ISIS has warned against the CaMV 35S promoter and called for all affected GM crops to be withdrawn since 1999 while damning evidence on its safety continues to emerge Dr Mae-Wan Ho
How to bury a bombshell
A European Food Safety Authority (EFSA) scientist has just discovered that major GM crops and products the regulatory agency has been approving for commercial release over the past 20 years contain a potentially dangerous virus gene. The gene – Gene VI – overlaps with the cauliflower mosaic virus (CaMV) 35S promoter. The CaMV 35S promoter is the commonest, most widely used regulatory sequence for driving gene expression in GM crops. This momentous discovery was published in a little known journal during the holiday season at the end of 2012 , and would have passed unnoticed had it not caught the attention of Jonathan Latham and Alison Wilson of Independent Science News. They described the finding and carried out a proper retrospective risk assessment on the Gene VI fragment in a report posted on their website . This attracted so much public attention that EFSA and its counterpart Food Standards Australia New Zealand (FSANZ) are said  to have jointly “shredded” the scientific paper on which Latham and Wilson’s report is based.
EFSA and FSANZ say the allegations that the viral Gene VI hidden in the CaMV 35S promoter might not be safe for human consumption and could disturb the normal functioning of crops are completely false. A spokesperson from FSANZ states: “Human exposure to DNA from the cauliflower mosaic virus and all its protein products through consumption of conventional foods is common and there is no evidence of any adverse health effects.”
Ironically, the first author of the scientific paper  Nancy Podevin is from EFSA, while the second author Patrick Du Jardin is at University of Liège in Belgium; and EFSA GMO Panel is acknowledged for “advice given”. The main thrust of the paper is in fact a screening of Gene Vi amino acid sequence against existing databases for known allergens and finding none; thereby offering false reassurance while the real hazards are swept under the carpet.
This is not the first time that the safety of CaMV 35S promoter is being questioned.
Serious concerns had been raised over the safety of CaMV 35S promoter
ISIS first raised concerns over the CaMV 35S and similar promoters in a paper published in the journal Microbial Ecology in Health and Disease in 1999  (Cauliflower Mosaic Viral Promoter – A Recipe for Disaster?) when it was discovered to have a recombination (fragmentation) hotspot that would enhance unintended horizontal gene transfer and recombination, and in the process create new viruses or activate old ones, and trigger cancer in animal cells by well-known processes of ‘insertion carcinogenesis’. The CaMV 35S promoter was known to be highly promiscuous in being able to function in most if not all species across the living world (including human cells, as it turned out). To make matters worse, many synthetic versions of the promoter have been constructed with additional enhancers for gene expression and sequences from other sources, all of which increase its instability (tendency to fragment) as well as its ability to drive inappropriate gene expression. (We also reported the overlap of the 35S promoter with Gene VI, so this knowledge must have been widely known, although its safety implications were not obvious, at least to us.)
As a precautionary measure, we strongly recommended that all transgenic crops containing CaMV 35S or similar promoters should be immediately withdrawn from commercial production or open field trials.
Our first paper brought a swift reaction. Within two days of its being published online, someone managed to solicit at least nine critiques, including one from Monsanto, which were posted on a website funded by the biotech industry and widely circulated on the internet. The critiques varied in tone from moderately polite to outright abusive. We wrote a detailed rebuttal, which was likewise circulated and posted to the same website, and have not received any replies from our critics since. But in January 2000, Nature Biotechnology published a distorted, one-sided and offensive account of our paper, concentrating on the criticisms and ignoring our rebuttal completely, which we published in the same journal that carried the first paper (Hazards of Transgenic Plants Containing the Cauliflower Mosaic Viral Promoter).
Regulators’ objections irrelevant and false
It is of interest that the objections for ‘shredding’ the scientific paper of Podevin and du Jardin  and Latham and Wilson’s report  are exactly the ones used against us. The first objection is that humans have been eating the CaMV for millennia without ill effects; the second is that the CaMV 35S promoter is only active in plants and certainly not in animal or human cells.
Our rebuttal to the first objection is that the intact CaMV, consisting of the CaMV genome wrapped in its protein coat, is not infectious for human beings or for other non-susceptible animals and plants, as is well-known; for it is the coat that determines host susceptibility in the first instance. So eating the intact virus is of little consequence. However, the naked or free viral genomes (and parts thereof) are known to be more infectious and have a wider host-range than the intact virus. Furthermore, the synthetic CaMV 35S promoters are very different from the natural promoters, and are both much more aggressive as promoters driving inappropriate gene expression as well as more prone to fragment and recombine.
The second objection – that CaMV 35S is not active in animals and human cells – is simply false as we discovered in the scientific literature dating back to 1989, and pointed this out in a third paper  (CaMV 35S promoter fragmentation hotspot confirmed, and it is active in animals ). The CaMV 35S promoter was found to support high levels of reporter gene expression in mature Xenopus oocytes , and to give very efficient transcription in extracts of nuclei from HeLa cells (a human cell line) .
What of our original concern over the CaMV 35S promoter activating viruses in host genomes? There is new evidence suggesting that the CaMV 35S promoter may indeed enhance the multiplication of disease-associated viruses including HIV and cytomegalovirus through the induction of proteins required for transcription of the viruses  (New Evidence Links CaMV 35S Promoter to HIV Transcription).
It is in this context that Latham and Wilson’s report for ISIS  (Potentially Dangerous Virus Gene Hidden in Commercial GM Crops, SiS 57) should be read, which fully justifies our original recommendation for a total recall of the affected GM crops. This same call is now repeated by Latham and Wilson.
1. Podevin N and du Jardin P. Possible consequences of the overlap between the CaMV 35S promoter regions in plant transformation vectors used and the viral gene VI in transgenic plants. GM Crops and Food 2012, 3, 1-5.
2. Latham J and Wilson A. Regulators discover a hidden viral gene in commercial GMO crops, Independent Science News 21 January 2013, http://independentsciencenews.org/commentaries/regulators-discover-a-hidden-viral-gene-in-commercial-gmo-crops/
3. “Alarming GM study shredded by authorities”, Kondinin Group, 24 January 2013, http://www.kondiningroup.com.au/StoryView.asp?sectionsource=s1450060&StoryID=795111855
4. Ho MW, Ryan A, Cummins J. Cauliflower mosaic viral promoter – a recipe for disaster? Microb Ecol Health Dis 1999, 11, 194–7.
5. Ho MW, Ryan A, Cummins J. Hazards of transgenic plants with the cauliflower mosaic viral promoter. Microb Ecol Health Dis 2000, 12, 6–11.
6. Ho MW, Ryan A, Cummins J. CaMV35S promoter fragmentation hotspot confi rmed and it is active in animals. Microb Ecol Health Dis 2000, 12, 189.
7. Ballas N, Broido S, Soreq H, Loyter A. Efficient functioning of plant promoters and poly(A) sites in Xenopus oocytes. Nucl Acids Res 1989, 17, 7891–903.
8. Burke C, Yu XB, Marchitelli L, Davis EA, Ackerman S. Transcription factor IIA of wheat and human function similarly with plant and animal viral promoters. Nucleic Acids Res 1990, 18, 3611–20.
9. Ho MW and Cummins J. New evidence links CaMV 35S promoter to HIV transcription. Microb Ecol Health Dis 2009, 21, 172-4.
10. Latham J and Wilson A. Potentially dangerous virus gene hidden in commercial GM crops. Science in Society 57 (to appear).
SOURCE – ISIS