Potentially Dangerous Virus Gene Hidden in Commercial GM Crops
The European Food Safety Authority has just discovered a virus
gene in GM crops it has been approving over the past twenty years; a thorough
independent risk assessment based on existing data shows that the only
reasonable course of action is a total recall of all affected GM crops. Dr Jonathan Latham and Dr Allison
A belated discovery with serious ramifications for safety
European Food Safety Authority (EFSA) has belatedly discovered that the most
common genetic regulatory sequence in commercial GMOs
also encodes a significant fragment of a viral gene. The finding – published
quietly in a new journal  - has serious ramifications for crop biotechnology
and its regulation, but possibly even more so for consumers and farmers. There are
clear indications that this viral gene (called Gene VI) might not be safe for
human consumption, although the authors fall short of stating that. It also may
disturb the normal functioning of crops, including their natural pest
The authors, Nancy Podevin from the European Food
Safety Authority (EFSA) and Patrick du Jardin at University of Liege in
Belgium, discovered that of the 86 different transgenic events (unique insertions of
foreign DNA) commercialized to-date in the United States
54 contain portions of Gene VI within them. They all have the regulatory
sequence called the CaMV 35S promoter (from the cauliflower mosaic virus CaMV),
the most commonly used for driving gene expression
in GMOs. The
events therefore include some of the most widely grown GM crops all over the
world such as Roundup Ready soybeans (40-3-2) and MON810 maize. Also included
is the controversial NK603 maize recently reported to cause tumours in rats 
(see also  GM
Cancer Warning Can No Longer Be Ignored, SiS
The researchers themselves concluded that the presence of
segments of Gene VI “might result in unintended phenotypic changes.” They
reached this conclusion because similar fragments of Gene VI have already been
shown to be active on their own .
general, viral genes expressed in plants raise both agronomic and human health
concerns [5, 6]. That is
because many viral genes function to disable their host in order to facilitate
pathogen invasion, often by incapacitating
specific anti-pathogen defences. Incorporating such genes could clearly lead to
undesirable and unexpected outcomes in agriculture. Furthermore, viruses that
infect plants are often not that different from viruses that infect humans. For
example, sometimes the genes of human and plant viruses are interchangeable,
while on other occasions inserting plant viral fragments as transgenes has
caused the genetically altered plant to become susceptible to an animal virus .
Thus, in various ways, inserting viral genes accidentally into crop plants and
the food supply confers a significant potential for harm. (Editor’s comment:
there is also evidence that the CaMV 35S promoter may actually induce
transcription factors for HIV and other pathogenic viruses  New Evidence Links
CaMV 35S Promoter to HIV Transcription, ISIS scientific publication.)
The discovery of Gene VI in commercial GMO crops by a scientist within EFSA must have presented
regulators with sharply divergent options. They could
recall all CaMV Gene VI-containing crops (in Europe that would mean revoking
importation and planting approvals) or undertake a retrospective risk
assessment of the CaMV promoter and its Gene VI sequences and hope to give it a
clean bill of health. They clearly took the latter option as the easy way out. Recalling all GMOs would be a massive political and
financial decision and would also be a huge embarrassment to the regulators
themselves. But it would leave very few GMO crops on
the market and might even mean the end of crop biotechnology.
Regulators, if they had been doing their proper
job, would have had a third option to gauge the seriousness of any potential
GMO hazard. GMO monitoring - required by EU regulations - ought to have enabled
them to find out if deaths, illnesses, or crop failures have been reported by
farmers or health officials that could be correlated with the Gene VI sequence.
Unfortunately, not one country has carried
through on promises to officially and scientifically monitor any hazardous
consequences of GMOs. EFSA regulators might now be regretting their failure to
implement meaningful GMO monitoring. It would be a good question for European
politicians to ask EFSA and for the board of EFSA to ask the GMO panel - whose job it is to implement monitoring - why monitoring
was not carried out.
Searching the database for allergens, the main
thrust of Podevin and du Jardin’s paper , is just a distraction, perhaps to
reassure the public that Gene VI does not contain a known allergen,
while the more serious potential hazards are buried in the false reassurance.
Let us look in more detail at
Gene VI and its known properties, and their safety implications.
The many functions of Gene VI
Gene VI, like most plant viral genes, produces a protein that is
multifunctional. It has four known roles in the viral infection cycle. The
first is to participate in the assembly of virus particles. The second is to
suppress anti-pathogen defenses by inhibiting a general cellular system called
RNA silencing . Third, Gene VI has the highly unusual function of
transactivating (described below) the long RNA (the 35S RNA) produced by CaMV .
