Does eating transgenic wheat destroy your liver?

By Peter Dearden 12/09/2012

Peter K. Dearden

Today saw some discussion in the press about a statement by Canterbury University’s Prof Jack Heinemann,  Prof Judy Carmen (Flinders University) and Prof Michael Antoniou (King’s College, London), around the risks of a new transgenic wheat variety being assessed for release by CSIRO in Australia. These statements released by the Safe Food Foundation, provide an opinion on the safety of this new wheat variety, and are interesting reading.

The new wheat variety aims to increase the amount of resistant starch, making this starch less easy to digest with apparent health benefits for the consumer. To make this variety, CSIRO has used a transgene that suppresses two plant genes, genes that make easy-to-digest starch. They have utilized a technique called RNA interference to do this. RNA interference is a modern technique whereby a small piece of double stranded RNA is made that is the same sequence as a gene you want to turn off. Now, RNA, the molecule that takes the sequence of DNA and is translated into protein, is normally single stranded. Double stranded RNA appears to be a warning signal for many organisms because they generate a response to it that causes all RNA of the same sequence to be degraded, and DNA with the same sequence to be silenced. Thus because genes are first transcribed into  RNA before making protein, double stranded RNA causes any gene with the same sequence to be turned off.  In this case, a small bit of DNA that, when transcribed, makes double stranded RNA of the same sequence of the two enzymes involved in making easy-to-digest starch, has been inserted in the plant genome. When active, these make double stranded RNA and thus turn off these genes, presumably making the starch produced by the plant more resistant to digestion.

Clever huh!

Now plants, and animals, also use small bits of double stranded RNA to regulate our own genes. The machinery that recognizes double stranded RNA is present in our cells, and used by them to do important things. A recent paper also shows that some of these small double stranded RNAs from plants can be found in Humans who have eaten those plants, and that they might cause some silencing of human genes. So it is possible that the bits of RNA that CSIRO has put into the plants to silence the making of digestable starch, might end up in people eating that plant. Now this normally would be no problem, because the process is sequence-specific, only genes with the same sequence as the plant gene being silenced in our own genome might be affected. Unlikely you might think? Think again. Organisms share a great deal of genetic information, and we do have a gene, called GBE, in our genome with similarity to the plant genes (SEI and SEII) being targeted. GBE encodes a protein that makes branched glycogen molecules. Glycogen is our way of storing carbohydrates, and GBE makes branched versions. Humans unable to make branched glycogen have a disease called Glycogen Storage Disease IV, that leads to damage in the liver, as pointed out by Prof. Judy Carmen.

So is it possible that this new variety of wheat, by making bits of RNA to silence the plant genes, might silence the human GBE gene in our livers leading to Glycogen Storage Disease IV? Possible, but, in my opinion, easy to avoid and unlikely

Let’s take this in bits….

The key is sequence similarity. The human gene GBE has similarity to the plant genes SEI and SEII, but this is limited and not across the whole sequence. The similarity is probably in the active site of the enzyme, which is presumably doing a similar job. The important thing is not protein similarity though, but DNA sequence similarity, which is low. To avoid the problem, however, all you need to do is make the bits of RNA you are expressing in the plant, from regions of the plant genes that ARE NOT similar to the Human gene. Simple. Has this been done? Who knows? CSIRO have not released to the public the sequences that have been used to silence the plant genes (I assume the regulators have seen them).

Certainly if I were doing this, I would target a region of RNA at the end of the gene, which doesn’t encode protein, and evolves fast. This region, named the 3′ untranslated region, is not similar between plants and mammals, and is the natural target of the double stranded RNA system, so likely to be a safe and effective method of silencing.

Prof. Heinemann also suggests that the manner in which the double stranded RNA is made in the plant could produce molecules with unexpected targets, again causing problems in humans. This seems less likely. It is relatively easy, with modern sequencing techniques, and good control of transgenesis, to make sure that these unexpected molecules do not occur, or occur in such low amounts that they are unlikely to have an effect.

So while Prof Heinemann and friends do raise important points I think it unlikely that this crop will cause the disease.  It is important to say, however, that CSIRO needs to be sure that they aren’t using sequences found in humans, and need to disclose that. Part of the problem here is the secrecy around intellectual property. I cannot judge if they have or have not used the sequences similar to humans because they haven’t told me. They would be bloody stupid if they had used those sequences!  As an aside, it is also odd that, even though Prof. Heinemann is correct in his statement that the plant and human genes are similar, he uses a sequence from another plant, not wheat, in his analysis.

