Ignoring the genomic mess we're creating with GM

April 2011

In April 2005, an American opinion was published in the scientific literature stating that genomic characteristics need no longer be considered by regulators.

A team from the biotech industry and US universities suggested that, to regulate GM crops “sensibly”, the present impediments posed by costly restrictions and requirements could now be safely “modified”. The team argued that we now have “long-accepted” breeding methods, “two decades” of “experience”, an “expanding knowledge of the plant genome,” and indications that the “genetic engineering process itself presents little potential for (unidentified) unexpected consequences”. Therefore, it was reasoned that regulatory oversight need only focus on standard agricultural practice in use plus the nature of the introduced genes.

No doubt stimulated by the above paper's claim that GM crops face a “daunting” array of regulatory requirements in a country (the USA) where the safety testing is, in fact, largely voluntary, David Schubert, a Professor of Cellular Neurobiology in the Salk Institute in California, was moved to submit a strong rebuke to it which was published in July 2005.

Schubert pointed out that the use of chemicals and radiation to generate random mutations in crop plants, which is often cited as a reason why genetic transformation is just an extension of conventional breeding, has been outmoded for about half a century. Modern plant breeds are produced by merging whole chromosomes of diverse plants and, therefore, have sets of genes which are still maintained within their natural context. In other words, there are NO mutations induced in them.

This is an important point. The added, man-made, DNA includes a whole concoction of out-of-context sections, including genes, on/off switches, stimulators, synthetic linkages and sometimes spurious DNA from no-one-knows-where, each of which represents a mutation whose effects may extend beyond the construct.

And worse, the novel construct isn't the only mutation induced in a GM plant. The process of insertion is known to induce other mutations in the plants' own DNA. These can include, not only small alterations in the building blocks of the DNA, but also more major changes such as scrambling, deletions, additions, and activation of dormant 'mobile elements' which then, themselves, become mutagenic. Besides the possibility of conferring physiological weaknesses in the plant and anti-nutritional elements in our food, such random and extensive mutations might effects the plants' normal accumulation of thousands of phytonutrients. These small molecules form a vital part of the plants' immune system to deal with environmental stresses. They are highly biologically active, and could, therefore, become toxic if their structure and metabolism is inappropriately altered by mutated DNA.

Rather than de-regulation of transgenic crops, the Professor suggests further important, up-to-date safety tests. These include metabolic profiling to detect unexpected changes in small molecules, a specific test for the presence of mutagens, multi-generation feeding studies, and rigorous allergenicity testing.

In August 2005, a technical report was published in the scientific literature describing an investigation into an unexpected feature of GM maize. Two commercial Bt-toxin inserted varieties were compared with their closest non-Bt maize relatives. Measurements were made of the quantity and composition of the lignin (the fibrous woody material which gives plant tissue its strength) in the stems and leaves of the plants. Three important findings emerged:
  • the stems of the GM maize had 18.2% more lignin;
  • the molecular composition of the lignin was significantly different in GM varieties;
  • the quantity and quality of lignin in the leaves, however, were not different.
Clearly, these alterations in lignin did not impair the commercial value of the maize, but the study raises a number of questions:
- This report was in fact the second such finding of disturbed lignin formation in a GM plant, but the previous one was in a completely different type of plant (a soya bean) which had an entirely different type of gene inserted (one for herbicide tolerance). Coincidence? Or, is there some common disturbing factor, such as an immunological response, operating in transgenic plants?
  • The observed differences only emerged after commercialisation because new and more sophisticated techniques were used in place of established methods. Is the current technology used to assess GM crops telling us what we need to know, or is its crudeness allowing the biotech industry and regulators to gloss over potential problems they'd rather not notice?
  • The alterations in lignin molecular structure and the observed qualitative and quantitative links to specific plant tissues suggest that complex changes in the expression and interaction of a large number of genes are involved. What are the implications of these changes for food safety and the environment; for example, is the microbial life associated with such distorted GM material likely to be altered?

Professor Schubert's concerns seem to be backed up by such evidence, and the reasons given to support the opinion aimed at deregulation of GM crops ring a little hollow.

At the end of 2005, an even more disturbing Review Article of the evidence for 'The Mutational Consequences of Plant Transformation' was accepted by the scientific press.

A British team reviewed all the published work they could find documenting DNA changes in GM plants. They found seven in the run-up to GM commercialisation in 1996, and an average of five per year since. The most studied plant species are Arabdopsis (a simple plant, much studied by scientists for this reason, but not eaten) and rice (barely starting to be commercialised at the time of the writing).

