Changing models of the genome

April 2011

Twenty years ago, when genetic engineering was in its infancy, and commercialisation of a genetically tranformed plants no more than a dream, genes were viewed as fixed units of DNA embedded in swathes of 'junk' DNA.

The genes in this out-dated model could be relied upon to reel off messenger molecules of RNA which trotted out into the cell, where they ordered the production of specific proteins. In this scheme, each gene was an active stretch of DNA coding for its own protein, while the rest was inert padding. In food, the model predicted that all DNA was quickly broken down by the digestive processes, while RNA was so unstable it would disappear long before it got that far.

This model was, and remains, that on which GM crops are based and on which their safety-testing has been formatted ever since.

Unfortunately, the model is becoming increasingly shaky: genes are now appreciated as variable parts of a fluid system of DNA which can adjust its final expression minutely; 'junk' DNA is highly active and sends out RNA messengers of its own which exert a finely-tuned control over what happens in the cell; in food, DNA can survive intact through a large part of the gastrointestinal tract; and in the organism, RNA it seems can sally forth in stabilised forms. Both RNA and DNA are now suspected to have a function outside of the cell: a function which may be vital to both cellular communication and the coherent functioning of the whole organism.

The implications of this much more complex and interactive picture are extensive.

For the GM plant, the three or four artificial genes inserted amongst thousands of natural genes and affecting a negligibly small part of the cell's protein-production mechanism, are now seen to be a bulldozer. The artificial insert cuts through the life processes at all levels. Not only are the interactions of plant's natural genes disturbed, but also those of its 'junk' DNA, its RNA, its cellular proteins, and even the cells of the entire organism.

Because the DNA construct and the genome around it seem inevitably to become scrambled during insertion, extra sections of DNA are found scattered around the host nucleus. These may be bits of artificial DNA, bits of the host plant's DNA, bits of bacterial DNA acquired during propagation of the construct in E. coli bacteria prior to insertion, or completely unidentifiable DNA sequences from who knows what source. Such rogue DNA nevertheless can produce rogue RNA whose action can't be determined, but whose ability to interfere with the other regulatory RNA leading to disruption of the cell is certainly possible.

For the consumer of GM food, the presence of DNA or RNA fragments in partially-digested food may be far from benign. Bacterial and viral DNA are known to be a major factor in stimulating the immune (inflammatory) response to infections, and at least one example of RNA allergenicity is recognised.

All GM crops so far commercialised have had bacterial DNA inserted, and most include viral DNA as well. Although these have been engineered to make them plant-like (or they wouldn't be expressed by the GM plant), the possibility of them retaining properties which induce inflammatory reactions in our gut has never been investigated. Add to that, bacterial DNA can become complexed to other materials enhancing its immuno-stimulatory ability.

Some forms of natural bacterial DNA (much beloved by yoghurt manufacturers) have a probiotic effect which protects the digestive tract against inflammation, but there's no reason to assume novel bacterial-plant DNA can't do the opposite and induce inflammation or, indeed, disrupt the protective effects of the probiotic material present.

There has been some debate over whether transgenic DNA can end up in milk: studies have failed to find novel DNA in milk from cows fed GM feed. However, one Italian survey identified GM maize DNA in 25% of samples of milk on sale and GM soya DNA in 11.7% of the samples. This novel DNA seems to have derived from environmental debris.

For the microbial life exposed to GM DNA in our mouth and gut, there are fine opportunities to acquire and swap interestingly useful bits of novel DNA, such as antibiotic resistance and toxin genes. The presence of bacterial DNA, even if its thinly disguised as a plant, can carry other DNA, piggyback-fashion, into the microbe. This is not just a theoretical possibility, science has demonstrated such transfers of DNA into microbial flora in both livestock and humans.

Up until now, the European Food Safety Authority (EFSA) has confined its risk assessments to the artificial gene in isolation, the artificial protein it generates in isolation, and the undefined quality of 'substantial equivalence' between the GM crop and an undefined comparator crop.

This regulatory tunnel-vision is further narrowed by the assumption that the novel DNA could only cause a problem if it remains in the form of a whole gene and has the opportunity to express its novel protein: the potential for roving small fragments of DNA in the GM plant, in the consumer or in microbes associated with either of these, to cause genomic disturbances or produce RNA which interferes with cellular function is not considered. A particularly large regulatory blind spot seems to exist regarding the powerful viral DNA promoters which don't code for proteins but can induce many types of DNA to 'switch on'. As has been demonstrated by the disappearance during insertion of a very long section of the enhancer-duplicated cauliflower mosaic virus promoter from the Roundup Ready soya herbicide-tolerance gene, the viral promoter certainly needn't be complete to function

The interactions between the novel and the natural genome, between the novel and natural RNA, and between the novel protein and the cell around it, are smoothed out by the iron of 'substantial equivalence'. The use of 'equivalence' instead of accepted statistics which would indicated significant, or no significant, differences in the GM material is an admission that differences are inevitable in GM plants, but can't be regulated without applying an arbitrary decision that significant differences don't impinge on safety.

(This article is adapted from an article which first appeared on GM-free Scotland in March 2010. View an archived copy of that article here.)

Sources

• Werner Műller, Effect of foreign DNA/RNA on the Human Immune System in regard to Genetically Modified Plants,Environment Protection Organisation, Global 2000, Vienna, 2007
• Intercommunication via Circulating Nucleic Acids, Institute of Science in Society Report, 20.04.09
• Netherwood et al., 2004, Assessing the survival of transgenic plant DNA in the human gastrointestinal tract, Nature Biotechnology 22:2
• Yew and Cheng, 2004, Reducing the immunostimulatory activity of CpG-containing plasmid DNA vectors for non-viral gene therapy, Expert Opinion on Drug Delivery 1(1)
• Obermeier et al., 2003, Contrasting activity of cytosin-guanosin dinucleotide oligonucleotides in mice with experimental colitis, Clinical and Experimental Immunology, 134u
• `Agodi, et al., 2006, Detection of genetically modified DNA sequences in milk form The Italian market, International Journal of Hygiene and Environmental Health 209
• Phipps, et al., 2003, Detection of Transgenic and Endogenous Plant DNA in Rumen Fluid, Duodenal Digesta, Milk, Blood, and Feces of Lactating Dairy Cows, Journal of Dairy Science, 86
• Einspanier et al, 2001, The fate of forage plant DNA in farm animals: a collaborative case-study investigation cattle and chicken fed recombinant plant material, European Food Research Tchology, 212
• Professor Jack Heinemann, Report on animals exposed to GM ingredients in animal feed, prepared for the Commerce Commission of New Zealand, 24.07.09
• Professor G. Wenzel, 2008, The experience of the ZKBS for risk assessment of soybean, Journal of Consumer Protection and Food Safety, 3 Supplement 2