But the way this issue has been raised seems unhelpful. By producing a press release as the decisions on this crop are made, rather than engaging with the decision-making process, two things have been lost. One is credibility. By not engaging with the decision-making process, but then releasing a scientifically backed query about the plants, you make it look like your aim is to disrupt, rather than inform. The second thing lost is the opportunity to improve the plants being produced. No company wants to sell a new strain of plants that would cause a human disease, or even target a human gene unexpectedly. If CSIRO haven’t thought about, and mitigated against, the issues raised, then they may have done if they had been informed earlier. Now there is mistrust and anger, neither of which helps the general public get the high quality, safe products they deserve.

So two problems here; secrecy because of intellectual property, and lobbying, not engagement. We need light not heat!

Actually it’s freezing here in Otago, so heat would be good too….

Isn’t the really interesting thing here the idea that plants might make double stranded RNA to specifically target genes in herbivores. When you eat a carrot, is it directly suppressing some of your genes? And if so what, and why? Isn’t Science cool?

0 Responses to “Does eating transgenic wheat destroy your liver?”

  • Great post, Peter, & very timely. Thank you. My first-year students were discussing exactly this sort of thing in lecture yesterday, & I’ve linked to this post on our moodle page 🙂

  • Great effort, Peter.

    In the presentation there is – “Therefore, this analysis provides an estimation of the plausibility that the GM wheat event could cause an adverse effect via the expression of these novel dsRNA molecules”.

    The report then goes on to some sequence analysis as you note.

    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 (i.e. including the non-coding regions of the transcript), it can’t be called either way without knowing the dsRNA sequence – ?

    • Thanks Grant.
      The report suggests two issues- a direct one of the plant gene sequences being similar enough to cause an effect in humans, which clearly can only be assessed if you know the sequence of the dsRNA constructs.
      The second is this idea that construct that make dsRNA will also produce novel dsRNA molecules, thus producing a random dsRNA effect that might also cause problems in humans. This seems a bit woolly.

      Part of the problem is lack of trust. Any decent scientist would make sure the dsRNA was in a non-conserved region, and test for novel RNAs. It would be nice to know, however, that that has been done. Do we have to take it on trust?

  • I agree with what you’re saying – my point really was just that I don’t see much value in the report showing those sequence analyses if you don’t know the sequence of the dsRNA. (Finding ‘identical’ genes aside.)

    Loose Q: there’s no patent that discloses the dsRNA sequence?

    PS – somewhere in editing that sentence a bit got cut, it ought to be “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 (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 – ?” *Sigh*

  • Without meaning to put a cat amongst the pigeons, I encountered this opinion piece in EMBO Reports that might interest readers of this thread whilst locating other papers:

    Stop worrying; start growing
    Risk research on GM crops is a dead parrot: it is time to start reaping the benefits of GM

    (Fans of Monty Python will get the dead parrot reference, which features in the text of the article.)

  • yep- without the dsRNA sequences this is all a shot in the dark.

    Nice to see a controversy caused by a single blast search with the wrong sequence!

    Nice EMBO piece too. If you Read Heinemann’s report it really states that there is a vague possible risk, but even that is unacceptable. As if non-GM food was always risk free.

  • The other issue I have with the press release is it is based on an analysis that has not been assessed by peer review. Every scientist makes mistakes and they owe it to themselves and their colleagues to have their work assessed by peer review before going public. Just in case there are flaws in the analysis that were not noticed.

    Without peer review this feels a lot like scaremongering and not very much like a genuine scientific concern about risk.

  • I’m pleased to see this attempt by the New Zealand science community to consider the issues we raised in our risk assessment of GM wheat. However, before too many fun rumours get the credibility of some kind of truth, I thought I’d briefly respond.

    “Nice to see a controversy caused by a single blast search with the wrong sequence!”

    Genetics Otago might want to get his facts straight. From the Office of the Gene Technology Regulator’s document: “The SEI and SEII genes were isolated from the wheat Aegilops tauschii (donor of the D genome in wheat) and Triticum aestivum, respectively.” For the risk assessment we did, we took the SEI sequence from CSIRO’s posting.

    And we did two blast searches thank you. 😉 (smile)

    “Part of the problem is lack of trust. Any decent scientist would make sure the dsRNA was in a non-conserved region, and test for novel RNAs. It would be nice to know, however, that that has been done. Do we have to take it on trust?”

    This in my view is common ground and thanks, Peter, for saying this. One can have trust in a good system to not be infallible.

