The Institute of Science in Society
http://www.i-sis.org.uk

"Sidesteps fundamental criticisms of GM technology", "fails to take the full range of scientific evidence into account", "riddled with misrepresentations, half-truths and worse". ISIS rejects UK Government's GM Science Review. Dr. Mae-Wan Ho reports.

Commercialisation by Stealth
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The GM Science Review, perhaps the most important of the three strands in UK's public 'consultation' on GM, released its First Report in July 2003 amid accusations of pro-GM bias. One member of the review panel resigned because of pressures on him to toe the pro-biotech line, and another complained that attempts had been made to undermine his research funding and career prospects (see "Dirty works in UK's GM Science Review", this series).

The most serious shortcoming of the GM Science Review is that it entirely ignores the substantial body of evidence on the proven successes and benefits of organic farming, agroecology and other forms of sustainable agriculture. Not even to consider these, while dealing at length with the projected potential benefits of GM is to restrict the scope of the debate from the very outset.

At first glance, the Report looks reasonable enough. Chapters 5, 6 and 7, each 50 pages long, claim to address all the objections that critics have raised on health and environmental impacts and gene flow from GM to non-GM crops and wild weedy relatives. They contain sections with such promising titles as, "Possible nutritional toxicological differences in GM food", "Food allergies for GM crops", "The fate of transgenic DNA", "The effect of GM-derived feed in the food chain", "Invasiveness/persistence of GM plants", "Toxicity to wildlife", "Can DNA from GM crops transfer to soil microbes?" and "Can genetic material in GM plant transfer to viruses?"

But the promise the headings is not fulfilled by the contents. No one can be surprised that the industry-dominated review panel found no evidence that GM crops pose a threat to health or the environment, as widely reported in the media. The precise wording (p.10), however, is full of qualification and equivocation, and this runs through the entire report: "To date there have been no verifiable untoward toxic or nutritionally deleterious effects resulting from the cultivation and consumption of products from GM crops. However, absence of readily observable adverse effects does not mean that these can be completely ruled out and there has been no epidemiological monitoring of those consuming GM foods."

The Review does not give blanket approval for growing GM crops in Britain. Instead, it recommends that each application for approval should be considered and assessed for risks on its own merits. This may sound reassuring, but in fact it is not. For the "case by case" approach that is being advocated is based on the unsupported assumption that there is nothing wrong with GM technology in general. The most that is being investigated is whether any particular crop presents specific hazards.

At no point are the important and fundamental issues addressed. Worse, each application that is approved serves as a precedent for approving later ones, and in the end, it will be claimed that the entire technology has been properly investigated and approved when in fact it was never investigated at all.

And sure enough, the Review states openly (p24) that the "appropriate agriculture for the UK" would be, among other things, one that would "allow coexistence of farming systems." In other words, the Review clearly accepts from the outset and the principle that GM crops based on current technology should be grown in Britain - which is precisely the point that they were supposed to be deciding. The only question is whether some individual crops might be excluded.

The "case by case" approach is thus a slowly-but-surely tactic for commercial approval of GM crops.

We are given plenty of false reassurances - repeated with monotonous regularity at the end of every subsection. It goes like this.

"Is there general scientific agreement?" Yes, generally, after paragraphs riddled with equivocation, misrepresentation, omission, half-truths and worse, that the risk from eating GM food, horizontal transfer of transgenic DNA, or of allergy, toxicity, cross-pollination, whatever, is very low, as the perceived hazard is very rare, if it happens at all.

"Is the issue unique to GM?" No, not at all, or not in many cases, or not usually.

"Are there gaps in our knowledge or scientific uncertainties and are they important?" Yes and no. We should proceed with caution on a "case by case" basis.

"Likely future developments"? Looks good if not great, they will overcome the uncertainties and bring many potential benefits. At one point (pp74-77), the Report even promises "safer, nutritionally enhanced" GM foods, including "golden mustard" as follow-on from "golden rice", supposedly to cure vitamin A deficiency in the Third World, and failing to mention that "golden rice" has already been widely exposed to be worthless. Many kilograms of the rice would have to be consumed each day to get the minimum daily requirement of vitamin A, while leafy greens that can be grown in every backyard would provide a much richer source of the vitamin plus other essential vitamins, minerals and micronutrients.

