Updated – Experts on regulatory bodies’ approach to GM products

UPDATED: Independent experts have responded to accusations that lax regulations are allowing potentially unsafe genetically modified products into  New Zealand and Australia.

Safe soy? A group of academics claim GM products such as soy beans are not being subjected to sufficient scrutiny from regulators.
Safe soy? A group of academics claim GM products such as soy beans are not being subjected to sufficient scrutiny from regulators.

A recent analysis by Professor Jack Heinemann, director of the University of Canterbury’s Centre for Integrated Research in Biosafety, and colleagues, critically examined several regulatory bodies and how they assess genetically modified organisms carrying a modification that produces a molecule that can inhibit other genes (double stranded RNA; dsRNA).

The study, published on Friday in the journal Environment International, concluded that, “regulatory bodies are not adequately assessing the risks of dsRNA-producing GM products”, and suggests a formal assessment procedure for dsRNA-based products.

The authors claim that New Zealanders are being put at risk by Food Standards Australia New Zealand because the standards body is approving foods such as soybeans, margarines and chocolate that may contain a GM molecule that has yet to be proved safe for consumption.

See study paper and press release, and a media report that ran in The Press.

Update: a follow up article in the The Press further explores the issue.

Update: Food Standards Australia New Zealand has considered paper and issued a response, full expert commentary is now available here.

Additional comment posted  22/5/13

Click here to read new comment from Prof Ian Shaw, University of Canterbury.

Additional comment posted 8/4/13:

Associate Professor Peter Dearden, Director of Genetics Otago, Biochemistry Department, University of Otago, comments:

“Prof Heinemann’s paper in Environment International is a good review of some of the problems associated with using double stranded RNA (dsRNA) as a biotechnological tool in GM plants and animals.

“Double stranded RNA has been shown to be stable, can be transported into cells and does regulate genes. There is evidence, some of which is disputed, that small RNA molecules can cross into other species in food, and may regulate genes.

“Part of the problem, as is pointed out by Prof Heinemann, is that this mechanism of gene regulation was not understood well until recently, and assumptions about the behaviour of normal RNA molecules do not apply to double stranded ones.

“The good news is that small RNAs are easy to detect with modern sequencing techniques, and it is relatively easy to make sure such RNAs do not have targets that might be affected in humans. I think it important that this is done and reported on in risk assessments of GM food and agree with Prof Heinemann on this point. That this hasn’t routinely been done in the past is probably due to this being more a new area of understanding than anything else.

“The bad news is that, of course, the combining of genomes through natural breeding may also produce unintended RNAs to be formed. That this has not been a problem implies that this is a very small risk or possibility.

“My own opinion is that dsRNA as a way to manipulate plant traits is a very useful tool. Ensuring there are no off-target effects is relatively easy to achieve and should be something regulators investigate. Developing new plant/animal strains, either through traditional breeding or genetic modification, will be one of the tools that help us improve primary production. Any regulatory system must rigorously take into account risks and the precautionary principle, but we also must not throw out the baby with the bathwater.”

Previous comments:

Professor Peter Langridge,  chief executive of the Australian Centre for Plant Functional Genomics, University of Adelaide comments:

“It is disappointing that these authors continue to ignore the bulk of the scientific literature, but in this case they are even ignoring common sense.  The suggestion that regulatory agencies do not consider dsRNA in their assessments is ridiculous.  I have actually been involved in a workshop organised by the Australian and New Zealand regulators to discuss this and other technologies in great detail.

“The regulatory agencies are not only fully aware of the technology but they are actively seeking scientific input into the safety assessment. We are fortunate in Australia and New Zealand to have very effective and profession regulatory procedures that have ensured we now enjoy the safest food in our history.

“It is typical of the scare tactics used by these ideological opponents of GM technology, to totally ignore the fact that dsRNA is present in most food we consume and is therefore intrinsically harmless. In their article, this group proposes regulatory procedures that are clearly designed to block the technology not address safety issues. The data and information they would require has all been generated for GM foods but these authors choose to ignore this information.  In my opinion the approach adopted by this group is based on misinformation and distortion of the facts.  They do not appear to have any interest in informed scientific debate.

“In Australia, Dr Carman used her lawyers to try and silence scientific criticism of one of her recent press releases. If anyone would like to get accurate information on the safety of these new technologies they should look at some of the detailed studies and discussion papers available from the website of the European Food Safety Authority.”

Dr David Tribe, Senior Lecturer in Food Biotechnology and Microbiology, Agriculture and Food Systems at University of Melbourne, comments:

“My main response is quite simple: the ds RNAs that are discussed in [the paper] are in every bit of food we eat, and in perhaps every plant and animal on the planet, and have been for millennia.