    We have been in contact with FSANZ on this topic since 2004. While that is a different regulator, but they work closely with OGTR because their decisions are harmonised. This isn’t the first time the issues were raised in OGTR either. In fact, OGTR published a response to other submitters on the same topic in DIR 108. They responded:

    “Zhang et al 2011 was published subsequent to preparation of the consultation RARMP. It demonstrates that exogenous plant microRNA (miRNA) can regulate the expression of target genes in mammals. GM InVigor® x Roundup Ready® canola is not modified to express novel miRNAs.” Thus, they are aware of the exposure pathway, they are aware of the plausibility of an effect and they imply that in the case above it can be ignored because there was no intention to make a dsRNA in the canola. Note that they do not explicitly dismiss the relevance of the risk for plants intended to produce gene regulatory dsRNAs such as the wheat.

    If the work we describe has been done, then the results can be presented as an analysis that does not depend on releasing the sequences that were used. I agree with Peter that our analysis was an obvious thing to have done. So why the secrecy if it had been? Show us the track record of the analysis. Respond to requests for the analysis.

    But OGTR implies that this analysis was not considered in any formal risk assessment. They say: “The potential for allergic reactions in people, or toxicity in people and other organisms as a result of exposure to GM plants with altered grain starch composition as a result of the introduced RNAi constructs is not an identified risk and will not be assessed further.” To do a risk assessment, you have to identify a risk so that it can be considered. If it wasn’t an identified risk, then why would they consider it, much less ask for risk-specific data?

    While these posts on Sciblogs are illuminating for all sorts of reasons, what we need is a simple answer to this question: what was actually done to address the risk and where is the analysis?

  • Please see our media release on this issue.

    I am currently in communication with CSIRO, waiting for the exact post-transformation sequence/s of the GM wheat/s to be tested on humans, and planted in our environment, assuming they have actually been evaluated. I want these sequences independently tested. In Australia we don’t seem to have any molecular biologists who are paid to give regard to unknown unknowns.

  • Good to hear from you Jack! And thanks for pointing out what you have done, and why you used the sequence you did. Always happy to be corrected.

    Do you know if the regulators get to see the sequences used? Why can’t the actual constructs be released in a patent, making it clear that they are owned by somebody, but disclosing the sequence.

    I am being far too naive?

  • Hi Madeleine,

    good luck with getting the actual sequences, it is important to know what they are.

    What do you mean by independently tested? What sort of tests do you have in mind?

  • You raise excellent questions, Peter. I am sure that the regulator can request the sequences because they have the ability to keep them secret by agreement. A developer who refused a legitimate request from a regulator would risk getting their application denied. Whether or not OGTR asked for the sequences I don’t know.
    My guess is that the sequences do not need to be patented because CSIRO has a fundamental process patent. Again, this would have to be confirmed with them, but it is possible that only those licensing the technique from CSIRO would need to use a patent on sequences to protect their products. CSIRO products may be covered just by the process so it does not matter what sequences they use and as such would not need (for IP reasons) to disclose them.

  • Perhaps what is needed here is peer review! It is the, albeit flawed, gold standard for publication, why not for this kind of analysis?

  • I imagine in principle they could ask to demonstrate the safety without disclosing the dsRNA sequence using the whole plant, etc. – ? After all, the sequence analysis will only raise hypothetical concerns at best (as I recall the report noted), ditto for testing the dsRNA in isolation. I’d like to think these things come down to testing the final produce in the end. (Incidentally, as I wrote on here on sciblogs nearly three years ago. I’ve been here longer than I think sometimes!)

  • Hi Genetics Otago,

    re ‘independently tested’

    Before release into the environment, and before approval for human testing, I would’ve hoped that ‘someone’ at CSIRO or our OGTR had already evaluated the in-plant construct/s, various expected transcripts from it, searched for unexpected transcripts, including all associated dsRNAi.

    But I don’t remember reading in the OGTR doc (a year ago) that this had been done. In a new quick scan as a result of Jack Heinemann’s publication I have read that the OGTR noted that CSIRO hadn’t searched for plasmid residues. It seemed to have been approved for environmental release and human trial at a very early stage.

    I’d hope that CSIRO had run the in-plant sequence through something like BLAST as Jack Heinemann reported but if so it’s something that’s been done internally. I’m not prepared to sit back and trust it.

    I’ve read through a lot of the GM dossiers sent by Monsanto et al to FSANZ, also accessed and cited by the OGTR in the case of GM canola, and have been appalled to see what our regulators have ignored. I have met with people at FSANZ and have talked in person with one from the OGTR.

    I have an affectionate value for CSIRO and the work it does, but they do have commerical alliances with the worst of companies. With respect to GM they’ve been engaging in unsupportable rhetoric – we put out this release on what we considered to be disinformation about this wheat

    In its legislation FSANZ is obligated to serve the interests of trade and are compromised. Both the OGTR and FSANZ are compromised in serving Government agenda which is not representing the people in a number of areas related to GM. I don’t see any of these bodies as sufficiently independent from major coporate interests which includes the US state (check wikileaks cables ).