The Review examined the effects of the two major mechanisms for inserting DNA into crops.

One such method uses an infectious microbial vector, Agrobacterium, to carry the DNA into plant cells growing in tissue culture. The authors note that: Agrobacterium infection itself is known to be mutagenic; cells forced to grow outside their natural context as in tissue culture are known to mutate easily; antibiotics (a necessary part of tissue culture) also are known to cause mutations. In other words, even without the addition of engineered DNA, extensive genome-wide mutations will arise due to the cell manipulations employed. Plant transformation procedures were found, typically, to introduce many hundreds to thousands of genome-wide mutations into the plant, amounting to a 2-4% reduction in genomic similarity compared with the parent type. Besides affecting the safety and performance of GM crops in a totally unpredictable manner, they will interfere extensively with the results, interpretation and usefulness of scientific experiments on GM plants.

The second means of inserting DNA is to coat metal particles with many copies of the novel construct and fire them into the genome until some DNA sticks. This procedure was always found to be associated with genome disruption, rearrangements and the presence of superfluous multiple copies of DNA. However, very few studies have been made of the mutational effects of this method, and since these few studies have been on specially selected 'simple' events, the true extent of DNA disruption may be considerably more than that reported so far.

The study notes that, besides the induced mutations, transgene insertion can have complex effects on the host DNA function, including the silencing of whole groups of genes and mis-reading of DNA. It also raises the concern that, after insertion of bacterial DNA into a plant, the incidence of horizontal gene transfer between the plant and other bacteria with similar DNA may be significantly elevated.

The paper concludes by suggesting that, if we want to continue to insert DNA into our crop plants, we must first of all learn to do it with precision and find a way which doesn't disrupt the genome beyond the inserted construct. Suggestions for a more sensible approach include:
  • tissue culture must be eliminated from the procedure
  • DNA insertion must be targeted, not random
  • alternative methods must be developed which eliminate the presence of superfluous, non-gene DNA and chromosomal damage.
  • effective back-crossing must be done to dilute out unwanted side-effects.

There are several additional very disturbing aspects to these papers.

The biotech industry is showing every signs of a PR drive to remove irritating regulations on GM. Its claims about our 'expanding knowledge' and long 'experience' are not backed up by science: very few publishable studies are in evidence; its own work has not been thrown open to scrutiny; and there is no reason to believe it has ever taken a thorough look at what it has created.

Despite the huge numbers of GM plants generated in laboratories using a host of different transformation events, and their widespread presence in the American food chain, the extent of DNA disruption has not been documented. Neither is the ubiquitous presence of mutations being acknowledged by the biotech industry, by its scientists, nor by our regulators. Only a handful of the studies done refer to plants we are actually expected to eat.

There is every sign that the biotech industry is being allowed to have all its own way by regulators. For example:
  • The insistence that all GM crops be assessed on a 'case-by-case' basis is a good way to avoid connecting any problems common to all transgenic plants.
  • The use of out-dated methodology, which became 'established' before GM days and was developed for a different purpose, is used to conceal the abnormalities emerging.
  • As soon as man-made DNA is randomly inserted, correct scientific protocol becomes impossible: there simply is no plant which is genetically the same but minus the extra DNA to use as a control in experiments. The biotech industry, with regulatory approval, has slipped in the concept of “substantial equivalence” to get around this problem. Just how meaningless this concept is, is revealed quite clearly in Prof. Schubert's rebuke and the Review of mutational consequences of GM.

The most grim implication of the genomic mess created might be long-term genetic instability of GM plants with their widespread mutations and re-mobilised mutational elements. This could well mean that last year's crop which was proven safe might not be the same as this year's crop which you are eating. And the enormous question of how these mutations might evolve outside of our neatly sterilised fields once they become part of weedy plants, or when they are absorbed into microbial life in the soil, is anyone's guess.

(Adapted from an article which appeared in the GM-free Scotland website in April 2006)

Sources:
  • David Schubert, Sensible Regulations for GE Food Crops, Nature Biotechnology, July 2005, 23
  • J. R. Latham, A. K. Wilson, R. A. Steinbrecher, 2006, The Mutational Consequences of Plant Transformation: Review Article, Journal of Biomedicine and Biotechnology, ID 25376
  • J. Poerschmanna et al., 2004, Molecular composition of leaves and stems of genetically modified Bt and near-isogenic non-Bt maize', http://jeq.scijournals.org/cgi/content/abstract/34/5/1508 August

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