the question of whether the statutory requirement to conduct a proper risk assessment has been met.” Personally I wouldn’t brush aside criticism of your report. That’s the price of writing in public 😉 It’s the same as when I blog anything for that matter.

    “Here is the critical point: BLAST does not overestimate the number of potential matches, it underestimates them. Until we have actual sequences, I see no value in conducting additional searches on the same reference sequence. It will not remove the plausibility of matches and it will only potentially increase the number of discovered matches.” Saying that BLAST underestimates might be true if you are using a ‘proper’ reference sequence, but not (necessarily) if the search is inappropriate. As one (overly) simple example, including in the reference sequence sequences that are not part of the dsRNA used in the in vivo construct may draw false positives (overestimating for these).

    “What surprises me is how comfortable some commentators in this thread are with that.” Some may simply be looking at your report in and of itself and nothing else – i.e. they haven’t said anything either way on the regulatory process. (Count me as one.)

    I would more to say about levels of risk (it’s not reasonable nor practical to ask for more than some level of risk) and the VIOXX example (at first brush it looks to me it only works in hindsight) but I have other things to do. That’s life.

  • My focus is definitely the analysis provided by Jack which caused the inflated claims by his team. This subsequently lead to public misinformation and fear in an incredibly irresponsible manner.

    Jack–can you at least answer why the Appendix 1 document parameters don’t match the data you show? I can keep explaining why I think it was done, but you could clear it all up quickly for us.

    I can understand why you want to divert attention from that, but let’s focus on your claims right now.

  • “Marym”

    Why do you wish to deflect attention from the absence of a published risk assessment on a product intended for consumption by human volunteers? A risk assessment that we can all evaluate? Let’s focus on that right now. It does seem curious to me that this same interest in bioinformatics is not equally focused on the actual product that people might eat.

    I’ve responded multiple times to your requests. Perhaps you can now supply peer-reviewed information to verify how the risk assessment was done and how it has excluded off target effects.

  • You don’t seem to understand the issue Jack. My problem is with your illegitimate claims.

    And why would I care what you claim about what regulators do if your science and data is deceptive? If you are willing to lie with data, why wouldn’t you lie about other stuff? Why should anyone believe you if your standards are thus?

    Jack’s step 1: make wild claims that he won’t detail, or will actively misrepresent. .
    Jack’s step 2: point fingers elsewhere.

    I’m still working on Step 1 Jack. Let’s get through that and then we can look at the rest, ok?

  • Good news, a long weekend here, so I’ll have time to get back to this analysis.

    In this video we look at the BLAST results in more detail to attempt to replicate Jack’s analysis, and re-examine the sequence used to see if the claims hold up.

    https://vimeo.com/50889687

  • In this video we look at how likely it was that the 25,000 nucleotide sequence was used for the CSIRO construct. We examine the OGTR page, we look at a similar project, and we see that it is entirely possible that there are no matches of concern.

    https://vimeo.com/50897487

  • In this video we start to look at Appendix 2. We see that Jack changed sequences without disclosing what that sequence was, or why he switched.

    But we also learn that here Jack does know how to obtain and use just the “gene” part. Why he didn’t do this in Appendix 1 is still unanswered.

    https://vimeo.com/50904125

  • In this video I try to recreated the analysis done for Appendix 2, using the sequence that Jack switched to. You can try to reproduce this yourself with the details from the movie.

    https://vimeo.com/50929940

    However, the Appendix 2 document was damaged, and some of the pages don’t appear properly for me. So I’ll need Jack to describe what the specific parameters were that led to the result he shows.

    Jack: what are the parameter settings you used for the BLAST in Appendix 2?

    I’m giving you a chance to respond to all the issues that are coming up before I assemble a full post on this story.

  • Ok, it’s been over a week now. Unresponsive. Duly noted. I’ll let you know when I have the full post assembled and available.

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