    Maybe if we get the sequence I will see if Jack Heinemann is willing to do it. Or maybe I’d find a friend who has used BLAST for these sort of matchings.

  • 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. Moreover, the vast majority of scientific documents that regulators are supplied by developers have never been through a blind peer-review process and published before they are given to a regulator. And very little more ever is published. But for some reason the scientific community is being very quiet on that even though the results of those processes impact our daily lives.
    INBI underwent a peer-review process that was open – you know who read the report before a final version was released. In contrast, can you tell me who certifies the OGTR risk assessment or CSIRO documents upon which the risk assessment is based?
    In addition, INBI has released all the results and methodology and assumptions for review by folks like you, and you have made a review and from that you know that peer-reviewers are also not infallible. Perhaps the questions you and others here are asking should also be directed to the industry (both private and public) and the regulators and why you seem comfortable with their similar procedures, rather than implying that the standard of our science was suspect because we didn’t use a journal.

    • Sorry, my comment was really that the risk assessments would be best with blind peer review and final publication. On the other hand, I think it important and necessary that opinions from scientists can be put into the public, as long as it is clear they are opinions. Scientists should be public figures, in my opinion, but also should accept that a statement they make without peer review carries less weight than one that is.

  • The problem I have as an Australian citizen is that there is no “Science Ombudsman” to take my complaints about decisions by FSANZ or the OGTR. The Auditor General has looked at FSANZ and made comments and recommendations about their behaviour with regard to their legislation/regulation and standards, but they stopped their review where the science began. Because there are so few literate people in this field (and I think it was designed that way) it’s very difficult for me as an ordinary citizen to get some scientific redress.

  • Madeleine,

    If I have time I’d run a few searches, etc., myself (I’m a computational biologist, an independent consultant)* but I’d think that in the end sequence analysis would still really only raise hypothetical concerns. E.g. You’d still have to show it made it to the liver or wherever in amounts that would cause a biological effect, etc. – experimental studies. Simple sequence searches might give a direction to check, if warranted, but they wouldn’t be conclusive, an end point.

    * And for myself!

  • This is undoubtedly a case of yelling “fire” in a crowded theater. It is science-by-press-release, refuge of cranks. And I am stunned that anyone who considers themselves a responsible scientist would be part of creating this kind of misinformation that has misled people who don’t understand what’s going on:

    That’s incredibly irresponsible fear-mongering.

    That said, I have also looked at the sequence analysis. The first appendix uses a 25,000 nt piece (which may or may not be the right sequence) in the same way a fishing trawler uses a drag net. There’s no basis for any conclusions from that.

    Appendix 2 uses a second and different length piece which is not described (only 5000+ bases). So it’s impossible to know even if we had the putative CSIRO match if this has any basis in reality.

    It’s a terrible analysis and a terrible misinformation campaign. Shameful, really.

  • It’s just come to my attention that Jack (Dr. Heinemann) has written as one of two ‘sides’ of a “he said, she said” style ‘debate’ post for the NZ Herald newspaper.* Readers here may wish to contribute their thoughts there, too.

    (I’ve posted a pointer to this article, but in past experience the newspaper sites seem reluctant to accept links to other sites, so I’m not especially confident that they’ll publish it.)

    * I’m personally not a fan of this approach as it generally only creates more heat than insight, never mind genuine discussion. (I’ve written about some of the general issues of media presentations of these kinds a few years ago on my blog.) One issue, for example, is that some readers are perceiving it as business v. science. Jack’s views represent his opinion, not the scientific community as a whole (as can be seen from Peter’s response and the discussion here). I’ll try add a comment to that effect over there.

  • It’s so funny to me that some scientists suddenly become wizards of economics on this topic. And if their economics is as…er…lacking as their biological analysis….well…

    I won’t vote over there, this is your decision to make. But here’s what I would vote: No, you should not grow GM crops. It is imperative that you permit the US to kick your butts. This is because we’ll be needing to have butts to kick after China kicks ours. And they are going full-bore on plant technologies, despite the fictions you hear from Greenpeace.

  • Mary,

    One of the problems with the NZ Herald’s page is that to comment you are forced to vote, even if you just wanted to make a comment. It’s frustrating for me as I had no wish to say yea or nay.

    The voting thing is silly anyway. As everyone must, or should, know internet polls aren’t very meaningful. (I’m being polite.) In fact one science writer with a large following encourages his readers to “bomb” polls not just to skew them, but also to make the point of how meaningless they were!

  • What’s shameful (a propos of “Mary”‘s comments) is the way in which any scientist whose research raises concerns or even asks inconvenient questions about any aspect of GM is subjected to a barrage of ad hominem attacks, none of which address the concerns or questions that have been raised.