“Why GM food is singled out for special risk attention by this paper is rather puzzling. All plants pose the same questions, perhaps more so than GM crops because they are not scrutinised to the same extent as GM crops by safety authorities like FSANZ. Any GM crop can be scrutinised using modern bioinformatics methods to ensure any issues about ds RNA or RNA silencing are addressed and avoided in the early stages of crop development.”

Prof Ian Shaw, Professor of Toxicology, University of Canterbury, comments (response received prior to release of FSANZ report):

“This is a very complex and emerging field – there are no firm facts, but a great deal of experimentation that is producing results that are sometimes not in absolute agreement, but most seem to be pointing in the same direction.  This ‘direction’ is being accepted amongst experts in the field as an indicator of what is actually happening.

“In brief; a relatively recently discovered form of RNA, double stranded (ds) RNA is accepted as a key player in gene regulation.  As a result of this it is likely that the GM industry will focus on dsRNA modifications as a means of controlling gene expression in the future.  This is a clever idea, but has significant associated safety issues because little is known about what happens to dsRNA in the environment and consumers.  dsRNA is involved in gene silencing – the process by which a gene is ‘permanently’ switched off – and since silenced genes can be inherited there are multigenerational implications of the effects of dsRNA. This is the new, and very exciting, science of epigenetics.  It flies in the face of Darwinism because environmental experiences (e.g. exposures) can alter genes in a way that the ‘experience’ can be inherited without conventional changes to DNA bases which make up genes – this is the Nurture vs Nature debate that Darwin and Lamarck had in the late 1800s.  Darwin won that round, but the debate has been reopened with our increasing understanding of epigenetics and Nurture is not being dismissed as lightly this time around!

“In summary, genes can be affected by environment (e.g. exposures); therefore, if gene regulators like dsRNAs get out into our environment or are components of our food what will they do to our genes or the genes of other creatures in the environment?

“In order to answer this important question we need to understand how stable dsRNAs are.  If they are unstable they are unlikely to cause a significant problem because they would degrade in the environment or the digestive tracts of animals that consume them.  Research has shown that dsRNAs are remarkably stable – even to the strong acids of the digestive system.  They have been shown to survive insect digestion and found in their circulatory systems thus giving the potential for unintended gene regulation in the insect consumers.  Very much less is known about their stability and uptake in mammals.

“All of this evidence and the fact that unintended gene silencing is a common outcome of genetic modification (GM) means that we should consider the possible effects of dsRNAs in human consumers, and the environment more generally, before we allow genetically modified organisms (GMOs) out into the environment or to be used in food production.

“Since the dsRNA story is recent, the current processes used by regulatory authorities (e.g. FSANZ) to assess the safety of GMOs do not consider dsRNA as a hazard and thus do not include them in risk assessment.  Perhaps the only time a dsRNA would be subject to risk assessment by a regulatory authority would be if the dsRNA per se was the active principal (e.g. resulted in pesticidal activity) of a GM product.  ‘Conventional’ RNA (i.e. single stranded (ss) RNA) has been considered as part of risk assessments in the past because it has a gene product – i.e. a protein – that might have an effect on non-target species (e.g. humans); dsRNA slips through this net because it does not have a gene product, but rather causes its effects by changing the activity of other genes.

“There is very little hard evidence in the scientific literature on the effects of ‘alien’ dsRNAs on humans; however, there is significant data on the plant/insect interface.  Clearly more research is necessary before any robust decisions can be made about human exposure to alien dsRNA from GM food.  However, in my opinion, the evidence is mounting and work in insects proves the point that dsRNA can be absorbed from GM food plants by insects and subsequently affect the insect’s genes that we should apply the Precautionary Principal.  If we simply apply the dogma, ‘there’s no scientific evidence and therefore we can’t regulate’ (remembering, of course, that lack of evidence is not negative evidence!) we will facilitate the release of dsRNAs with unknown effects into our environment and food chain with the potential to alter genes that might be inherited thus potentially resulting in multigenerational effects.

“Heinemann et al point out that the regulatory process (e.g. that used by FSANZ) utilises input from regulators, external scientific experts, and information from the scientific literature to make regulatory decisions.  This is a good and robust process.  However, currently data relating to dsRNAs and their effects are not required as part of the dossier supplied to a regulatory authority (e.g. FSANZ) as part of the regulatory process for assessing GM foods.  Therefore, dsRNAs are not considered during the risk assessment.  I agree with Heinemannet al; THEY SHOULD BE