"Where there is important scientific uncertainty, what is the way forward?" Research and more research, and regulation, with "cautious commercial approval" and "post-release monitoring" and yes again, a "case by case" approach.

The "case by case" approach is not just a tactic for commercialising GM crops. It is also a subterfuge for sidestepping fundamental criticisms of the GM technology itself, which the Report has singularly failed to acknowledge. In other words, it has given blanket approval for GM technology, which can only be justified by ignoring critical scientific evidence.

Some of the most powerful critics - the two dozen prominent scientists who have constituted themselves as an Independent Science Panel (ISP) on GM who oppose the official GM Science Review - are saying that the GM technology is inherently unsafe, that the hazards are unique to GM, and that the evidence, incomplete though it is, already supports that view, but is being obfuscated, suppressed, or otherwise not addressed by the pro-GM establishment.

To have a useful, informed debate, the key areas of scientific disagreement must be clearly laid out before the public, as is done in the ISP Report, The Case for a GM-Free Sustainable World, released on June 15, 2003 (http://www.indsp.org/), which includes extensive review of the evidence on the successes and benefits of non-GM sustainable agriculture as well as the many problems and hazards of GM crops. The ISP Report, widely adopted by civil society organisations in Britain and around the world, was submitted to the GM Science Review, but it has neither been acknowledged nor posted on the official website. Our closely argued case as a whole also remains to be answered.

It will be instructive to give some glaring examples of how the Report sidesteps the major scientific criticisms in its attempt to ultimately mislead and cajole the public into accepting the commercialisation of GM crops.

Evidence that GM is inherently unsafe remains unanswered 1. GM is distinct from conventional breeding methods, including mutations induced by X-rays or chemicals. It is unreliable, uncontrollable, unpredictable and unstable; and introduces new risks (see below).

It is not just the rate of success that is at issue. To say that the rate of success in conventional breeding is no better than for GM (pp.9, 49, 52) is not an answer to the genetic instability unique to GM lines that comes from the GM technology itself. Making a GM plant or animal involves breaking and joining the DNA of the host genome at many unspecifiable locations, a process referred to as "illegitimate recombination", which distinguishes GM from all conventional methods. This process leads to substantial scrambling of both foreign and host DNA at the sites of integration.

Moreover, even the 'successes' in GM are unstable, and prone to further changes. These changes include silencing of the foreign genes, further rearrangement of the DNA and loss of the genetic material, all of which are unique to the process. The instability of GM lines is hardly addressed. We are told (p54) that in studies carried out largely by biotech companies there were no significant deviations from Mendelian ratios, but to infer stability from this is to make an elementary error in both statistics and genetics.

2. GM greatly increases the scope of horizontal gene transfer and recombination, which pose the most insidious dangers.

The genetic material of any and every species on earth can be recombined and transferred in the laboratory, even DNA from species that have been extinct for 400 000 years. There is no evolutionary precedent for this situation. New genes and new combinations can be introduced into our environment and food chain that have never existed. This important issue too, is not addressed in the GM Science Report.

3. GM DNA is definitely not the same as non-GM or natural DNA.

The claim is made repeatedly in the Report (pp.11, 90 and elsewhere) that GM DNA is no different from natural or non-GM DNA. This is simply not true. Many GM DNAs are combinations of genes and genetic material that have never existed, and would never have come into being but for genetic engineering in the laboratory. For example, promoters (genetic signals for boosting gene expression) from plant viruses are frequently joined to genes from bacteria and other species, and synthetic DNA sequences are often incorporated into GM DNAs.

More importantly, GM DNA is often designed to cross species barriers and to invade genomes, i.e., to enhance horizontal gene transfer and recombination, the very process that creates new disease agents and spreads antibiotic and drug resistance, and could trigger cancer in the event of integrating into the genome of mammalian cells.

The risk of creating disease agents and spreading antibiotic resistance is further increased by the fact that GM DNAs are predominantly from bacteria and viruses that cause diseases, and antibiotic resistance marker genes are a routine tool of the trade, and frequently remain in GM crops released into the environment.