    I hope Sciblogs will discourage such attacks.

  • Joanna: By-passing the legitimate process of scientific review and comment to take a baseless, speculative case based on a terrible analysis to misinform the public directly is a foul strategy. It is a fear-based method that should repulse anyone who values the public discourse–on this topic or any other.

    If you have any actual evidence that this purported case is valid, deliver it. Because I’ve looked at the claim and it’s not.

  • “Mary”:

    “I’ve looked at the claim and it’s not” is not actually an adequate rebuttal of a detailed scientific study.

    By “by-passing the legitimate process of scientific review”, I assume you mean that it was not published in a peer-reviewed journal. Risk assessments and the reports commissioned by risk-assessment agencies are also not published in peer-reviewed scientific journals. Do they in your view by-pass the legitimate process of scientific review?

    “Baseless” is an empty allegation if you do not point by point refute the actual case made in the reports.

    “Speculative”: all risk assessment is speculative, if by that you mean consideration of what may occur rather than description of what has already occurred.

    “Terrible analysis”: see point re “baseless”.

    “To misinform the public”/”foul strategy”/ “fear-based method”: now you are imputing motive and once again resorting to ad hominem attack.

    It is not for me to supply “evidence that this purported case is valid”; the reports themselves supply the evidence. It is for you to refute the evidence supplied in the reports rather than making sweeping, unsubstantiated rejections and ad hominem attacks.

  • Exactly, “Joanna”–this was not published in a peer-reviewed manner, nor was it part of the public process in which these assessments are handled.

    It is absolutely possible to hire some scientists and produce “reports” that meet one’s agenda. And those absolutely should carry much less weight. The IPCC had to stop using gray literature of that sort because of the bias and errors. I’m with the IPCC on that.

    Here is my assessment of the results, which I had already described in a comment, and is no different in longer form: the choice of sequence is not legitimate, and the results cannot be replicated with the information that was provided. It is, without question, a terrible analysis. And the massively inflated claims are unfounded based on the sequence selected and the work that was provided.

    I can see why this strategy had to be used. It would never have made the grade of peer review.

    The analysis is bad enough, but I think the far bigger problem is the damage to the public understanding, which was willful in this case. They sought this strategy out.

    The amount of misunderstanding and anxiety they have spawned is appalling. It is despicable to take advantage of credulous people’s fears in this way. They *own* this huge volume of misinformation which will persist for years in the popular mythology.

    It is conduct unbecoming scientists, and it should be rebuked. I don’t really care if you don’t like the descriptions of it–sadly, it’s accurate to call this behavior shameful, irresponsible, foul, and fear-based. It has negative consequence for the public discourse–and I have the evidence to show that as well. People are now more misinformed and fearful than they were before.

    That said, it did make me laugh to see that David Icke thought these theories were worth propagating. If that’s the type of person this theory attracts: Mike Adams, Alex Jones, etc–and it did seem to attract mostly that sort, that really speaks for itself. Responsible scientists would be horrified to be aligned with that list. They’ll have enough problems to deal with if conspiracy nuts, fiction writers, and conflama artists are the fans and major supporters of this information, best of luck. They don’t make good allies in the long term, though, because truth and evidence are not among the things they value.

    They sciencyness may be able to fool some people in the short term, but truth wins. Science will prevail. Eventually.

  • “Mary” (unlike you, I am not posting under the cover of anonymity):

    First, have you sent your preliminary analysis to the authors and asked for a response? Isn’t that how science is supposed to work?

    Second, you continue to raise objections that were answered above by Jack Heinemann, without any reference to Heinemann’s responses. Is that how science works? I suggest you read the discussion above between Peter and Jack before continuing to make these charges.

    Third, in addition to ad hominem attacks (which you continue) you are now using guilt by association. If we were all tarred by the qualities and actions of anyone who ever agreed with us, we would never say anything. Many scientists have been in the position of having their work used in questionable ways.

    An appropriate response to the reports would be to address the concerns raised: e.g., show that the actual sequences used have no matches in the human genome.

  • Ha ha ha…”how science is supposed to work”. Charming “Joanna”. See #FAIL1 of the SafeFood hired guns PR strategy. They dropped this in the public domain–they own the consequences. If they wanted crowd-sourced peer review, they can have it. And they won’t like it.

    These objections are not answered. The unsuitable giant sequence choice is not acceptable, and therefore all the subsequent claims are bollocks anyway. If you have started with garbage, your output is garbage. And then: why did Jack publish the Appendix A with mismatched parameters? Why didn’t Jack provide the necessary details of the second one? But none of those things really matter if the initial huge sequence was unsuitable as a starting point anyway.