Fourth, unconnected to these other mechanisms, Gene VI has very recently been
shown to make plants highly susceptible to a bacterial pathogen ; it does
this by interfering with a common anti-pathogen defence mechanism in plants. We
shall concentrate on those functions of Gene VI that have important safety
Gene VI inhibits RNA silencing
RNA silencing is a mechanism for controlling gene expression at
the level of RNA abundance . It is also an important antiviral defence
in both plants and animals, and therefore most viruses have evolved genes (like
Gene VI) that disable it .
attribute of Gene VI raises two obvious biosafety concerns: it will lead to
aberrant gene expression in GMO crop plants, with unknown consequences, and it
will interfere with the ability of plants to defend themselves against viral
pathogens. There are numerous experiments showing that, in general, viral
proteins that disable gene silencing enhance infection by a wide spectrum of
Gene VI is a unique transactivator of gene expression
organisms make proteins by a mechanism in which only one protein is produced by
each passage of a ribosome along a messenger RNA (mRNA). Once that protein is
completed the ribosome dissociates from the mRNA. However, in a CaMV-infected
plant cell, or as a transgene, Gene VI directs the
ribosome to get back on an mRNA (reinitiate) and produce the next protein in
line on the mRNA, if there is one. This property of Gene VI enables CaMV to
produce multiple proteins from a single long RNA (the 35S RNA). Importantly,
this function of Gene VI (which is called transactivation) is not limited to
the 35S RNA. Gene VI seems able to transactivate cellular mRNA [14, 15]. There
are likely to be thousands of mRNA molecules having a short or long
protein coding sequence following the primary one. These secondary coding
sequences could be expressed in cells where Gene VI is expressed. The result
will presumably be production of numerous random proteins within cells. The
biosafety implications of this are difficult to assess. These proteins could be
allergens, plant or human toxins, or they could be harmless. Moreover, the
answer will differ for each commercial crop species into which Gene VI has been
Gene VI interferes with host defences
very recent finding, not known to Podevin and du Jardin , is that Gene VI has a second mechanism by which it interferes
with plant anti-pathogen defences , the result is to make plants carrying
Gene VI more susceptible to certain pathogens, and less susceptible to others.
Obviously, this could impact farmers. Furthermore, the discovery of an entirely
new function for gene VI while EFSA’s paper was in press, also makes clear
that a full appraisal of all the likely effects of Gene VI is not currently
Is there a direct human toxicity issue?
When Gene VI is intentionally expressed in transgenic plants, they
become chlorotic (yellow), deformed, and less fertile in a dose-dependent
manner . Plants expressing Gene VI also show gene expression abnormalities.
These results indicate that the protein produced by Gene VI is functioning as a
toxin and is harmful to plants . As the known targets of Gene VI - ribosomes
and gene silencing - are also present in human cells, it is reasonable to be
concerned that the protein produced by Gene VI might be a human toxin. This is a
question that can only be answered by future experiments.
Is Gene VI protein produced in GM crops?
are two aspects to this question. One is the length of Gene VI accidentally
introduced by developers. This appears to vary but most of the 54 approved
transgenes contain the same 528 base pairs of the CaMV 35S promoter sequence, corresponding to approximately the final third of
Gene VI. Deleted fragments of Gene VI are active when expressed in plant cells,
and all functions of Gene VI are believed to reside in this final third.
Thus, there is clear potential for unintended effects if this fragment is
expressed, as some researchers have commented [4, 15, 18].
The second aspect of this question is what quantity
of Gene VI could be produced in GMO crops? This can ultimately only be resolved
by direct quantitative experiments. Nevertheless, we can expect the amount of
Gene VI product will be specific to each independent insertion event. That is
significant Gene VI expression probably would require specific sequences, such as the presence of a gene promoter and an ATG (protein
start codon). Commercial transgenic crop varieties can also contain supernumery copies of the transgene, including
those that are incomplete or rearranged , and those could be important
additional sources of Gene VI protein. The decision of regulators to
allow such multiple and complex insertion events was always highly
questionable, but the realization that the CaMV 35S promoter contains Gene VI
sequences provides yet another reason to believe that complex insertion events
increase the likelihood of a biosafety problem.
direct quantitative measurements of Gene VI protein in individual crop would
not fully resolve the scientific questions, however. No-one knows, for example,
what quantity, location or timing of protein production would be of significance
for risk assessment, and so answers necessary to perform science-based risk
assessment are unlikely to emerge soon.
