Monday, January 7, 2008

GM Maize Approved on Bad Science

ISIS Report
February 26, 2002

A four-hour public hearing on Aventis T25 GM maize left no doubt that its market approval was a scientific sham from beginning to end. Dr. Mae-Wan Ho reports.

The small room was filled to capacity, with several rows of seats in the front reserved for Aventis. I had to sit almost halfway to the back, even though I was told the front rows were reserved for witnesses.

The hearing was hastily put together. Very few groups knew about the event, and even fewer invited to present evidence or to attend. Despite that, people were drawn from all over the country, as far away as Wales and Scotland.

Fourteen witnesses were to speak for five minute each, over five sessions: horizontal gene transfer and gene stability, environment risk assessment and monitoring, compositional equivalence, feed safety assessment, and chicken feeding study. "Aventis Crop Science Ltd" was listed five times, and two further witnesses were also speaking for the company. The odds were clearly stacked in Aventis favour

In addition, four specialists were invited to comment on the evidence presented. No questions or comments were allowed from the floor. The objectors were placed at considerable disadvantage. A spokesperson of Friends of the Earth tried to raise objections to procedure, but was firmed quashed by the chairperson, Professor Alan Gray.

Gray stated categorically that only scientific evidence was to be considered, and nothing on the social ethical implications. That was enough to show up the fallacious belief, endemic to the scientific establishment, that ethics and social responsibility are divorced from science. C.P. Snow called that "the moral trap" back in the 1960s, as it enables scientists to abdicate responsibility for their research.

Nevertheless, as soon as the proceedings began, it became evident that even within the narrow interpretation of science, Aventis and ACRE both failed miserably to pass muster. Scientific evidence piled up against their ignorance and denial, and the more Aventis spoke, the deeper it dug itself into a hole. Half-way through, Aventis already had to admit they have to "take new evidence on board".

According to the agenda circulated just the day before, I was to be the first witness. But, without any warning, Dr, Ricarda Steinbrecher (Econexus) was asked to go first instead.

Slightly unsettled but remaining calm, Ricarda exposed the ignorance of the EU Scientific Committee on Plants, ultimately responsible for approving T25 under the old Directive on deliberate release. The Committee had assumed that the cauliflower mosaic virus (CaMV) 35S promoter driving the expression of the pat gene for glufosinate tolerance, was not active in bacteria, and so it would not matter even if the gene were taken up by bacteria. In fact, CaMV 35S promoter has been known to be active in bacteria since 1990. This mistake was repeated in Aventis submission to this open hearing.

The pat gene is from a specific strain of Streptomyes viridochromogenes, originally isolated from Cameroon. The gene is not at all widespread among Streptomyces or other soil bacteria in Europe, as Aventis claimed. It codes for an enzyme that transfers an acetyl group to glufosinate, thereby detoxifying it in the plant. However, as with most enzymes, it catalyses also the reverse reaction. (Elementary chemistry tells us that all chemical reactions are in principle reversible, depending on the concentrations of the reactants and the products.)

Cows feeding on T25 maize will have lots of bacteria in their stomachs and plenty of opportunity to take up the pat gene. These bacteria will then be able to remove the acetyl group from acetyl-glufosinate, thereby turning it back to glufosinate. The herbicide is known to be poisonous to mammals including human beings, causing birth defects and damaging nerve cells. What the pat gene will do in the soil will be anybody s guess. Glufosinate also harms mites, caterpillars and other insects (reviewed in Petition to Scottish Parliament in support of Munlochy Vigil by Mae-Wan Ho, to be available

I pointed out that not only is the CaMV 35S promoter active in bacteria, it is active across the entire living world, including frog eggs and human cells, as Ho, Ryan and Cummins had detailed in a series of scientific papers published between 1999 and 2000. The two experts invited to speak afterwards admitted they were "not familiar" with those findings, just like other experts we had to deal with in the past.

Worst of all, there is no evidence T25 is genetically stable, I said. Genetic stability is the single most important criterion for approval, before one even considers environmental and health risk assessment. The previous public hearing on T25 was suspended more than a year ago when it was found not to have passed the then required EC test for distinctiveness, uniformity and stability.

The new EC Directive requires strict molecular evidence, event specific molecular evidence, I stressed, revealing where in the genome each insert is located, and in what form, for at least 5 successive generations.