    But I don’t think you really care about the science details. Or you wouldn’t be defending a sub-par analysis in the first place. I think you have other issues.

    It’s clear to me why the ratcheting up of the fear-factor is the new strategy. What we are seeing are the plants that have health and nutrition benefits coming along. Many of these are coming from academic, government, and non-profit projects. So the old Monsanto bogey-man won’t play. And consumers are going to start to want to give these improved plants a try.

    The new strategy is to make people afraid–very very afraid. It’s rational as a method to use. It’s abhorrent–but would make sense to those philosophically opposed to biotechnology who are out of actual evidence and bogey-men.

    Hitch your wagon to the fear strategy if you want. But polluting the science-communication environment is a reprehensible tactic.

    Dan Kahan has studied this. What he suggests has happened in climate discussions is the pollution of the public discourse. Watching that happen in real-time on this topic is truly maddening. Those responsible for it should be held accountable and chastised by the science community for misuse of the public trust. I realize there will be no actual consequences to spreading misinformation in this charade, and SafeFood and their science team already got what they wanted. And in our craven media’s fear-based news cycles, I’m sure someone will turn to them in the future for further fear and obfuscation.

    But in a just world they would be shunned.

  • I see. If I don’t agree with you, then I don’t really care about the science details and I “have other issues”. Back to ad hominem.

  • I think I take the alternative view. I have said that there are some issues here with the wheat proposed, issues that probably go away if you examine the sequences used to block the wheat genes. However it does seem irresponsible to explicitly link the possibility of an RNAi effect and a human disease.

    We don’t know if the sequences are similar to the human gene, we don’t know if they will transfer their effect to the human, we don’t know if they would have a significant suppressive effect on the human gene, we don’t know how much of a suppression, in which tissues, would lead to disease.

    On this basis, its seems a bit shouty to say that eating this wheat will cause this disease.

    However, lets take the situation that has been published. Prof Heinemann’s report quotes the paper from Zhang et al (, that shows that rice produces a miRNA that targets the mouse/and human LDLRAP1 gene. Their data shows that this leads, in some situations (some of which aren’t physiological), to a more than 50% reduction in LDLRAP1 protein. LDLRAP1 is linked to a human disease Familial Hypercholestrolemia ( The disease is recessive, meaning that you need more than 50% reduction in expression to get a phenotype. Surely here we have much better data linking the consumption of a plant product with a human disease, yet I don’t see the same scientists campaigning against rice eating.
    The fact is that eating rice is perfectly safe, genetics is more complex than just reducing expression of a gene leading to disease. In what cells this happens, how much it happens, when it happens, how long term etc it is are all vital questions to ask.

    It is disappointing to see that the reports presented, which contain complex genetics, can be, easily, distilled into the, frankly horrifying, tweet, pointed out by Mary above. Surely no one can say that that response is a good outcome?

  • As far as I know, none of the scientists whose work is being discussed said anything like “eating this wheat will cause this disease”.

    As far as I know, none is campaigning against wheat-eating (which your statement about rice-eating seems to imply). The logic of the rice example, or at least its relevance here, escapes me.

    The last paragraph is again using guilt by association. If we all had to live by the principle “Don’t do or say anything that could be distorted by others”, we would do and say nothing of consequence. How can you hold the authors of the reports (“which contain complex genetics”) responsible for some random person’s distortion, in a tweet of all things (tweets not being known for their subtlety or profundity)? I don’t understand why you are inventing new rules for these scientists. To play with your rice example for a moment, if you are so concerned about research that gets distorted by others, why are you not outraged at the kind of systemic problem of distortion by the researchers themselves, as reported here?

  • Hi Joanna,

    you are quite right, nobody in the reports states the wheat will cause this disease, but they come quite close (eg from Prof Carman)

    “Consequently, it is clear that there is an obvious risk to animals and people who eat these GM wheat varieties. That is, there is evidence that dsRNA from GM plants may survive digestion to enter the tissues of the body, where it may silence a gene in the host. Furthermore, there is evidence of a specific gene that may be silenced in the host – a similar gene to the one that is silenced on purpose in the GM wheat variety. There is also evidence that if this gene was silenced in animals and people, it could cause serious ill-health and even death.”

    More to the point, major press has taken it that way, and not been corrected. I think we all are responsible if our statements, and indeed should try and correct them if we give the wrong impression. Is that what has happened here? Do you think the reports and their intent have been misrepresented?

    I clearly didn’t get my point with the rice example across. I just think there is better evidence (though still incredibly speculative) for a problem with this example, than we have with the GM wheat, but still no public statements have occurred.

    Finally, I have spoken publicly against that fact that so much basic research is spun as medically relevant rather than an investigation in biology. I have spoken even more strongly when the medical spin has resulted in poor experiments.

  • Re your last point: I’m very glad to hear it!

    On the question of rice and risk: Isn’t this where context matters, namely the fact that humans have been eating rice for many many generations, and so we can be pretty confident that rice as it has existed for generations is not toxic for most people — as opposed to an introduced construct without such a history? (Which is not to say that this argument–that a food must be OK because it has been around a long time–doesn’t have its limits, as can be seen with gluten-intolerance, lactose-intolerance, nut allergies, etc.)

    On the media: If they are saying the things that have been claimed, then, yes, I think the authors are being misrepresented. And, yes, if I were misrepresented by the media I would attempt to get it corrected–and maybe the authors have attempted to do so. But unless they were actually misquoted (and maybe not even then), they wouldn’t necessarily have any success. But that’s major media. I don’t think it is reasonable to expect people to track down every tweet or blog that might have miscontrued their work! And again, I don’t see this rule being applied to others. So when major media report that “the gene for [Alzhiemers, autism, ADHD,…xenophobia]” has been discovered, I see no evidence that researchers rush to demand that such distortions be corrected.

  • Interesting to see Madeleine Love from anti-GM campaigners group MADGE Australia (Mothers are Demystifying Genetic Engineering) is here taking pot shots from the sidelines at someone pointing out that this “study” was a deliberate attempt to scare the public about genetic engineering in general. It is interesting because in the hours after the media release of this science by media her anti-GM organisation’s twitter account tweeted the story at least four separate times using language intended to spread fear. (see below for the tweets). That was just from MADGE the organisation and does not include their personal tweets. . This is exactly what the safe food foundation desired and is exactly what Roush warned about in his response to the “study”.

    “Have you seen the big news on the GM wheat that could cause liver failure and genetic disease?”…

    “Prof Heinemann explains how #GMO wheat could turn off human genes. Prof Rick Roush says its all fine. What do u think?”…

    ” Apart from the possibility of causing liver failure and genetic illness #GMO wheat looks great!… ”

    “Opposition calls for rethink on #GMO wheat trial – potentially fatal to humans… @abcnews ”

    So much for demystifying and everything going to plan for the safe food foundation. This is not science!

  • Chris Kelly is a MADGE troll. Beyond that I don’t know who he is though I have asked many times. I’m reading a text on rhetoric and fallacies, parsing a GM proponent’s work as I go – I admired Joanna’s calm referenced dissection. As a person with a science background this language of politicians, advertisers and barristers is new to me. I didn’t read very much of ‘Mary’s’ posts because they were rhetorically inflamed – if he has science-relevant points to make he should make them using the language of science.
    “Taking pot shots from the sidelines” is ad hominem word use, in an attempt to slur.
    “anti-GM” in this context is also an ad hominem slur and it is incorrect. MADGE is not against contained, public-interest, patent-free Genetic Engineering.
    In this particular case the risk has not been quantified, there being so little preliminary work reported. In his review of the Heinemann and Carman work, Dr Michael Antonio, reader in molecular genetics at Kings College in the UK, has however, on the basis of so many matches, concluded that it is not a matter of whether there will be gene function disturbances, but the degree to which there will be such effects.

  • Let’s look at the SafeFood Media Release page :
    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’s paragraph 1. Now why do we think people are coming to the wrong conclusion again? Who is responsible for that?

    This presumption also relies heavily on the Zhang paper concept being reproducible. That is not clear at this time. In fact, I’m with Phil on this one:
    But RNAi expert Phillip Zamore, investigator at the Howard Hughes Medical Institute and Gretchen Stone Cook Professor of Biomedical Sciences at the University of Massachusetts Medical School, thinks that rushing to any conclusions about GM relevance is premature. “If you could dream up a molecule that you would worry about [for GM foods], this wouldn’t be it,” he said.

    But the whole foundation still resides on the terrible BLAST analysis. If that sequence is poorly chosen and misused–and it seems to be–then all the downstream hair-flambé is unfounded on top of that, whether it was just a little flamy or conflagration.

  • “When you eat a carrot, is it directly suppressing some of your genes? And if so what, and why?”

    I don’t know about carrots, but I’ve learned a little about soy and particularly about genistein (an isoflavone found in a number of plants including soybeans).

    In my early 40’s I began having fragility fractures from osteoporosis. I suffered continued bone loss on oral bisphosphonates and my treatment was changed to teriparatide (Forteo). After 2 years on Forteo (the maximum), I received an IV bisphosphonate and again had bone loss (not to mention osteonecrosis of the jaw).

    It appeared that my next treatment option would be denosumab (Prolia), a fully human monoclonal antibody that inhibits the maturation of osteoclasts by binding to and inhibiting RANKL.