That antibiotic resistance is already common (p.12) is no justification for using antibiotic resistance marker genes. Millions of hectares of GM crops with antibiotic resistance genes are bound to exacerbate existing problems of antibiotic resistance in deadly pathogens. The proposed methods of removing them with 'site-specific' recombination tools (p.97) have to be evaluated most carefully, as some, like the Cre-Lox and similar systems from bacteria, are already known to scramble genomes.

GM DNA is known to be structurally unstable from the beginning of genetic engineering, i.e., it has a tendency to fragment, and can disintegrate from the genome, which is one reason why GM lines are unstable. (The other reason is that the host cell can silence the transgene by chemical modification of its promoter.) This instability leads to genetic rearrangement in the host genome, changing the GM line in unpredictable ways, and also increases the likelihood that the GM DNA can transfer horizontally and recombine in part or in whole.

4. Many GM DNAs possess 'recombination hotspots' making them extra-unstable, and hence extra-prone to horizontal gene transfer and recombination, with all the attendant risks.

Recombination hotspots in GM DNA include sequences such as the left and right borders of integrating viruses and plasmids, artificial 'polylinkers' containing multiple restriction sites, and genetic signals such as the origin of replication, and, in the case of transferable plasmids, the origin of transfer.

One prominent example is the isolated cauliflower mosaic virus (CaMV) 35S promoter, widely incorporated into GM crops before its unsafe properties became known. It not only possesses a recombination hotspot, but is also promiscuously active in making genes over-express in species across the living world, including human cells. The GM Science Review Report continues to suppress this and other damning evidence, as before, by giving the totally unjustified impression that the CaMV 35S promoter is just the same as the virus itself or its genome, which we are said to have eaten for millennia without harm (p.70), and by omitting to cite two further key scientific publications from ISIS, which we have drawn attention to more than once. By way of refuting our concerns that the CaMV 35S promoter is unsafe, the Report even cites a submission from Roger Morton, noted more for his ad hominem attacks than his scientific credentials, and who is behind a recent attempt to discredit me on the eve of the launch of the Independent Science Panel on GM (see "Genetically modifying science", this series).

5. Direct evidence of hazards inherent to the technology is swept aside and misrepresented.

Topping the list of the direct evidence of hazard inherent to the technology is the study of Pusztai and co-workers, who found dramatic 'growth-factor like' effects in the stomach and intestinal lining of young rats fed GM potato for just 10 days, which were not present either in rats fed non-GM potatoes or in rats fed non-GM potatoes spiked with the transgene product. It suggested that the effects were due to the GM process or the GM construct, which happens to contain the CaMV 35S promoter. This raises a host of key questions. For example, had the CaMV 35S promoter transferred into the genome of cells lining the gut? If so, did it land near a growth factor gene to boost its expression? Could the over-expression of the growth factor gene be responsible for the overgrowth of the gut lining? Could this overgrowth be a prelude to cancer?

To refute this work, the GM Science Review Report cites the Scottish Executive's bald statement that the work was "fundamentally flawed", and claimed, "subsequent work has failed to substantiate the findings" referenced to Derek Burke's submission (p.66). Derek Burke has never carried out experiments to substantiate or refute the findings, nor has anyone else. If the findings have not been confirmed by subsequent work that is because no such work has ever been attempted.

Thereafter, Monsanto's feeding studies are liberally cited as evidence of "no harm" (p.68). Those studies carry as much weight as the repeatedly cited 'evidence' that (p.105 and elsewhere), "many hundreds of millions of people" have been eating GM foods or GM-fed animals "for up to seven years with no substantiated adverse effects reported." That latter 'experiment', carried out on hundreds of millions of people who never gave their informed consent, could not have revealed any but the most immediately obvious harmful effects, as there was no control group, and no systematic health monitoring. The Report omitted to mention, however, that scientists at the Centers for Disease Control in the United States found that between 1994, when GM food was first introduced, and 1999, foodborne illnesses in the United States have increased two to ten-fold [1]. The precise causes of the diseases are still largely unknown. Nevertheless, that, at least, is a peer-reviewed scientific publication, as opposed to pure speculation that there have been no adverse effects from eating GM foods.

6. Positive evidence of horizontal gene transfer denied and dismissed as "very rare".

It is remarkable that there has been only one single field monitoring experiment after millions of hectares of GM crops have been planted, and just one human feeding trial involving 19 individuals fed a single meal containing GM soya flour. Despite that, positive evidence of horizontal transfer of GM DNA to bacteria in the soil and in the human gut has been found. More remarkable still, our Government's science advisors persist in denying and dismissing this evidence. And in the case of the human feeding trial, there is no plan to carry out longer-term studies. Page 90 of the Report contains a statement that directly conflicts with existing evidence: "Trans-kingdom transfer of transgenic DNA from GM plant material to bacteria is unlikely to occur due to a series of well-established barriers and this is supported by experimental evidence."

One main excuse for denial is that the bacteria that have taken up the DNA cannot be isolated as cultures (p.96), even though molecular probes and selection by marker trait both indicated that horizontal gene transfer had occurred. This is either a remarkable example of ignorance or a deliberate attempt to mislead. It is generally accepted that less than 1% of the bacteria in the environment can be isolated by current culture methods. The failure to isolate the bacterial culture, therefore, can in no way be construed as evidence that horizontal gene transfer did not happen.

Not only that, several of the papers cited in the Report itself (pp 90-92) actually provided further evidence of horizontal gene transfer, which the Report fails to make fully explicit. For example, Duggens and coworkers (2003) found that the entire coding sequence of the Cry1A(b) transgene could still be detected in sheep rumen fluid 5 hours after feeding GM maize grains, and fragments more than 200bp long were detected 24 hours later. Plasmid containing the transgene and kanamycin resistance marker gene could still transfer the entire transgene as well as kanamycin resistance to E. coli after being kept for 5 minutes in the sheep's mouth. The authors remarked, "DNA released from feed material within the mouth has potential to transform naturally competent oral bacteria." Similarly, Mercer and coworkers (2001) showed that both plasmid and chromosomal DNA fragments were incompletely degraded after incubation in the human mouth, and can still transform Streptococcus gordonii, which normally lives in the mouth.

In fact, horizontal gene transfer could occur during food processing, long before the food is consumed, for most food processing fails to break down DNA appreciably.

A study on DNA stability in plant tissues (Chiter et al, 2000) showed that fresh maize and maize silage contained high molecular weight DNA that required relatively high temperatures and pressurised steam, or chemical expulsion and extrusion (in the case of oilseeds) to fully degrade. The authors commented, "These results imply that stringent conditions are needed in the processing of GM plant tissue for feedstuffs to eliminate the possibility of transmission of transgenes."

Straub and coworkers (1999) found that GM DNA of Lactobacillus in heat-treated fermented sausage could still be detected after 9 months of storage. Furthermore, the meat matrix protected DNA from degradation.

A paper not cited in the GM Science Report gave clear evidence of horizontal gene transfer in food. Bauer and coworkers [2] investigated the ability of a plasmid to transform Escherichia coli in 12 foods under conditions commonly found in processing and storage. Transformation was found in all foods with frequencies depending on the food and on temperature. Surprisingly, E. coli became transformed at temperatures below 5 degrees C, i.e. under conditions of storage of perishable foods. In soy drink this condition resulted in frequencies higher than those at 37 degrees C.

ISIS rejects GM Science Review Report
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The GM Science Review has failed to answer the charge that GM technology is inherently unsafe and unpredictable. The ISP rejects the conclusion that there is "no evidence" that GM crops pose a threat to health and the environment, and the recommendation to effectively commercialise GM crops on a "case by case" basis.

There is no case for growing any GM crops in Britain (or anywhere else in the world). On the contrary, when all the creditable scientific evidence and concerns are accurately taken into account, there are many reasons to ban the environmental release of GM crops to make way for organic farming, agroecology and other forms of non-GM sustainable agriculture.

(Note: The Independent Science Panel (ISP) also rejects the GM Science Review. Its full report will be posted on the ISP website
http://www.indsp.org/ at a later date.)

1. Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C. Griffin PM and Tauxe RV. Food-related illness and death in the United States. Emerging Infectious Diseases 1999, 5, 607-25.

2. Bauer F, Hertel C, Hammes WP. Transformation of Escherichia coli in foodstuffs. Syst Appl Microbiol. 1999, 22, 161-8.

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