Regulators have never required that kind of molecular data in the past. Instead, they accepted so-called mendelian inheritance . This was another scientific fallacy working to favour industry. Failure to depart from mendelian ratio, as every good scientist should know, is not evidence of mendelian inheritance, much less is it of genetic stability, especially when the genotype of the parents are not independently ascertained. Aventis has even got the wrong mendelian ratios in some of the documents submitted for the UK field trials. The company conceded that mendelian ratios were not evidence of stability.

Transgenic instability, especially structural instability, was itself a safety concern, as it increases the chance of horizontal gene transfer and recombination.

Horizontal gene transfer is not just a theoretical possibility. It has long been known to happen in the laboratory and in microcosm experiments. Given that, we should be demanding proof that it does not occur in the field. Instead, the attitude has been, "just because it happens in the laboratory doesn t mean it happens in the field". And when German scientists found evidence that it has occurred in the field, ACRE interpreted the evidence selectively, contradicting both good science and the precautionary principle, which I consider one and the same thing.

I then elaborated on why we have to worry about eating transgenic DNA and not natural DNA. In many senses, transgenic DNA is optimised to spread by horizontal gene transfer and to invade the genome of cells from bacteria to human beings. (see "The best kept secret of GM crops", ISIS report, February 14, 2002 ).

The experts, Professor JPW Young (Univ. of York microbial geneticist) and Professor Heslop-Harrison (University of Leicester, genome stability) stated that horizontal gene transfer would depend on selection pressure . When asked if transgenes would be more unstable, Heslop-Harrison replied that natural genomes are unstable anyway, at "much lower frequency", though more so in tissue culture.

Unfortunately, I was prevented from pointing out the bad science involved in the argument that "horizontal gene transfer happens only under strong selection pressure". The "selection" refers to the use of antibiotics to select for antibiotic resistance. The antibiotic is applied after horizontal gene transfer and recombination has taken place, to enable the experimenter to selectively pick out the recombinants carrying the antibiotic resistance gene. It is "selective seeing", and not selection on the processes of horizontal gene transfer and recombination that have gone on before.

Horizontal gene transfer is really an anti-selection process: different species are sharing their most valuable assets for survival in the presence of antibiotics. In fact, there is already evidence that the presence of antibiotics increases the frequency of horizontal gene transfer 10 to 10 000 fold. When will biologists stop allowing natural selection to cloud their logical faculties and to confuse the public?

In the same vein, industry claims that it is the overuse of antibiotics in agriculture and medicine that s causing the spread of antibiotic resistance, so everything will be fine when antibiotics are phased out. There is now a substantial body of evidence on antibiotic resistance persisting indefinitely after the antibiotics are phased out. It is the complexity and entanglement of gene functions which, time and again, defies simplistic predictions (see "Phasing out antibiotics will not reduce antibiotic resistance" by Mae-Wan Ho, ISIS News 6, September 2000

The objectors went from strength to strength. But awkward questions also came from certain members of ACRE. Prof. Chris Pollock demanded to know about post-release monitoring. How was the information collected? What sort of monitoring and record keeping? What is the significant change? To none of which Aventis could reply. Agronomic performance was all. Another member of ACRE asked. Were soil microorganisms looked at? When Aventis stated there was no difference in wildlife, which species and which pests were recorded? Aventis answered that the data was "from USA".

Dr. Sue Mayer (GeneWatch) was scathing about the risk assessment, which would not be accepted today, as it did not include environment assessment, monitoring plan, impact on animal health and food chain. Numerous bland assertions of "no difference" or "no impact" were not backed up by hard data. On that basis, ACRE approved the farm scale evaluations back in 1996. And there is still no sign that ACRE has taken the new principles on board.

During the questioning, Pollock suddenly declared that the farm scale evaluations were not a test of GMOs, only the agronomy of introducing new herbicide regime. That was news to all present. But we could not follow that up, and ACRE must tell us the truth. If Pollock is right, then there is not a whiff of a case for even contemplating the market approval of T25, the reason ACRE organised this public hearing.

On compositional equivalence, Dr. Vyvyan Howard (University of Liverpool, toxicologist) pointed out that statistically significant differences were in fact found between the GM and non-GM varieties, some of which went outside the range for all varieties, and still they were ignored and considered substantially equivalent . And feeding tests based on the purified protein from bacteria fed to rats have got nothing to do with the entire GM plant being consumed by cattle as intended. Compositional equivalence is a chemical test and says nothing about the biological risks.