    Instead of Prolia, I decided to try genistein in the form of the “medical food” marketed as Fosteum. My rationale was that genistein is known to suppress RANKL signaling-related gene expression in osteoclastic cells.

    Greatly oversimplified, it appeared that Prolia and genistein have different mechanisms of action, but both with the net effect of slowing bone resorption by inhibiting the maturation of osteoclasts via RANK/RANKL.

    After 2 years of Fosteum (one cap twice daily), my DEXA scan showed “stable” T scores–no improvement in bone density, but an apparent “arrest” of the dynamic bone loss seen on previous scans.

    I’m still taking Fosteum, but it would be easily possible to ingest a comparable amount of genistein through diet. I have autoimmune disease and had already discovered, fortuitously, on my own, that I felt better after introducing fermented soy into my diet. I backed off dietary soy when I began taking Fosteum, but for me two things are clear.

    “Medical food” is not a new concept. (Didn’t Hippocrates have something to say about food being medicine and medicine being food?)

    It’s well established that food can and does activate/silence human genes. Our understanding of the impact of food on gene expression is mostly in terms of macronutrients (e.g., amino acids) and micronutrients (e.g., vitamins, minerals), but I personally am fascinated with an evolutionary perspective that predicts significant conservation of gene order between organisms (plant and animal). As more complete genomes are sequenced, and the resultant sequences are compared/contrasted, I think we’re going to find that we (humans) are more closely related to our food than we ever dreamed possible. Scopes monkey trial? Just you wait–someday we’ll be fighting against textbooks that talk about the evolution of man from plants (or maybe, more realistically, from the organism that was/is the shared common ancestor of all life on earth, plant and animal).

    I think if we knew more about the influence of plant genes on human gene expression, we’d find that much of what we’re trying to create in the lab is already present in nature. I’m not naive enough to think that “big money” will ever be invested in efforts to show how nature has already given us “an herb for every disease,” but I can hope? In the meantime, I’ll continue to eat from my own garden and do whatever else I can to avoid bioengineered (GM) food.

  • Sounds really risky and like something catastrophic or unexpected could happen. It could even happen years down the road if there are genetic changes brought on by dozens of possible influences. Let them play in their labs, but don;t let this stuff out by any means. If you want less starch, eat more meat! how simple could that be, no lab, no risk, no genetic tweaking, eat the right stuff! sounds pretty simple to me. Why are they even dreaming up products which really have no redeeming function. how about wheat that is less sensitive to moisture or drought? How about stronger or better/bigger kernals…that would really help!

  • Lactose intolerant individuals have insufficient levels of lactase, an enzyme that catalyzes hydrolysis of lactose into glucose and galactose, in their digestive system. In most cases this causes symptoms which may include abdominal bloating and cramps, flatulence, diarrhea, nausea, borborygmi (rumbling stomach), or vomiting after consuming significant amounts of lactose.“’^

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  • Millions of research dollars had been expended to produce a …”new wheat variety” which simple “AIMS to increase the amount of resistant starch, making this starch less easy to digest with apparent health benefits for the consumer. To make this variety, CSIRO has used a transgene that suppresses two plant genes, genes that make easy-to-digest starch.”

    In adition, millions of dollars will be expended to revert the damages if the risks come true – let’s not forget, for instance, the terrible case of DDT.

    All this while the alternative way to reduce the amount of rapidly digested starch in an person is to change its diet.

    If I were Goverment, I would invest all resources in education. Let’s take for example the “five-a-day” serves campaing. It rises questions and movilises the adult – holding the moratorium – and it will produce the wanted change in the children’s generation. Certenly will erradicate excesive rapidly-digested-starch consumption in our diets.

    Finally, sometimes appear to me that the solutions, invised by few chief scientists that then derive in multimillion-dollar research projects, are folowed up without much investment than a few pages return-over-investment analysis. Would’nt have been a ridiculus project to have silenced few genes in the tobaco plant to prevent all deseases now well known, in particular from today’s view that there is no better solution than quiting smoking all together?

    Many thanks to the ones that hold the discussion on a high level, such as Prof. Jack Heinemann does.

  • Horrible news regarding children’s livers function.
    The generational constant ‘stress response’ ( sugar metabolism),processed food diets, environmental toxins ,transgenic (effects on DNA gene pattern from kidneys) seems to have altered children livers and how they metabolize sugar and filter their blood.
    (Altered Liver function = increases in obesity and diabetes )

    Once schools were not tense,fearful, nervous places- today they are. Imagine how always having the stress response “on” effects children.We did not grow up with the atmosphere of fear and stress that they do today.
    But on a postive note