Big lessons for biotechnology
is perhaps the most basic assumption in all of risk assessment that the
developer of a new product should provide regulators
with accurate information about what is being assessed. Perhaps the next most
basic assumption is that regulators independently verify this information. We
now know, however, that for over twenty years neither of those simple expectations
has been met. Major public universities, biotech multinationals, and government
regulators everywhere, seemed not to have appreciated the possibility that the
DNA constructs they were responsible for could harbour an extra viral gene.
This lapse occurred despite the fact that Gene VI
not truly hidden; the relevant information on the existence of Gene VI has been
freely available in the scientific literature since well before the first
biotech approval in the nucleotide sequence of CaMV published in 1980 . We
ourselves have offered specific warnings that viral sequences could contain
unsuspected genes . The persistent inability of
regulatory risk assessment to incorporate longstanding and repeated scientific
findings is highly worrying; all the more so that this is not an isolated
There exist other examples of commercially approved
viral sequences having overlapping genes that were never subjected to risk
assessment. These include numerous commercial GMOs containing promoter regions
of the closely related virus figwort mosaic virus (FMV)
not considered by Podevin and du Jardin .
Inspection of commercial sequence data shows that the commonly used FMV
promoter overlaps its own Gene VI . A third example is the virus-resistant
potato NewLeaf Plus (RBMT-22-82). This transgene contains approximately 90 % of
the P0 gene of potato leaf roll virus. The known function of this gene, whose
existence was discovered only after US approval, is to inhibit the
anti-pathogen defences of its host . Fortunately, this potato variety was
never actively marketed.
A further key point relates to the biotech industry and
their campaign to secure public approval aided and abetted by a permissive
regulatory environment. This has led to the repeated claim that GMO
technology is precise and predictable; and further, their
own competence and self-interest would prevent them from ever bringing
potentially harmful products to the market, and only well studied and fully
understood transgenes are commercialized. All of these claims have been exposed
to be false in the revelations surrounding Gene VI.
What regulators should do now
Even now that EFSA's own researchers have belatedly considered the
risk, no one can say whether the public has been harmed, though harm appears a
clear scientific possibility. From the perspective of professional and
scientific risk assessment, this situation represents a complete and
catastrophic system failure.
saga of Gene VI is not yet over. We have now carried
out the retrospective risk assessment in full, something that EFSA has failed
to do . We show that the existing data clearly indicate a potential for
significant harm. The only course of action consistent with protecting
the public and respecting the science is for EFSA, and other jurisdictions, to
order a total recall. This recall should also include GMOs containing the FMV
promoter and its own overlapping Gene VI.
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Rory Short Comment left 28th January 2013 18:06:30 This call for a total recall is a logically reasoned one. Unfortunately it conflicts with all sorts of vested interests and is therefore sadly unlikely to happen.The consumer must just stay away from GM foods.
John Fryer Comment left 28th January 2013 20:08:38 JUST DISCOVERED
Virus fragments and bacteria frgaments have been in GMO crops since the inception in 1971.
Professor Robert Pollack complained back then that using bacteria and virus parts in genetic engineering constituted the most dangerous experiment man could ever do.
After a heated argument with the originators of this new technology we finally and more than 40 years on get a glimmer of recognition that this technology is not the same as paleolithic food diets and normal plant breeding methods.
Have EFSA just discovered they have their own brains or will they rely on industry EXPERTS as normal?
David Llewellyn Foster Comment left 9th February 2013 09:09:58 Dr Ho ~ I have just been reading in Forbes, the all guns blazing dismissal by the self-possessed founder of the Genetic Literacy Project , Jon Entine
to whom I addressed the following comment:
As you are such a strong advocate for modified food, I'd be interested in your own diet, and whether you would be prepared to test your confident claims by consuming measured quantities of GMO's for say, a year and monitoring the effects, to document any alleged benefits or evident negative consequences.
Also, I am curious to know why GMO's are so unwelcome in Europe, if the risks as you maintain are so completely negligible. I mean, it is not as though the entire European Union is composed of fanatical anthroposophists.
Rudolph Steiner by the way, who was a student of Goethe, may well have been considered "lunatic" in some people's estimation, but he apparently escaped certification. Be that as it may, I disagree with P L Borst's contention, since Steiner developed his ideas about biodynamics independently, whereas Sir Albert Howard who is generally acknowledged as introducing organic principles to the UK, learned about soil health in India. Should you require more information about these traditional methods, I'm sure you would benefit from Dr Vandana Shiva's expertise.
The British soil association is not composed of lunatics to the best of my knowledge, and I believe some Indians are even thought to be wise.