Professor Richard Phipps defended substantial equivalence based on compositional equivalence. Mysteriously the data he used were quite different from those originally submitted by Aventis, which Vyvyan Howard had criticised. Phipps rationale was that, as the compositional comparisons revealed the GM was substantially equivalent to non-GM, then the only difference must be the gene product itself, hence, studies were carried out using the purified protein. So the use of substantial equivalence is to provide justification for the absurdly reductionist approach in risk assessment. It ignored all interactions between genes, proteins, metabolites, whatsoever.

Gross chemical analyses are the least discerning tests in the first instance, and all proteins will have roughly the same amino acid compositions, especially on the average. Ho and Steinbrecher have pointed that out in a scientific paper published in 1998, demanding protein and other molecular profiling, at the very least.

Aventis was subjected to some sharp questioning. What is the extent of the data? Were the data for a particular year, or over several years? And why were the data different from those Vyvyan Howard used? What value was compositional equivalence for safety? Aventis had no answer to any of the questions, and had to admit compositional equivalence was "not indication of safety", and that "new evidence had to be taken on board".

On food safety assessment, Prof. Bob Orskov (Macaulay Institute, specialising in nutrition of ruminants), was in no doubt that "chemical analysis means nothing in relation to safety of milk of dairy cows". "When feeding ruminants we are feeding bacteria," he said. There is no research on that. "It was such an easy thing to do, but none asked to do it. Should I be convinced to drink the milk?" he asked. "We are in no hurry. We should do the microbial trials in the lab first, then do feeding trials, and look at the milk. Lots of background work must be done first."

A spokesperson for ACRE pointed out that chemical analysis has always been used to characterise new feedstuff. But that is hardly appropriate for GM feedstuff. It exposes the basic, erroneous a priori assumption that there is no difference between GM and non- GM. In any case, Orskov pointed out that it was the chemical composition of forage and not grain that should have been analysed.

Chris Pollock asked whether he was aware that studies on microbes that "throw up anomalies" that could not be predicted from chemical composition. Yes, digestibility of cellulose, for example. Some cellulose have more side branches and much less easy to digest.

Prof. David Beever (University of Reading) spoke on behalf of Aventis, to convince us that DNA is broken down during commercial processing and there was nothing to worry about. He misrepresented the MAFF-funded study, which showed in fact that most commercial processing left DNA either intact or incompletely degraded, and specifically recommended against feeding GM silage to farm animals (ISIS Report, Transgenic DNA in Animal Feed; also in Horizontal gene transfer, ISIS reprints, 2002). When asked by Janet Bainbridge whether there should be routine testing for transgenic DNA in animal products, Beever predictably said it would be a waste of time.

Emily Diamand and Adrian Bebb (FoE) further attacked ACRE for taking a cavalier attitude towards safety, against the advice of key scientists of the Advisory Committee for Novel Food Products (ACNFP). They objected that the feeding trials were done on non-target species, ie, rats and chickens instead of cattle. Bainbridge of ACNFP said they have "revisited issues" since and will be posting the results on their website.

Finally, Dr. Toby Knowles (University of Bristol, statistician) laid into Aventis chicken feeding studies in which twice as many chickens died from eating GM as non-GM maize: "flawed design", "science substandard", "not evidence of anything". He would definitely have rejected it for publication. Those views were generally shared by Professor Stephen Senn (University College, London, statistics consultant for pharmaceuticals), though he would not be surprised if the study were accepted for publication, given that "the standard of statistics in science is very dubious" in general. That is certainly true of papers in the GM area, and there are deeper questions on the burden of proof and hypothesis testing (See " "Use and abuse of the precautionary principle" by Peter Saunders, ISIS News 6, September 2000; also in The Precautionary Principle, ISIS Reprints, Peter Saunders and Mae-Wan Ho, 2002).

Disappointingly, neither statistician would be drawn on the question as to whether the precautionary approach would require a different use of statistics. I should have asked them whether they would eat the GM maize or cattle fed from GM maize.

An ex-president of the Royal Statistical Society had remarked that in the matter of safety, even one dead rat should raise concern. If so, should we at least re-set the level of statistical significance, at 10% or even higher rather than 5%? It would certainly save inflicting undue suffering on animals as well.

ACRE has promised to put up their report of the meeting and the papers submitted on their website.

This article can be found on the I-SIS website at

No comments: